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08 January 2025, Volume 29 Issue 1 Previous Issue    Next Issue

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Oral Herombopag Olamine and subcutaneous recombinant human thrombopoietin after haploidentical hematopoietic stem cell transplantation Kong Dai, Wang Xinkai, Zhang Wenhui, Pei Xiaohang, Lian Cheng, Niu Xiaona, Guo Honggang, Niu Junwei, Zhu Zunmin, Liu Zhongwen 2025, 29 (1):  1-7.  doi: 10.12307/2024.733 Abstract ( 27 )   PDF (886KB) ( 3 )   Save BACKGROUND: Allogeneic hematopoietic stem cell transplantation is an important treatment for malignant hematological diseases, and delayed postoperative platelet implantation is a common complication that seriously affects the quality of patient survival; however, there are no standard protocols to improve platelet implantation rates and prevent platelet implantation delays. OBJECTIVE: To compare the safety and efficacy of oral Herombopag Olamine versus subcutaneous recombinant human thrombopoietin for promoting platelet implantation in patients with malignant hematological diseases undergoing haploid hematopoietic stem cell transplantation. METHODS: Clinical data of 163 patients with malignant hematological diseases who underwent haploidentical hematopoietic stem cell transplantation from January 2016 to October 2022 were retrospectively analyzed. A total of 72 patients who started to subcutaneously inject recombinant human thrombopoietin at +2 days were categorized into the recombinant human thrombopoietin group; a total of 27 patients who started to orally take Herombopag Olamine at +2 days were categorized into the Herombopag Olamine group; and 64 patients who did not apply Herombopag Olamine or recombinant human thrombopoietin were categorized into the blank control group. The implantation status, incidence of acute graft-versus-host disease of degree II-IV within 100 days, 1-year survival rate, 1-year recurrence rate, and safety were analyzed in the three groups. RESULTS AND CONCLUSION: (1) The average follow-up time was 52(12-87) months. The implantation time of neutrophils in the blank control group, recombinant human thrombopoietin group, and Herombopag Olamine group was (12.95±3.88) days, (14.04±3.71) days, and (13.89±2.74) days, respectively, with no statistically significant difference (P=0.352); the implantation time of platelets was (15.16±6.27) days, (17.67±6.52) days, and (17.00±4.75) days, with no statistically significant difference (P=0.287). (2) The complete platelet implantation rate on day 60 was 64.06%, 90.28%, and 92.59%, respectively, and the difference was statistically significant (P < 0.001). The subgroup analysis showed that the difference between the blank control group and the recombinant human thrombopoietin group was statistically significant (P < 0.001), and the difference between the blank control group and the Herombopag Olamine group was statistically significant (P=0.004). The difference was not statistically significant between the recombinant human thrombopoietin group and Herombopag Olamine group (P=0.535). (3) 100-day II-IV degree acute graft-versus-host disease incidence in the blank control group, recombinant human thrombopoietin group, and Herombopag Olamine group were 25.00%, 30.56%, and 25.93%, respectively, and the difference was not statistically significant (P=0.752). (4) The incidence of cytomegalovirus anemia, cytomegalovirus pneumonia, and hepatic function injury had no statistical difference among the three groups (P > 0.05). (5) During the follow-up period, there was no thrombotic event in any of the three groups of patients. (6) The results showed that recombinant human thrombopoietin and Herombopag Olamine could improve the platelet implantation rate of malignant hematological disease patients after haploidentical hematopoietic stem cell transplantation, with comparable efficacy and good safety. Figures and Tables | References | Related Articles | Metrics

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Effect of Wenshen Tongluo Zhitong formula on mouse H-type bone microvascular endothelial cell/bone marrow mesenchymal stem cell co-culture system Zhou Shijie, Li Muzhe, Yun Li, Zhang Tianchi, Niu Yuanyuan, Zhu Yihua, Zhou Qinfeng, Guo Yang, Ma Yong, Wang Lining 2025, 29 (1):  8-15.  doi: 10.12307/2024.734 Abstract ( 22 )   PDF (1689KB) ( 3 )   Save BACKGROUND: Bone relies on the close connection between blood vessels and bone cells to maintain its integrity. Bones are in a physiologically hypoxic environment. Therefore, the study of angiogenesis and osteogenesis in hypoxic environment is closer to the microenvironment in vivo.  OBJECTIVE: To explore the influence of Wenshen Tongluo Zhitong (WSTLZT) formula on H-type bone microvascular endothelial cell/bone marrow mesenchymal stem cell co-culture system in hypoxia environment and its related mechanism.  METHODS: Enzyme digestion method and flow sorting technique were used to isolate and identify H-type bone microvascular endothelial cells. Mouse bone marrow mesenchymal stem cells were isolated and obtained by bone marrow adhesion method. H-type bone microvascular endothelial cell/bone marrow mesenchymal stem cell hypoxic co-culture system was established using Transwell chamber and anoxic culture workstation. WSTLZT formula powder was used to intervene in each group at a mass concentration of 50 and 100 μg/mL. The angiogenic function of H-type bone microvascular endothelial cells in the co-culture system was evaluated by scratch migration test and tube formation test. The osteogenic differentiation ability of bone marrow mesenchymal stem cells in the cocultured system was evaluated by alkaline phosphatase staining and alizarin red staining. The protein and mRNA expression changes of PDGF/PI3K/AKT signal axis related molecules in H-type bone microvascular endothelial cells in the co-cultured system were detected by Western Blotting and q-PCR, respectively.  RESULTS AND CONCLUSION: (1) Compared with the normal oxygen group, the scratch mobility and new blood vessel length of H-type bone microvascular endothelial cells were significantly higher (P < 0.05); the osteogenic differentiation capacity of bone marrow mesenchymal stem cells was higher (P < 0.05); the expression of PDGF/PI3K/AKT axis-related molecular protein and mRNA increased (P < 0.05) in the hypoxia group. (2) Compared with the hypoxia group, scratch mobility and new blood vessel length were significantly increased in the H-type bone microvascular endothelial cells (P < 0.05); bone marrow mesenchymal stem cells had stronger osteogenic function (P < 0.05); the expression of PDGF/PI3K/AKT axis-related molecular proteins and mRNA further increased (P < 0.05) after treatment with different dose concentrations of WSTLZT formula. These findings conclude that H-type angiogenesis and osteogenesis under hypoxia may be related to the PDGF/PI3K/AKT signaling axis, and WSTLZT formula may promote H-type vasculo-dependent bone formation by activating the PDGF/PI3K/AKT signaling axis, thereby preventing and treating osteoporosis. Figures and Tables | References | Related Articles | Metrics

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Restoration of osteogenic differentiation of bone marrow mesenchymal stem cells in mice inhibited by cyclophosphamide with psoralen Wang Chenglong , Yang Zhilie , Chang Junli , Zhao Yongjian , Zhao Dongfeng , Dai Weiwei , Wu Hongjin , Zhang Jie , Wang Libo , Xie Ying , Tang Dezhi , Wang Yongjun , Yang Yanping 2025, 29 (1):  16-23.  doi: 10.12307/2024.730 Abstract ( 20 )   PDF (1601KB) ( 3 )   Save BACKGROUND: Psoralen has a strong anti-osteoporotic activity and may have a restorative effect on chemotherapy-induced osteoporosis.  OBJECTIVE: To explore the restorative effect of psoralen on the osteogenic differentiation of bone marrow mesenchymal stem cells in mice inhibited by cyclophosphamide and its mechanism.  METHODS: C57BL/6 mouse bone marrow mesenchymal stem cells were isolated and cultured. Effect of psoralen on viability of bone marrow mesenchymal stem cells was detected by MTT assay. Osteogenic induction combined with alkaline phosphatase staining was used to determine the optimal dose of psoralen to restore the osteogenic differentiation of bone marrow mesenchymal stem cells inhibited by cyclophosphamide. The mRNA expression levels of Runx2, alkaline phosphatase, Osteocalcin, osteoprotegerin, and Wnt/β-catenin signaling pathway-related genes Wnt1, Wnt4, Wnt10b, β-catenin, and c-MYC were measured by RT-qPCR at different time points under the intervention with psoralen. The protein expression of osteogenic specific transcription factor Runx2 and Wnt/β-catenin signaling pathway related genes Active β-catenin, DKK1, c-MYC, and Cyclin D1 was determined by western blot assay at different time points under the intervention with psoralen.  RESULTS AND CONCLUSION: (1) There was no significant effect of different concentrations of psoralen on the viability of bone marrow mesenchymal stem cells. The best recovery of the inhibition of osteogenic differentiation of bone marrow mesenchymal stem cells caused by cyclophosphamide was under the intervention of psoralen at a concentration of 200 μmol/L. (2) Psoralen reversed the reduction in osteogenic differentiation marker genes Runx2, alkaline phosphatase, Osteocalcin and osteoprotegerin mRNA expression and Runx2 protein expression in bone marrow mesenchymal stem cells caused by cyclophosphamide conditioned medium. (3) Psoralen reversed the decrease in Wnt/β-catenin pathway-related genes Wnt4, β-catenin, c-MYC mRNA and Active β-catenin, c-MYC, and Cyclin D1 protein expression and the increase in DKK1 protein expression in bone marrow mesenchymal stem cells caused by cyclophosphamide conditioned medium. (4) The results showed that cyclophosphamide inhibited osteogenic differentiation of bone marrow mesenchymal stem cells in mice, and psoralen had a restorative effect on it. The best intervention effect was achieved at a concentration of 200 μmol/L psoralen, and this protective effect might be related to the activation of Wnt4/β-catenin signaling pathway by psoralen. Figures and Tables | References | Related Articles | Metrics

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Lnx1 expression in cortical neurons of rats with traumatic brain injury and mechanisms involved in secondary brain injury Ma Yanxia , Yang Yanwei , Ma Yuhang , Li Di , Wang Xiaoyan , Zou Mingming , Wei Shanwen 2025, 29 (1):  24-30.  doi: 10.12307/2024.735 Abstract ( 18 )   PDF (1621KB) ( 7 )   Save BACKGROUND: Apoptosis plays an important role in secondary brain injury. Therefore, to explore the pathophysiological mechanism of promoting nerve cell survival after traumatic brain injury provides a new direction and theoretical basis for the prevention and treatment of traumatic brain injury.  OBJECTIVE: To explore the expression changes of Lnx1 molecule in mammalian cortical neurons after brain injury and the possible mechanism involved in secondary brain injury.  METHODS: Eighty adult SD rats were divided into 20 male and 20 female mice in sham operation group and 20 male and 20 female mice in traumatic brain injury group. The traumatic brain injury rat model was established by heavy falling method. At 6, 12, 24, 48, and 72 hours after brain injury, the expression of related molecules in damaged cortical neurons was analyzed by RT-qPCR, western blot assay, and immunofluorescence staining.  RESULTS AND CONCLUSION: (1) The brain tissue of traumatic brain injury group was bleeding and obvious tissue injury could be observed. Water content of brain tissue increased after traumatic brain injury. (2) Compared with the sham operation group, the expression of Lnx1 in cortical neurons after traumatic brain injury increased significantly at 24 hours after injury. (3) After traumatic brain injury, the expression of PBK and BCR protein decreased, and the prosurvival factor ctgf increased. (4) These findings suggest that after traumatic brain injury, the expression of Lnx1 is up-regulated in neurons, which may be due to the decrease of the expression of its target molecules PBK and BCR, and further promote the expression of living factor ctgf, which has a protective effect on the damaged neurons. Figures and Tables | References | Related Articles | Metrics

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Adipose mesenchymal stem cell-derived exosome attenuates radiation-induced oral mucositis Li Yang, Fu Lili, Yang Jiantang 2025, 29 (1):  31-37.  doi: 10.12307/2025.040 Abstract ( 31 )   PDF (1268KB) ( 8 )   Save BACKGROUND: Radiotherapy for head and neck tumors is very likely to cause radiation-induced oral mucositis, which seriously affects the health of patients and the treatment plan of tumors. Mesenchymal stem cells have shown therapeutic potential in many diseases, and exosomes are one of the important factors for their function. At present, there is no application of adipose mesenchymal stem cell-derived exosomes in the study of radiation-induced oral mucositis.  OBJECTIVE: To investigate the role of adipose mesenchymal stem cell-derived exosomes in radiation-induced oral mucositis.  METHODS: Adipose mesenchymal stem cells and adipose mesenchymal stem cell-derived exosomes were extracted and identified. In vitro model of radiationinduced oral mucositis was induced by radiating oral mucosal epithelial cells with 3 Gy X-ray. Adipose mesenchymal stem cells or adipose mesenchymal stem cell-derived exosomes were pretreated for 48 hours before modeling. The proliferation capacity of oral mucosal epithelial cells was detected by EdU assay and clonal formation assay. A mouse model of radiation-induced oral mucositis was constructed through 3 Gy X-ray radiation. Adipose mesenchymal stem cells and adipose mesenchymal stem cell-derived exosomes were injected into the tail vein of radiation-induced oral mucositis mice. Hematoxylin-eosin staining and immunohistochemistry were used to evaluate the inflammatory changes of oral mucosal epithelial tissue.  RESULTS AND CONCLUSION: (1) Compared with the control group, both adipose mesenchymal stem cells and adipose mesenchymal stem cell-derived exosomes promoted the formation of oral epithelial cell clones and increased the positive rate of EdU in oral epithelial cells. (2) Both adipose mesenchymal stem cells and adipose mesenchymal stem cell-derived exosomes alleviated the inflammation of oral mucosal epithelium of irradiated mice; CD45 positive cells decreased and PCNA positive cells increased in oral mucosal epithelium. It is concluded that adipose mesenchymal stem cell-derived exosomes promote the proliferation of oral mucosal epithelial cells and release oral mucosal inflammation in mice with radiation-induced oral mucositis.  Figures and Tables | References | Related Articles | Metrics

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Luteolin improves myocardial cell death induced by serum from rats with spinal cord injury Zhang Wenwen , Xu Mengru , Tian Yuan , Zhang Lifei , Shi Shu , Wang Ning , Yuan Yuan , Wang Li , Hao Haihu 2025, 29 (1):  38-43.  doi: 10.12307/2024.729 Abstract ( 18 )   PDF (944KB) ( 7 )   Save BACKGROUND: Cardiac dysfunction due to spinal cord injury is an important factor of death in patients with spinal cord injury; however, the specific mechanism is still not clear. Therefore, revealing the mechanism of cardiac dysfunction in spinal cord injury patients is of great significance to improve their quality of life and survival rate. OBJECTIVE: To investigate the mechanism of luteolin in improving serum-induced myocardial cell death in spinal cord injury rats.  METHODS: Allen’s impact instrument was used to damage the spine T9-T11 of male SD rats to establish a spinal cord injury model meanwhile a sham operation group was set as the control group. The serum of rats of each group was collected. H9c2 cells were divided into a blank control group, a sham operated rat serum group, a spinal cord injury rat serum group and a luteolin pretreatment group. The cells in blank control group were only cultured with ordinary culture medium. The cells in the sham operated rat serum group were treated with medium containing 10% serum from sham operated rat. The cells in the spinal cord injury rat serum group were treated with medium containing 10% serum from spinal cord injury rat. The cells in the luteolin pretreatment group were precultured with a final concentration of 20 μmol/L luteolin for 4 hours and then changed to a medium containing 10% rat serum from spinal cord injury rat. After 24 hours of culture, the survival rate of each group of H9c2 cells was measured by CCK-8 assay. Western blot assay was used to detect the expression of autophagy related protein LC3 and p62 in H9c2 cells in each group.  RESULTS AND CONCLUSION: Compared with the blank control group, there was no significant change in cell survival rate in the sham operated rat serum group (P > 0.05). Compared with the sham operated rat serum group, the cell survival rate (P < 0.01) and the expression of LC3 protein (P < 0.05) in spinal cord injury rat serum group was significantly reduced, and the expression of p62 protein was significantly increased (P < 0.05). Compared with the spinal cord injury rat serum group, the survival rate of cells in the luteolin pretreatment group significantly increased (P < 0.000 1); the expression of LC3 protein significantly increased (P < 0.05), and the expression of p62 protein significantly decreased (P < 0.05). The results indicate that luteolin may improve myocardial cell death induced by serum from rats with spinal cord injury by promoting autophagy. Figures and Tables | References | Related Articles | Metrics

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Mechanism by which Angelica sinensis polysaccharide regulates bone marrow hematopoietic microenvironment for aplastic anemia Fu Jiaqi, Chen Xiubao, Cui Xing, Chen Zetao 2025, 29 (1):  44-51.  doi: 10.12307/2024.739 Abstract ( 18 )   PDF (3602KB) ( 3 )   Save BACKGROUND: How to improve the hematopoietic microenvironment is a hot topic in the treatment of aplastic anemia. OBJECTIVE: To explore the action mechanism of Angelica sinensis polysaccharide in the treatment of aplastic anemia by combining GEO sequencing analysis, network pharmacology, and experimental validation. METHODS: Aplastic anemia-related differentially expressed genes were obtained from GEO database, and gene ontology and gene set enrichment analysis were performed. The active components and targets of Angelica sinensis polysaccharide were obtained by combining the literature with PubChem, SwissTargetPrediction, and PharmMapper databases. After the intersection targets were taken, STRING and Cytoscape were used to construct protein-protein interaction network, and gene ontology and Kyoto encyclopedia of genes and genomes enrichment analysis was performed. Mouse model of aplastic anemia was established, and the effect and action mechanism of Angelica sinensis polysaccharide on aplastic anemia were verified by blood cell analyzer, flow cytometry, ELISA, immunohistochemistry, immunofluorescence, and western blot assay. RESULTS AND CONCLUSION: (1) A total of 834 differentially expressed genes were screened, which were involved in biological processes such as cell development, hematopoiesis, and myeloid cell differentiation. (2) 347 targets related to Angelica sinensis polysaccharide were retrieved and 77 potential therapeutic genes were screened. Among them, the degree values of angiogenic, apoptotic, and immune-related factors such as VEGFA, EGLN1, Bcl-2, interferon-γ, interleukin-2, interleukin-4, and interleukin-6 were significant. (3) KEGG pathway enrichment analysis revealed that the therapeutic targets were mainly enriched in Th17 cell differentiation, NK-related cytotoxicity, cell adhesion factors such as interferon-γ, interleukin-2, and interleukin-4 related signaling pathways. (4) Animal experiments showed that Angelica sinensis polysaccharide significantly improved bone marrow haematopoiesis, increased peripheral blood cell, and bone marrow single nucleated cell counts, and improved the survival rate of mice. Compared with the model group, mice in the Angelica sinensis polysaccharide group showed a significant decrease in the ratio of Th1/Th2 cells (P < 0.01), a decrease in the expression level of interferon-γ (P < 0.01), an increase in the level of interleukin-4 (P < 0.05), a significant increase in the level of VEGFA (P < 0.01), a significant decrease in EGLN1 (P < 0.01), a significant decrease in apoptosis rate of bone marrow single nucleated cells and reactive oxygen species level (P < 0.01), and a significant increase in cleaved Caspase-3 protein expression (P < 0.01), and a significant decrease in Bcl-2/Bax ratio (P < 0.01). (5) These findings show that Angelica sinensis polysaccharide can improve hematopoiesis of aplastic anemia mice by regulating aberrant T-cell subsets and promoting angiogenesis to improve hematopoietic microenvironment, and inhibiting apoptosis of bone marrow mononuclear cells.  Figures and Tables | References | Related Articles | Metrics

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Baicalein mitigates ferroptosis of neurons after subarachnoid hemorrhage Zhu Ting, Yue Tingting, Cui Yue, Lu Yue, Li Wei, Hang Chunhua 2025, 29 (1):  52-57.  doi: 10.12307/2024.731 Abstract ( 18 )   PDF (897KB) ( 3 )   Save BACKGROUND: Ferroptosis is a mode of programmed cell death distinct from apoptosis, necrosis, and other novel cellular deaths, which occurs mainly due to accumulated lipid peroxidation. Ferroptosis has been shown to be involved in the pathological process following subarachnoid hemorrhage. Baicalein, serving as an adept sequestered of iron, evinces its prowess by quelling lipid peroxidative cascades. Nonetheless, the enigma lingers as to whether baicalein possesses the capacity to ameliorate neuronal ferroptosis, elicited in the wake of early brain injury after subarachnoid hemorrhage. OBJECTIVE: To investigate the effect and mechanism of baicalein on neuronal ferroptosis after subarachnoid hemorrhage. METHODS: Primary neuronal cells were extracted from C57BL/6L fetal mice at 16-17 days of gestation. Hemoglobin was used to stimulate primary neuronal cells to simulate an in vitro subarachnoid hemorrhage model. The viability of primary neuronal cells treated with baicalein at concentrations of 5, 15, 25, 50, and 100 μmol/L for 24 hours was detected by CCK-8 assay to determine the optimal concentration of baicalein. Primary neuronal cells were divided into control group, hemoglobin group, and hemoglobin+baicalein group. The levels of reactive oxygen species and malondialdehyde in cells were detected by kits. The mRNA expressions of ferroptosis-related markers PTGS2, SLC7A11, and glutathione peroxidase 4 were detected by RT-PCR. The primary neuronal cells were further divided into control group, SLC7A11 inhibitor Erastin group, hemoglobin group, hemoglobin+baicalein group, and hemoglobin+baicalein+Erastin group. The expression of the ferroptosis related markers SLC7A11 and glutathione peroxidase 4 was detected by western blot assay.  RESULTS AND CONCLUSION: (1) Baicalein (25 μmol/L) was selected as the following experimental concentration. (2) Compared with the hemoglobin group, the level of malondialdehyde and the level of reactive oxygen species were significantly decreased (P < 0.05) in the hemoglobin+baicalein group. (3) Compared with the hemoglobin group, the mRNA expression of PTGS2 significantly decreased, and the mRNA expression of SLC7A11 and glutathione peroxidase 4 significantly increased (P < 0.000 1) in the hemoglobin+baicalein group. (4) SLC7A11 inhibitor Erastin could reverse the baicalin-improved ferroptosis effect to a certain extent (P < 0.05). (5) The results showed that baicalein could alleviate the ferroptosis of neuronal cells after subarachnoid hemorrhage through the SLC7A11/GPX4 pathway. Figures and Tables | References | Related Articles | Metrics

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Anthocyanins from Lycium ruthenicum Murr combined with human adipose-derived pericytes/perivascular cells support proliferation of umbilical cord blood hematopoietic stem/progenitor cells Shen Yamei, Niu Yunxia, Yang Tingting, Ma Jie, Hu Daihong, Zheng Bo 2025, 29 (1):  58-64.  doi: 10.12307/2024.738 Abstract ( 23 )   PDF (2454KB) ( 3 )   Save BACKGROUND: Anthocyanin is one of the most important active components in Lycium ruthenicum Murr, which has antioxidant and immunomodulatory effects. CD146+ human adipose-derived pericytes/perivascular cells (CD146+hAD-PCs) are the progenitors of bone marrow mesenchymal stem cells, which can promote the proliferation and differentiation of hematopoietic stem/progenitor cells in vitro. The support effect of anthocyanin in combination with CD146+hAD-PCs on umbilical cord blood hematopoietic stem/progenitor cells remains to be studied. OBJECTIVE: To investigate the supporting effect of anthocyanins in Lycium ruthenicum Murr (ALRM) combined with CD146+hAD-PCs on umbilical cord blood CD34+hematopoietic stem/progenitor cells (UCB CD34+HSPCs) in vitro. METHODS: The CCK-8 assay was used to detect the effect of different concentrations (0, 200, 400, 600, 800, 1 000 mg/L) of ALRM on the proliferation of CD146+hAD-PCs. Flow cytometry was used to detect the effect of ALRM on the cell cycle of CD146+hAD-PCs. The co-culture experiments were divided into blank group, ALRM group, CD146+hAD-PCs group, and ALRM+CD146+hAD-PCs group to analyze the in vitro supporting effect of ALRM combined with CD146+hAD-PCs on UCB CD34+HSPCs. The number of expanded cells and the number of colony-forming units were compared at 1, 2, and 4 weeks of co-culture. The immunophenotype of cells was detected by flow cytometry. The level of cytokines was detected by enzyme-linked immunosorbent assay.   RESULTS AND CONCLUSION: (1) The cell viability of CD146+hAD-PCs was highest at an ALRM concentration of 200 mg/L, the proportion of G0/G1 phase cells decreased and the proportion of S and G2/M phase cells increased in CD146+hAD-PCs (P < 0.01). (2) The change in number of UCB CD34+HSPCs cells in the ALRM+CD146+hAD-PCs group was higher than that in the ALRM group at 1, 2, and 4 weeks of co-culture (all P < 0.05), and higher than that in CD146+hAD-PCs group at 2 and 4 weeks of co-culture (all P < 0.05). The number of cells in the ALRM group and blank group decreased gradually with the extension of co-culture time. (3) Colony forming capacity and immunophenotype analysis: The number of colony-forming units in the ALRM+CD146+hAD-PCs group was higher than that in the CD146+hAD-PCs group and ALRM group at 1 and 2 weeks of co-culture (P < 0.05). The proportion of CD45+ and CD34+CD33-cells in the ALRM+CD146+hAD-PCs group was higher than that in the CD146+hAD-PCs group at 1 and 2 weeks of co-culture (all P < 0.01). (4) Changes in cytokines: Interleukin-2 level in the ALRM+CD146+hAD-PCs group was higher than that in the ALRM and CD146+hAD-PCs groups (P < 0.05). The interleukin-3 content of the ALRM+CD146+hAD-PCs group was higher than that of the CD146+hAD-PCs group at 2 and 4 weeks (P < 0.05). The expression level of granulocyte colony-stimulating factor in the ALRM+CD146+hAD-PCs group was higher than that in the CD146+hAD-PCs group at 1 week, and higher than that in the ALRM group and CD146+hAD-PCs group at 2 weeks (P < 0.01). Interferon-γ content in the ALRM group and ALRM+CD146+hAD-PCs group was lower than that in the CD146+hAD-PCs group at 1, 2, and 4 weeks of co-culture (P < 0.01). (5) Due to the absence of stromal cells in the blank group, UCB CD34+HSPCs could not be counted after 1 week of co-culture and were not subjected to immunophenotyping, colony analysis, or cytokine assays. (6) In summary, ALRM can promote the expansion of UCB CD34+HSPCs in vitro by promoting CD146+hAD-PCs proliferation and cell cycle transformation, which is of great value in hematopoietic stem cell transplantation. Figures and Tables | References | Related Articles | Metrics

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Exercise preconditioning combined with bone marrow mesenchymal stem cell transplantation for myocardial infarction in rats Wang Zhikun, Bai Shaoxuan, Zhao Wei, Wang Chenyu 2025, 29 (1):  65-73.  doi: 10.12307/2024.736 Abstract ( 22 )   PDF (1713KB) ( 4 )   Save BACKGROUND: Stem cell therapy has broad prospects in improving cardiac remodeling after myocardial infarction; however, alteration in the myocardial microenvironment affects the therapeutic efficacy of stem cells. Exercise preconditioning is similar to ischemic preconditioning and can have a protective effect on the myocardium. However, little attention has been paid to the effects and mechanisms of the combined effects of exercise preconditioning and stem cell transplantation. OBJECTIVE: To observe the effect of exercise preconditioning on bone marrow mesenchymal stem cell transplantation in rats with myocardial infarction and to explore the mechanism of local inflammatory microenvironment. METHODS: Eighty female SD rats were randomly divided into sham operation group, model group, transplantation group, and combination group, with 20 rats in each group. The rat model of myocardial infarction was made by ligating the left anterior descending branch of coronary artery. The sham operation group was only threaded without ligature. The transplantation and combination groups were injected with bone marrow mesenchymal stem cells of male rats into the myocardium after modeling. In addition, the combination group also required 8 weeks of treadmill exercise (i.e., exercise preconditioning) before modeling. Four weeks after stem cell transplantation, exercise performance was measured by incremental exercise exhaustion test; cardiac structure and function were measured by echocardiography; left ventricular hemodynamics was measured by pressure-volume catheterization, and myocardial histopathology was observed by in situ staining and myocardial collagen volume fraction was obtained. Quantitative reverse transcription polymerase chain reaction was used to detect left ventricular pro-inflammatory factor (interleukin-1β, interleukin-6, tumor necrosis factor-α), anti-inflammatory factor (interleukin-10), sex-determining region of Y chromosome, and fetal genes (atrial natriuretic peptide, brain natriuretic peptide, β-myosin heavy chain) mRNA expression level at 1, 7 days and 4 weeks after stem cell transplantation. RESULTS AND CONCLUSION: (1) Four weeks after stem cell transplantation: compared with sham operation group, exercise performance, and left ventricular ejection fraction were reduced (P < 0.05); myocardial infarction area, cardiomyocyte cross-sectional area, and collagen volume fraction were increased (P < 0.05); the mRNA expression of fetal genes and pro-inflammatory factors were up-regulated (P < 0.05), and the mRNA expression of interleukin-10 was down-regulated (P < 0.05) in the model group. Compared with the model group, exercise performance and left ventricular ejection fraction were increased (P < 0.05); myocardial infarction area, cardiomyocyte cross-sectional area, and collagen volume fraction were decreased (P < 0.05); mRNA expression of fetal genes and pro-inflammatory factors was down-regulated (P < 0.05), and that of interleukin-10 had no significant change (P > 0.05) in the transplantation group. Compared with the transplantation group, all the above indicators in the combination group were further improved (P < 0.05). (2) One day and 7 days after stem cell transplantation, compared with the transplantation group, the mRNA expression of sex-determining region of Y chromosome in the combination group increased (P < 0.05). (3) Correlation analysis showed that interleukin-1β, interleukin-6 (except on the 1st day after transplantation), and tumor necrosis factor-α were negatively correlated with the mRNA expression of sex-determining region of Y chromosome (P < 0.05), while interleukin-10 was positively correlated with that of sex-determining region of Y chromosome (P < 0.05). These findings suggest that exercise preconditioning can enhance the effect of bone marrow mesenchymal stem cell transplantation in rats with myocardial infarction, which is characterized by suppression of cardiac remodeling and further amelioration of cardiac function. The mechanism is related to the improvement of the myocardial inflammatory microenvironment to promote bone marrow mesenchymal stem cell retention and survival. Figures and Tables | References | Related Articles | Metrics

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Osteogenic ability and autophagy level between normal and inflammatory periodontal ligament stem cells Mao Jiaqi, Zhao Liru, Yang Dongru, Hu Yongqing, Dai Bowen, Li Shujuan 2025, 29 (1):  74-79.  doi: 10.12307/2025.037 Abstract ( 19 )   PDF (2303KB) ( 4 )   Save BACKGROUND: Inflammation affects the osteogenic differentiation of periodontal ligament stem cells, and the osteogenic ability and autophagy level of periodontal ligament stem cells are closely related. However, there are no relevant reports on whether inflammation affects the osteogenic ability and autophagy level of periodontal ligament stem cells at different stages of osteogenic differentiation.   OBJECTIVE: To explore alkaline phosphatase expression and autophagy periodontal ligament stem cells levels in periodontitis and normal conditions.  METHODS: Periodontal ligament stem cells from normal and periodontitis patients were isolated and cultured, and underwent Vimentin, pan-CK, and Stro-1 fluorescence staining. At 3, 7, and 14 days of osteogenic differentiation, western blot assay was used to detect the protein expression levels of alkaline phosphatase, LC3B, Beclin1, and ATG5 in normal and inflammatory periodontal ligament stem cells. The mRNA expression levels of alkaline phosphatase, bone sialoprotein, osteocalcin, Runx2, LC3B, Beclin1, and ATG5 were detected by real-time PCR. RESULTS AND CONCLUSION: (1) Stro-1 was positive, Vimentin was positive, and pan CK was negative in periodontal ligament stem cells. (2) At 3, 7, and 14 days after osteogenic differentiation, compared with normal periodontal ligament stem cells, the mineralization nodules formed by periodontal ligament stem cells from inflammatory sources were significantly reduced (P < 0.01); the expression of alkaline phosphatase protein and mRNA was significantly lower (P < 0.05); the mRNA expression levels of bone sialoprotein, osteocalcin, and Runx2 were significantly decreased (P < 0.05). (3) At 7 and 14 days after osteogenic differentiation, compared with normal periodontal ligament stem cells, the expression levels of ATG5, LC3B, and Beclin1 proteins and mRNA of periodontal ligament stem cells were downregulated (P < 0.05). These findings suggest that inflammation reduces the activity of periodontal ligament stem cells in mineralizing nodule formation and the expression of alkaline phosphatase and weakens the autophagy potential of periodontal ligament stem cells at 7 and 14 days after osteogenic differentiation. Figures and Tables | References | Related Articles | Metrics

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Effect of ursolic acid on osteogenic differentiation of human periodontal ligament stem cells#br# Zheng Qian, Liu Pingping, Gu Yujie, Xie Lei 2025, 29 (1):  80-86.  doi: 10.12307/2025.031 Abstract ( 18 )   PDF (1069KB) ( 3 )   Save BACKGROUND: Ursolic acid can promote the directed differentiation of bone marrow mesenchymal stem cells into osteoblasts. However, there are few reports on whether ursolic acid has osteogenic effect on human periodontal ligament stem cells. OBJECTIVE: To investigate the effect of ursolic acid on proliferation and osteogenic differentiation of human periodontal ligament stem cells. METHODS: The human periodontal ligament stem cells were isolated and cultured. Passage 3 cells were selected and treated with ordinary medium containing different concentrations (0, 1, 2, 4, 6, 8 μmol/L) of ursolic acid. After intervention for 1, 3, 5, 7 days, the cell proliferation was detected by CCK-8 assay and the appropriate intervention concentration was screened. Passage 3 human periodontal ligament stem cells were treated with osteogenic induction solution containing 0, 1, 2, 4 μmol/L ursolic acid, respectively. After 7 days of intervention, the mRNA expressions of alkaline phosphatase, Runx2, and osteocalcin were detected by qRT-PCR. After 14 days of intervention, the formation of mineralized nodules was observed by alizarin red staining. Passage 3 human periodontal ligament stem cells were taken and the control group was added with osteogenic induction solution; the ursolic acid group and the antagonist group were added with osteogenic induction solution containing ursolic acid (2 μmol/L) and the bone morphogenetic protein signaling pathway antagonist Noggin, respectively. The ursolic acid+antagonist group was added with osteogenic induction solution containing ursolic acid (2 μmol/L) and Noggin, the inhibitor of bone morphogenetic protein signaling pathway, and cultured for 7 days. qRT-PCR and western blot assay were used to detect the mRNA and protein expressions of bone morphogenetic protein 2, Smad1, osteopontin, and Runx2. RESULTS AND CONCLUSION: (1) 1, 2, 4 μmol/L ursolic acid could promote the proliferation of human periodontal ligament stem cells. 6, 8 μmol/L ursolic acid could inhibit the proliferation of human periodontal ligament stem cells, and 1, 2, 4 μmol/L ursolic acid was selected to intervene in subsequent experiments. (2) Compared with 0 μmol/L, 1, 2, 4 μmol/L ursolic acid could promote the expression of alkaline phosphatase, Runx2, and osteocalcin mRNA and the formation of mineralized nodules (P < 0.05), and the effect of 2 μmol/L ursolic acid was the most significant. (3) Compared with the control group, the mRNA and protein expressions of bone morphogenetic protein 2, Smad1, osteopontin, and Runx2 in the ursolic acid group were increased (P < 0.05), while mRNA and protein expressions of the above indexes were decreased in the antagonist group (P < 0.05). Compared with the ursolic acid group, mRNA and protein expressions of above indexes were decreased in ursolic acid+antagonist group (P < 0.05). (4) The results indicate that ursolic acid promotes osteogenic differentiation of human periodontal ligament stem cells through bone morphogenetic protein signaling pathway.  Figures and Tables | References | Related Articles | Metrics

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A bibliometric analysis of non-coding RNA and mesenchymal stem cell research Zhou Jiaxin, Tao Jiang 2025, 29 (1):  87-94.  doi: 10.12307/2025.006 Abstract ( 16 )   PDF (1702KB) ( 9 )   Save BACKGROUND: Non-coding RNA, as a class of RNA molecules that do not encode proteins, plays a crucial role in cellular regulation. Simultaneously, mesenchymal stem cells possess multipotent differentiation capabilities, making them vital for tissue repair and regeneration. In recent years, researchers have extensively explored the role of non-coding RNA in regulating the functions of mesenchymal stem cells. OBJECTIVE: To systematically understand the trends and key areas of research related to non-coding RNA and mesenchymal stem cells through bibliometric analysis. METHODS: Literature data on non-coding RNA and mesenchymal stem cell-related research were retrieved from the Science Citation Index Expanded in the Web of Science Core Collection from 1990 to the present. The literature data were analyzed using bibliometric tools such as VOSviewer and CiteSpace, focusing on publication output, clustering, citation frequency, burstiness, and intermediary centrality with respect to years, countries or regions, research institutions, cited references, and keywords. This analysis aimed to reveal the knowledge base and emerging hotspots in the research field. RESULTS AND CONCLUSION: (1) This study included a total of 5 348 articles for analysis, showing a significant growth trend in relevant literature from 1997 to 2021. Although there was a slight decrease in 2022, the publication output remained at a high level. China dominated the research in this field, with Shanghai Jiao Tong University being the most active contributor. (2) Analysis of cited references revealed that highly bursty, intermediary, and cited articles were mainly related to topics such as microRNA, extracellular vesicles, and bone metabolism. These articles constitute an important knowledge base for research on non-coding RNA and mesenchymal stem cells. (3) Burstiness analysis of keywords identified persistent bursts in keywords such as exosomes, circular RNA, extracellular vesicles, and injury. (4) Cluster evolution analysis of keywords with continuous growth in publication output included clusters related to tumor microenvironment, osteoarthritis, oxidative stress, and extracellular vesicles. These keywords reflect the current and future research hotspots in the field. (5) The findings of this study not only illustrate the research trends in the field of non-coding RNA and mesenchymal stem cells but also provide potential directions and insights for researchers. Figures and Tables | References | Related Articles | Metrics

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Mechanism by which Huangqintang regulates intestinal flora for treatment of intestinal acute graft-versus-host disease in mice Xia Mengting, Sun Runjie, Fu Jiaqi, Li Suzhen, Yu Manya, Cui Xing 2025, 29 (1):  95-102.  doi: 10.12307/2024.727 Abstract ( 15 )   PDF (3619KB) ( 4 )   Save BACKGROUND: Intestinal acute graft-versus-host disease is one of the most aggressive complications after allogeneic hematopoietic stem cell transplantation with high lethality. How to improve intestinal inflammation and regulate autophagy by applying traditional Chinese medicine in order to treat intestinal acute graft-versus-host disease is a worthwhile research issue nowadays.  OBJECTIVE: To investigate the mechanism of Huangqintang modulating intestinal flora for the treatment of intestinal acute graft-versus-host disease.   METHODS: CB6F1 mice were irradiated with 60Co X radiation at a total dose of 8 Gy, and then single nucleated cell suspensions (bone marrow cells + splenocytes) from Balb/c H-2d mice were injected into the tail vein in order to prepare a model of intestinal acute graft-versus-host disease. These samples were randomly divided into the model group and the high-, moderate-, and low-dose Huangqintang groups. After modeling, the model, high-, moderate-, and low-dose groups received different doses of Huangqintang or an equal volume of saline by continuous gavage for 14 days. Clinical acute graft-versus-host disease grading, and survival time was recorded. Small intestinal tissues from each group were stained with hematoxylin and eosin for small intestinal mucosal pathology scoring. The intestinal flora of mice in each group was detected using 16S rDNA sequencing. Autophagy-related markers were detected using immunofluorescence, immunohistochemistry, and PCR.  RESULTS AND CONCLUSION: (1) Compared with the model group, the survival time of mice was significantly prolonged (P < 0.01); the clinical acute graft-versus-host disease scores were significantly reduced (P < 0.01); the pathological grading scores of the small intestinal mucosa were significantly diminished (P < 0.01); the levels of the small intestinal tissue inflammatory factors tumor necrosis factor-α, interleukin-1β, and interleukin-6, were significantly decreased (P < 0.01); the structural integrity of the small intestinal mucosal epithelium was partially restored in mice after the intervention of moderate and high-dose Huangqintang. (2) The study of intestinal flora found that compared with the model group, the pro-inflammatory strain Enterococcus was significantly reduced (P < 0.05), while beneficial bacteria such as Clostridium_innocuum and Rhodococcus, a pro-autophagy bacterium, were significantly elevated (P < 0.05) in the moderate-dose Huangqintang group. (3) Compared with the model group, the autophagy markers were significantly elevated in the moderate-dose Huangqintang group (P < 0.05); under transmission electron microscopy, the number of autophagic vacuoles of moderate-dose Huangqintang group increased significantly. (4) The results showed that Huangqintang significantly reduced the abundance of conditionally pathogenic bacteria and the level of inflammatory factors in small intestinal tissues, and increased the relative abundance of beneficial bacteria and promoted the expression of autophagy in the small intestinal mucosa, which resulted in a significant improvement of intestinal symptoms in mice with acute graft-versus-host disease.  Figures and Tables | References | Related Articles | Metrics

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Endothelial cell-specific bone morphogenetic protein 2 affects angiogenesis: bioinformatics analysis and experimental validation Yan Ru, Wang Kairu, Zhang Feiyan, Jia Shaobin, Cong Guangzhi 2025, 29 (1):  103-110.  doi: 10.12307/2024.737 Abstract ( 15 )   PDF (1623KB) ( 3 )   Save BACKGROUND: Angiogenesis is the main treatment target of cardiovascular diseases. Bone morphogenetic protein 2 can modulate angiogenesis, but the regulatory effect of endothelial cell-specific bone morphogenetic protein 2 on angiogenesis is unclear.  OBJECTIVE: To investigate the effect of endothelial-specific bone morphogenetic protein 2 on angiogenesis.  METHODS: (1) Bioinformatics analysis: Cellular expression specificity and abundance of bone morphogenetic protein 2 were meta-analyzed by the PanglaoDB single-cell transcriptome database. The endothelial cell transcriptome sequencing dataset of the mouse hindlimb model and endocardial transcriptome dataset of mice overexpressing bone morphogenetic protein 2 were reanalyzed to evaluate the effect of endothelial cell bone morphogenetic protein 2 on the angiogenesis pathway. (2) Validation in vivo: After establishing the mouse hindlimb model, we compared the blood perfusion between the affected and sham limb at 7, 14, and 21 days. The expression of the colocation of bone morphogenetic protein 2 and CD31 was explored by immunofluorescence and immunohistochemical staining. (3) Validation in vitro: The cultured human umbilical vein endothelial cells in vitro were divided into a control group, a hypoxia group, and a bone morphogenetic protein 2 inhibitor Noggin intervention group. After being cultured for 24 hours, the angiogenesis of endothelial cells in each group was observed.  RESULTS AND CONCLUSION: (1) Endothelial cells are an important cell subgroup expressing bone morphogenetic protein 2. Both in the mouse hindlimb ischemia model and endocardial cells overexpressing bone morphogenetic protein 2, bone morphogenetic protein 2 was significantly up-regulated, and the angiogenesis pathway was significantly activated. (2) In the mouse hindlimb model, bone morphogenetic protein 2-positive blood vessels around neoangiogenesis increased significantly at 7 days of ischemia (P < 0.05), and decreased significantly after 2 weeks of ischemia (P < 0.001). (3) In umbilical vein endothelial cells cultured in vitro, after hypoxic intervention, the migration and sprouting of endothelial cells increased significantly, and the expression of angiogenesis factors vascular endothelial growth factor and platelet-derived growth factor was significantly increased. Noggin significantly reduced hypoxia-induced endothelial cell angiogenesis (P < 0.001) and down-regulated the expression of vascular endothelial growth factor and platelet-derived growth factor (P < 0.01). (4) These findings verify that endothelial cell-specific bone morphogenetic protein 2 can regulate angiogenesis, and targeting endothelial cell bone morphogenetic protein 2 is a promising way to improve angiogenesis.   Figures and Tables | References | Related Articles | Metrics

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Reference threshold and offspring short-term security of in vitro fertilization-embryo transfer sperm DNA fragmentation index based on live birth Zhou Chao, Wang Shuxian, Yu Chunmei, Yu Guangyu, Jiang Yueyuan 2025, 29 (1):  111-119.  doi: 10.12307/2024.137 Abstract ( 32 )   PDF (1143KB) ( 3 )   Save BACKGROUND: There is a significant correlation between sperm DNA fragmentation index and fertilization, embryonic development potential, embryo implantation, miscarriage, and offspring safety. However, its clinical reference value is affected by many factors, resulting in extremely limited clinical significance. This study took live birth as the outcome, corrected other confounding factors through propensity score matching, constructed the best clinical cutoff value of sperm DNA fragmentation index and live birth, and conducted internal and external tests on it, which has good predictive value and clinical application efficiency. OBJECTIVE: To investigate the reference threshold and offspring short-term security of in vitro fertilization-embryo transfer sperm DNA fragmentation index based on live birth. METHODS: A total of 1 921 patients who received in vitro fertilization and embryo transfer in Changzhou Maternal and Child Health Area Hospital from May 2019 to May 2021 were selected. On the basis of tendency matching tolerance of 0.02 and propensity score matching of 1:1, 540 cases were successfully matched in each live birth group and non-live birth group, and the model group was established. 135 patients who received in vitro fertilization and embryo transfer in Nanxishan Hospital of Guangxi Zhuang Autonomous Region were selected as the external validation group. The optimal clinical cutoff value of sperm DNA fragmentation index for live birth was investigated by the receiver operating characteristic curve. The accuracy and clinical application efficacy of the cutoff value were evaluated by restricted cubic spline curve, standard curve, clinical decision curve, clinical impact curve and internal and external validation tests.  RESULTS AND CONCLUSION: (1) The DNA fragmentation index of sperm in the non-live birth group was significantly higher than that in the live birth group and had a significant negative correlation with live birth (r=-0.444, P < 0.001). (2) Receiver operating characteristic curve results showed that the optimal cut-off value of DNA fragmentation index for live birth was 24.33%; the area under the curve was 0.775(0.746, 0.804); the specificity was 72.60%; the sensitivity was 78.90%, and the accuracy was 75.70%. (3) Restricted cubic spline curve fitting the results of Logistic regression showed that when the sperm DNA fragmentation index was greater than 24.57%, the risk of clinical non-live birth increased. (4) The probability of Logistic regression analysis results showed that sperm DNA fragmentation index was a risk factor for live birth [OR(95%CI)=0.916(0.904, 0.928), P < 0.001], and when sperm DNA fragmentation index was greater than 27.78%, the probability of clinical live birth would be less than 50%. With the increase of sperm DNA fragmentation index by 1 unit, the probability of a live birth fell by 8.4%. (5) Internal and external to the validation of the clinical cutoff value showed that the cutoff point had certain clinical predictive value and accuracy. (6) Clinical decision curve and clinical impact curve results exhibited that the prediction model based on the clinical cut-off value had the maximum clinical net benefit value when the threshold probability was 0.22-0.73, and the ratio of loss to gain within the threshold probability range was always less than 1, which confirmed that the prediction model had good clinical application effectiveness. (7) The results of sperm DNA fragmentation index and offspring short-term security analysis showed that sperm DNA fragmentation index had no significant differences with preterm birth, body weight, deformity and sex. (8) These findings suggest that the optimal clinical cut-off value of sperm DNA fragmentation index for in vitro fertilization-embryo transfer live birth was 24.33%. The established clinical prediction model has good differentiation, accuracy and clinical application effectiveness. Sperm DNA fragmentation index has no significant impact on offspring short-term security, but large samples and long-term follow-up evaluation are still needed.  Figures and Tables | References | Related Articles | Metrics

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Application of stem cells in endothelialization of small-diameter blood vessel prosthesis Zheng Ankai, Liu Ruiming, Xiang Qiuling 2025, 29 (1):  120-127.  doi: 10.12307/2025.021 Abstract ( 16 )   PDF (1038KB) ( 8 )   Save BACKGROUND: The small-diameter blood vessel prosthesis faces the problem of lumen stenosis or even occlusion due to thrombogenesis and intimal hyperplasia after transplantation. The application of stem cells as seed cells to achieve endothelialization of blood vessel prosthesis helps to improve the long-term patency rate after vascular graft transplantation. OBJECTIVE: To summarize the research progress of the application of stem cells in the endothelialization of small-diameter blood vessel prosthesis. METHODS: The relevant articles published on PubMed and WanFang databases from 2013 to 2023 were retrieved by the first author. Chinese and English search terms included “vascular graft, tissue-engineered blood vessel/vascular tissue engineering, endothelialization, stem cells, endothelial progenitor cells, mesenchymal stem cells, induced pluripotent stem cells, embryonic stem cells.” The relative articles in the domestic and overseas about the application of stem cells in the endothelialization of small-diameter blood vessel prosthesis in the past 10 years were retrieved. A total of 552 articles were initially found and we finally selected 81 articles to review according to inclusion and exclusion criteria.  RESULTS AND CONCLUSION: (1) The low long-term patency rate restricts the application of small-diameter blood vessel prosthesis in clinic. The main causes of low long-term patency rate are thrombogenesis and intimal hyperplasia. The endothelium of native vessels has the function of anti-thrombogenesis and intimal hyperplasia. Endothelialization can simulate the function of native vessels, which is an effective way to improve long-term patency rate. (2) The small-diameter blood vessel prosthesis will undergo in vivo endothelialization after being implanted, but it is difficult to form complete endothelium. Stem cells have the potential to differentiate into endothelial cells. Recruiting stem cells in vivo or seeding them on the inner surface of blood vessel prosthesis in vitro is research strategy to achieve endothelialization. (3) The long-term patency rate of small-diameter blood vessel prosthesis has been improved to a certain extent through seeding endothelial progenitor cells, mesenchymal stem cells, induced pluripotent stem cells, and embryonic stem cells. Each has its own advantages. Endothelial progenitor cells are easy to obtain and can be directly used for seeding. Mesenchymal stem cells come from a wide range of sources and have the function of paracrine and immunological regulation. Induced pluripotent stem cells are rich in sources and the immunogenicity can be eliminated. Embryonic stem cells have a strong proliferative ability and can differentiate into many cells. (4) The application of stem cells in blood vessel prosthesis has not yet been transformed into clinic. Further researches are needed to promote clinical translation. Figures and Tables | References | Related Articles | Metrics

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Effect of bone marrow fat on bone metastasis and quantitative evaluation by magnetic resonance imaging Xie Qinglin, Zhang Xiaodong 2025, 29 (1):  128-135.  doi: 10.12307/2024.732 Abstract ( 16 )   PDF (907KB) ( 5 )   Save BACKGROUND: The accurate diagnosis of early bone metastases plays an important role in treatment and prognosis. Bone biopsy is the gold standard for the diagnosis of bone metastases, but it is difficult to implement in clinical practice because of its invasive and small specimen size. In recent years, with the continuous development of magnetic resonance imaging technology, quantitative magnetic resonance imaging techniques such as magnetic resonance spectroscopy and based on chemical shift encoded magnetic resonance imaging have been widely used in the diagnosis of bone metastasis. The derived markers include table signal fat fraction and proton density fat fraction. All of them could reflect the bone marrow fat content. At present, the role of bone marrow fat in the development of bone metastases has become a new focus of attention.  OBJECTIVE: To review the effect of bone marrow fat on bone metastasis and the quantitative evaluation techniques of magnetic resonance imaging, to summarize and compare the advantages and disadvantages of different magnetic resonance imaging fat quantification techniques in evaluating bone metastasis and their clinical applications.  METHODS: The computer was used to search relevant literature in PubMed and CNKI database. Chinese and English search terms were “bone metastases, bone marrow adipocytes, magnetic resonance imaging, quantitative MRI, fat fraction, magnetic resonance spectrum, chemical shift encoding-based water–fat imaging.” A total of 67 relevant articles were obtained according to the inclusion and exclusion criteria.  RESULTS AND CONCLUSION: (1) Bone marrow adipocytes can contribute to the occurrence of bone metastasis by secreting a variety of related hormones and cytokines, providing energy for tumor cells, and inducing osteoclast differentiation. (2) Quantitative magnetic resonance imaging can accurately quantify adipose tissue and measure the change of fat content in bone marrow, which is helpful for the diagnosis of bone metastasis. (3) Magnetic resonance spectroscopy can reflect different metabolites through different proton precession frequencies, so it can be used for fat quantification, and is currently used as an auxiliary test to evaluate metastatic fractures. (4) Chemical shift encoding-based water–fat imaging can separate water and fat signals in positive and inverse phases, so as to measure adipose tissue signals, with high sensitivity, specificity and accuracy in differentiating benign and malignant vertebral fractures.  Figures and Tables | References | Related Articles | Metrics

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Mammalian pluripotent stem cells: effects on creating disease models, pathogenesis, drug discovery and personalized treatment Xu Wenqiang, Chen Haolin, Yan Chang, Xu Tao, Xie Yabin, Li Xueling 2025, 29 (1):  136-146.  doi: 10.12307/2024.722 Abstract ( 14 )   PDF (1604KB) ( 9 )   Save BACKGROUND: The self-renewal and multi-directional differentiation of pluripotent stem cells possess the potential to revolutionize people’s understanding of biology, medicine, development, and disease. Stem cells play an important role in the early stage of embryonic development, and the study of them could be beneficial to understanding of the basic principles of biological development and tissue or organ formation, exploring the potential mechanisms of various diseases, studying the repair and regeneration of damaged tissues or organs, and promoting drug discovery and personalized treatment. OBJECTIVE: To review the research progress of pluripotent stem cells, summarize and categorize the fundamental types of pluripotent stem cells, and elucidate the lineage situations of various types of pluripotent stem cells in common mammals. METHODS: PubMed, Web of Science, CNKI, and WanFang databases were searched systematically, with the keywords “pluripotent stem cells; embryonic stem cells; induced pluripotent stem cells; expanded potential stem cells; livestock pluripotent stem cells” in English and Chinese. The 99 articles related to mammalian pluripotent stem cells were systematically screened according to inclusion and exclusion criteria, and then reviewed. RESULTS AND CONCLUSION: (1) According to classical theory in mouse embryonic stem cell research, the pluripotent state of stem cells is divided into two forms: naïve and primed. Naïve state corresponds to the inner cell mass of pre-implantation embryos before attachment to the uterine wall, while primed state corresponds to the epiblast after implantation. These two states exhibit significant differences in epigenetic features, transcriptional activity, external signal dependency, and metabolic phenotype. It is later discovered that there is an intermediate state between naïve and primed called formative pluripotency. Therefore, the pluripotency of pluripotent stem cells is a continuous developmental process rather than a unique cell state. (2) In addition to obtaining pluripotent stem cells from the inner cell mass, there are various methods and lineages for acquiring pluripotent stem cells, including embryonic germ cells established using primitive germ cells from mouse embryos, induced pluripotent stem cells created by the dedifferentiation of adult mouse and human fibroblasts with four factors—Oct3/4, Sox2, c-Myc, and Klf4; embryonic stem cell-like cell lines cultured from somatic cell nuclear transfer, parthenogenesis, neonatal or adult testicular or ovarian tissue, very small embryonic-like stem cells derived from various adult tissues and expanded pluripotent stem cells derived from pre-implantation stages. These pluripotent stem cells all share the common characteristics of continuous self-renewal, expressing core pluripotency factors and possessing the ability to differentiate into the three primary germ layers. (3) Currently, pluripotent stem cells are being used for disease modeling to study the mechanisms of various diseases and develop new drugs. Simultaneously, scientists are attempting to use pluripotent stem cells to cultivate various tissues and organs, offering new possibilities for regenerative medicine and transplantation. However, the clinical application of pluripotent stem cells faces safety challenges, including issues of cell mutations and immune rejection. Continual improvement in the methods of generating pluripotent stem cells will make them safer and more efficient for clinical applications. (4) Based on the methods of obtaining and lineage establishment of pluripotent stem cells in mice and humans, various types of pluripotent stem cells have been established in livestock, including embryonic stem cells, induced pluripotent stem cells, germ lineages of pluripotent stem cells, and expanded potential stem cells. Research on livestock pluripotent stem cells opens up new avenues for animal reproduction, breeding, genetic engineering, disease modeling, drug screening, and the conservation of endangered wildlife.  Figures and Tables | References | Related Articles | Metrics

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Mechanism of postoperative abdominal adhesion formation and therapeutic prospect of mesenchymal stem cell exosomes Zhang Xingzhou, Wei Ming, Dong Guoqiang, Du Wei, Luo Yiwen, Zhang Nan 2025, 29 (1):  147-155.  doi: 10.12307/2024.744 Abstract ( 18 )   PDF (1337KB) ( 5 )   Save BACKGROUND: The formation of postoperative abdominal adhesions is a complicated process, and the prevention of postoperative adhesions is an urgent problem in clinic. OBJECTIVE: To analyze the mechanism of adhesion at cellular and molecular levels, and to provide theoretical basis for the prevention and treatment of adhesion by mesenchymal stem cell exosomes. METHODS: “Abdominal adhesion, pelvic adhesion, postoperative adhesion, epithelial mesenchymal transformation, mesenchymal stem cells, stem cell exosomes, mesenchymal stem cell exosomes” were selected as Chinese and English search terms. We searched PubMed, CNKI, and Chinese biomedical literature and screened relevant articles on postoperative abdominal adhesion and mesenchymal stem cell exosomal intervention published from inception to August 2023. After systematic analysis, 54 articles were finally included for the review. RESULTS AND CONCLUSION: (1) Any pathological factors such as peritoneal inflammation, mechanical injury, tissue ischemia, and foreign body implantation cause peritoneal surface injury, resulting in postoperative abdominal adhesion. The formation process of adhesion includes the interaction of peritoneal mesothelial cell repair, inflammatory response, fibrinolytic system, coagulation pathway and other processes, involving a variety of cytokines and signaling pathways. Wnt/β-catenin pathway can induce fibrosis and angiogenesis, and cooperate with transforming growth factor-β/Smads signaling pathway to stimulate fibroblast proliferation and cause peritoneal fibrosis. Meanwhile, nuclear factor-κB signaling pathway up-regulates the expression of cellular inflammatory factors, promotes fibroblast proliferation, and plays a key role in the process of tissue fibrosis. (2) The paracrine function of stem cells is an important direction of molecular intervention in abdominal adhesions based on regenerative medicine. It can participate in a variety of complex cytokines and signaling pathways involved in abdominal adhesions. (3) Compared with traditional methods for treating abdominal adhesions, mesenchymal stem cell exosome has biological activity and is safe to use. Mesenchymal stem cell exosomes without special culture and expansion have lower immunogenicity, longer stability and other advantages, can guide a normal repair and healing through a variety of ways. (4) Mesenchymal stem cell exosome has been proven to be involved in regulating the above processes of adhesion formation in previous studies, showing potential application prospects in clinical studies. However, further clinical studies are needed to explore appropriate treatment options for mesenchymal stem cell exosomes to address the problem of clinical translation. Figures and Tables | References | Related Articles | Metrics

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Isolation technique and application of platelet-derived extracellular vesicles from platelet-rich plasma Li Jiao, Li Xiaofeng, Li Jianping 2025, 29 (1):  156-163.  doi: 10.12307/2024.724 Abstract ( 19 )   PDF (939KB) ( 5 )   Save BACKGROUND: Platelet-derived extracellular vesicles are the most abundant vesicles in the circulation, rich in bioactive molecules, genetic material, proteins and other information molecules, involved in cellular communication and material exchange, not only has good procoagulant activity, but also has the promotion of tissue repair and regeneration, and has a wide range of applications in regenerative medicine.  OBJECTIVE: To elaborate the secretion mechanism of platelet-derived extracellular vesicles, their application in regenerative medicine, and limiting factors for clinical transformation, and to provide some theoretical support for the clinical translation of platelet-derived extracellular vesicles. METHODS: A computerized search of the PubMed database from January 2005 to August 2023 was applied to articles relating to platelet-derived extracellular vesicles with the search terms “platelet-derived, platelet-rich plasma, extracellular vesicles, isolated, microvesicles exosomes, applications”. A total of 62 articles that met the subject criteria were finally included. RESULTS AND CONCLUSION: (1) Activated platelet-derived extracellular vesicles produce two types of vesicles, platelet-derived microparticles, whose secretion may be associated with the asymmetry of the actin cytoskeleton, and platelet-derived exosomes, which may be associated with the regulation of H+-ATPase. (2) Platelet-derived extracellular vesicles are potential effectors of platelet concentrates and platelets themselves, and may intervene in tissue regeneration by promoting angiogenesis, influencing cellular behavior, promoting coagulation and hemostasis, and exerting inflammatory effects. (3) Platelet-derived extracellular vesicles have been reported preclinically in the field of regenerative medicine such as tissue injury, muscle regeneration, cartilage regeneration, and osteoarthritis, and clinical trial data are available as potential therapeutic approaches for wound healing. However, factors such as isolation methods, sample sources, and the types of activators limit the clinical translation of platelet-derived extracellular vesicles into the field of regenerative medicine. (4) In the future, platelet-derived extracellular vesicles may become a cell-free alternative to platelet-rich plasma in regenerative medicine, but the clinical translation of platelet-derived extracellular vesicles needs to actively search for specific markers to differentiate platelet-derived microparticles from platelet-derived exosomes. The mechanism of activator-stimulated platelet-derived extracellular vesicle production, as well as the optimal method of platelet-derived extracellular vesicle collection, the optimal method of storage, the shelf life of the platelet-derived extracellular vesicles, the recommended dosage of platelet-derived extracellular vesicles for clinical application, and the optimal clinical indications need to be further investigated.  Figures and Tables | References | Related Articles | Metrics

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Enhancing potential of mesenchymal stem cell exosomes for osteoarthritis by adjusting cell culture condition Qian Yan, Liu Qisong 2025, 29 (1):  164-174.  doi: 10.12307/2024.745 Abstract ( 18 )   PDF (1062KB) ( 6 )   Save BACKGROUND: Exosomes derived from mesenchymal stem cells are prospective cell-free alternatives for treating osteoarthritis. Their therapeutic activity and clinical transformation potential can be further improved by adjusting cell culture condition.  OBJECTIVE: To review the effect of cell culture conditions on exosome activity and to analyze its clinical transformation potential. METHODS: Articles concerning osteoarthritis/cartilage repair and mesenchymal stem cell-derived exosomes were retrieved on CNKI and PubMed using “exosomes, mesenchymal stem cells, osteoarthritis or cartilage repair” as Chinese search terms and “exosomes or extracellular vesicles, mesenchymal stem cells, osteoarthritis or cartilage repair” as English search terms. The search time was from 2010 to 2023. Finally, 100 articles were included for summary and analysis.  RESULTS AND CONCLUSION: (1) During cell culture, providing a physical environment favorable for chondrocyte growth or adding chondroprotective small molecules, chondrogenic factors, or inflammatory factors, can further improve the regulatory activity of exosomes secreted by mesenchymal stem cells in maintaining chondrocyte phenotype, promoting cartilage regeneration, and immunosuppression. Therefore, other physical or chemical factors with similar characteristics may also improve the effects of exosomes secreted by mesenchymal stem cells for treating osteoarthritis. (2) Some treatments during cell culture, such as hypoxia induction, pulsed electromagnetic field stimulation, bioreactor, and chondroprotective molecule (e.g., human parathyroid hormone 1-34) stimulation are safe and scalable, which allows for the production of clinical-grade exosomes secreted by mesenchymal stem cells for osteoarthritis treatment. (3) Mesenchymal stem cell exosomes are expected to achieve modified treatment of osteoarthritis, and the feasibility of clinical transformation can be further improved by adjusting the cell culture regimen to enhance the therapeutic activity. Figures and Tables | References | Related Articles | Metrics

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Long non-coding RNA directly or indirectly affects osteoporosis through p38MAPK signaling pathway Qin Hao, Kang Teng, Liu Gang 2025, 29 (1):  175-184.  doi: 10.12307/2024.728 Abstract ( 24 )   PDF (1784KB) ( 5 )   Save BACKGROUND: In recent years, numerous studies have found that long non-coding RNA is involved in the occurrence and development of osteoporosis. p38MAPK signaling pathway is involved in the differentiation of bone marrow mesenchymal stem cells, osteoblasts and osteoclasts, and participates in the development of osteoporosis. LncRNA can directly or indirectly participate in the occurrence and development of osteoporosis by affecting the p38MAPK signaling pathway.  OBJECTIVE: To review the effect of long non-coding RNA directly or indirectly on the progression of osteoporosis through the p38MAPK signaling pathway, and to provide a new idea for long non-coding RNA in the prevention and treatment of osteoporosis.  METHODS: PubMed, CNKI, and Wanfang databases were searched with “long non-coding RNA, osteoporosis, mesenchymal stem cells, osteoblasts, osteoclasts, p38 signaling pathway” as the Chinese and English search terms. Old, repeated and low-credibility views were excluded. The retrieved literature was summarized, summed up, and analyzed. Seventy-six representative articles were selected. RESULTS AND CONCLUSION: (1) Long non-coding RNA participates in the prevention and treatment of osteoporosis through a variety of ways, including promoting the osteogenic differentiation of bone marrow mesenchymal stem cells, promoting the differentiation and secretion activity of osteoblasts, inhibiting the proliferation and bone resorption of osteoclasts, and regulating the activation or inhibition of osteoblast-related cellular pathways. Activation of p38MAPK signaling pathway can delay the progression of osteoporosis, and inhibition of p38MAPK signaling pathway can inhibit the absorption of osteoclasts, thereby affecting the occurrence and development of osteoporosis. (2) The overexpression or low expression of the corresponding long non-coding RNA can affect the proliferation or differentiation of osteoblasts and osteoclasts through the p38MAPK signaling pathway, regulate the process of bone remodeling, and then affect the occurrence and development of osteoporosis. A large number of basic research results show that long non-coding RNA and p38MAPK signaling pathway may be potential application and clinical translation value in the treatment of osteoporosis. Moreover, the corresponding long non-coding RNA overexpression or low expression lentivirus, transfection plasmid, and the corresponding p38MAPK signaling pathway inhibitor have been confirmed to have targeted regulatory effects in vitro cell experiments and animal models. (3) Therefore, targeting long non-coding RNA and p38MAPK signaling pathways to regulate the differentiation and function of bone marrow mesenchymal stem cells or inhibiting the proliferation and differentiation of osteoclasts may provide an innovative therapeutic strategy to delay the progression of osteoporosis. Figures and Tables | References | Related Articles | Metrics

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Regulating ferroptosis of osteoblasts by traditional Chinese medicine in treatment of steroid-induced avascular necrosis of femoral head Zhang Mianyu, Han Jie, Zeng Hao, Chen Xiangshan, Gao Zhengang 2025, 29 (1):  185-192.  doi: 10.12307/2025.002 Abstract ( 19 )   PDF (1368KB) ( 6 )   Save BACKGROUND: Some studies have found that ferroptosis of osteoblasts can be an important mechanism to induce the occurrence and development of hormone-induced femoral head necrosis. With the development of Chinese medicine, some scholars have found that some Chinese medicine monomer, Chinese medicine compound and Chinese patent medicine can regulate the ferroptosis of osteoblasts through various pathway mechanisms, and finally play a role in the treatment of steroid-induced avascular necrosis of femoral head.   OBJECTIVE: To investigate the relationship between ferroptosis and steroid-induced avascular necrosis of femoral head and the mechanism of Chinese medicine regulating ferroptosis of osteoblasts in the treatment of steroid-induced avascular necrosis of femoral head, so as to provide new ideas for the diagnosis and treatment of steroid-induced avascular necrosis of femoral head.  METHODS: With “ferroptosis, steroid-induced avascular necrosis of femoral head, osteoblast, Chinese herbal medicine, glucocorticoid, iron metabolism, reactive oxygen species, glutathione peroxidase” as Chinese search terms, and “ferroptosis, hormonal necrosis of the femoral head, osteoblast, Chinese herbal medicine, glucocorticoid, iron metabolism, ROS, GPX4” as English search terms, the search was conducted on CNKI, PubMed, WanFang, VIP and other databases. The relevant articles on osteoblast ferroptosis and steroid-induced avascular necrosis of femoral head and the regulation of Chinese herbal medicine intervention from the establishment of each database to 2023 were screened. Finally, 76 articles were systematically analyzed.  RESULTS AND CONCLUSION: (1) Ferroptosis of osteoblasts plays an important role in the pathogenesis of steroid-induced avascular necrosis of femoral head. (2) The occurrence of ferroptosis in osteoblasts is regulated by a variety of mechanisms, such as intracellular iron overload causing ferroptosis. Lipid peroxidation damages cell membrane and causes ferroptosis. Cystine/glutamate reverse transporter induced ferroptosis by influencing glutathione level and glutathione peroxidase 4 activity. Fenton reaction in the cell produces a large number of reactive oxygen species and causes ferroptosis. (3) Chinese medicine monomer icariin, Chinese medicine compound Qinge pills and Chinese patent medicine Bushen Huoxue granules can regulate the occurrence of osteoblast ferroptosis, and help to prevent and treat steroid-induced avascular necrosis of femoral head. (4) The mechanism of ferroptosis in osteoblasts is still unclear. Further investigation on the mechanism of action of both is expected to provide a new choice for clinical treatment of steroid-induced avascular necrosis of femoral head.   Figures and Tables | References | Related Articles | Metrics

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Application of single-cell RNA sequencing technology in Parkinson’s disease Liu Ziyu, Geng Dandan, Zhang Runjiao, Liu Qing, Li Yibo, Wang Hongfang, Xie Wenmeng, Wang Wenyu, Hao Jiaxin, Wang Lei 2025, 29 (1):  193-201.  doi: 10.12307/2025.003 Abstract ( 16 )   PDF (1534KB) ( 3 )   Save BACKGROUND: Parkinson’s disease has the main pathological changes in the midbrain, especially in the dense substantia nigra, leading to impaired motor and non-motor function in patients. At present, research is limited by cellular heterogeneity, and its pathogenesis still needs to be further elucidated. In recent years, single-cell RNA sequencing (scRNA-seq) has gradually been applied in neurodegenerative diseases, which is of great significance for understanding intercellular heterogeneity, disease development mechanisms, and treatment strategies. OBJECTIVE: To review the research progress of scRNA-seq technology applied to Parkinson’s disease in recent years, providing a theoretical basis for the application of scRNA-seq in the treatment and diagnosis of Parkinson’s disease.  METHODS: The first author used a computer system to search for relevant literature in the CNKI, WanFang, PubMed, and Web of Science databases, with the Chinese search terms “single-cell RNA sequencing, Parkinson’s disease, cell heterogeneity, cell subtypes, dopaminergic neurons, glial cells” and English search terms “single-cell RNA seq, Parkinson disease, heterogenicity, subtypes, dopaminergic neurons, glial cells.” 71 articles were ultimately included for review and analysis. RESULTS AND CONCLUSION: (1) scRNA-seq is a high-throughput experimental technique that utilizes RNA sequencing at the single-cell level to quantify gene expression profiles in specific cell populations, revealing cellular mysteries at the molecular level. Compared with traditional sequencing techniques, scRNA-seq technology is used to reveal the diversity of cell types and changes in specific gene expression in complex tissues under various physiological and pathological conditions through automatic clustering analysis of cell transcriptome. (2) By using scRNA-seq, the development process of dopaminergic neurons and the unique functional characteristics of various cell subtypes are elucidated, in order to better understand potential therapeutic molecular targets. (3) The use of scRNA-seq analysis has improved our understanding of the response of Parkinson’s disease glial cells, enabling us to comprehensively map and characterize different cell type populations, identify specific glial cell subpopulations related to neurodegeneration, and draw valuable single cell maps as reference data for future research. (4) The application of scRNA-seq to detect embryonic mice and stem cells will help improve the in vitro differentiation protocol and quality control of cell therapy, as well as evaluate the overall cell quality and developmental stage of dopaminergic neurons derived from stem cells.  Figures and Tables | References | Related Articles | Metrics

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Application and regulatory challenges of organoid technology in medical field Cheng Weilu, Wang Zehua, Zhang Yidan, Liu Yinghui 2025, 29 (1):  202-210.  doi: 10.12307/2025.001 Abstract ( 27 )   PDF (941KB) ( 4 )   Save BACKGROUND: 3D organoids have characteristics that resemble physiological tissues and to some extent mimic organ function, making them excellent models for applications ranging from basic development/stem cell research to personalized medicine. OBJECTIVE: To review and discuss the types of diseases and application areas such as tumor modeling that organoids can be applied to, as well as their regulatory status and challenges. METHODS: With “organoid, stem cell, disease model, 3D printing technology, medical field” as Chinese and English search terms, we searched PubMed, Elsevier, WanFang, and CNKI databases to summarize and analyze organoid products at home and abroad, summarize the application of organoid technology in the medical field, and prospect the future development of organoid products in the medical field. RESULTS AND CONCLUSION: Organoids can break the limitations of traditional cell and animal models, avoid the ethical problems existing in clinical research, and have a high similarity to the source organ, a more similar performance to the physiology and pathology of human systems, and genetic stability, which has great advantages in current research. Organoids have been applied in the following fields: efficacy evaluation studies (preclinical models), including intestinal organoids, kidney organoids, liver organoids, gallbladder organoids, lung organoids, brain organoids, heart organoids, skin organoids, and reproductive system organoids; research on infectious diseases; cancer research and precision therapy; regenerative medicine; immune organoids. Although the United States, the European Union and China do not have perfect regulatory provisions, they are trying to promote the formulation of organoid regulatory laws and regulations. In China, although no organoid medical device products have been listed for the time being, its related regenerative medicine products have made breakthroughs. Figures and Tables | References | Related Articles | Metrics

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Instructions for Authors- Chinese Journal of Tissue Engineering Research (CJTER) 2025, 29 (1):  211-220.  doi: 10.12307/2025.050 Abstract ( 28 )   PDF (746KB) ( 3 )   Save Related Articles | Metrics