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08 January 2026, Volume 30 Issue 1 Previous Issue    Next Issue

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Protection of exosomes derived from bone marrow mesenchymal stem cells of different mouse ages on radiation-induced lung injury Zhang Tingting, Li Yalong, Yue Haodi, Li Yanjun, Geng Xiwen, Zhang Yuwei, Liu Xiaozhuan 2026, 30 (1):  1-9.  doi: 10.12307/2025.575 Abstract ( 50 )   PDF (2470KB) ( 82 )   Save BACKGROUND: Mesenchymal stem cells show extremely therapeutic potential for radiation-induced lung injury through delivering exosomes. Age is a primary factor affecting the function and biological efficacy of mesenchymal stem cells. OBJECTIVE: To investigate the protective effects of exosomes derived from bone marrow mesenchymal stem cells of different mouse ages on radiation-induced lung injury in mice.   METHODS: Bone marrow mesenchymal stem cells of young mice and old mice were obtained by whole bone marrow adherent culture. The exosomes were isolated from the supernatant of passage 3 bone marrow mesenchymal stem cells. Ten 2-month-old C57BL/6J mice were randomly selected as the control group after anesthesia and not irradiated. The remaining 30 2-month-old C57BL/6J mice were used to establish a mouse radiation-induced lung injury model and were randomly divided into three groups. Exosomes derived from bone marrow mesenchymal stem cells of young mice, exosomes derived from bone marrow mesenchymal stem cells of old mice, and PBS were injected through the tail vein, respectively. The survival rate of mice was monitored. The lung function, lung inflammation and fibrosis were assessed at 1 and 12 weeks after irradiation. RESULTS AND CONCLUSION: (1) The concentrations of particles and proteins in exosomes derived from bone marrow mesenchymal stem cells of young mice were higher than those in exosomes derived from bone marrow mesenchymal stem cells of old mice. (2) Compared with the control group, the survival rate of mice in the PBS group was low, and lung inflammation was obvious at week 1 after irradiation, and the levels and mRNA expressions of interleukin-1β, interleukin-6, and tumor necrosis factor-α were increased. Collagen deposition in lung tissues was observed at week 12 after irradiation, and the mRNA level of E-cadherin was decreased, while the mRNA levels of α-smooth muscle actin, transforming growth factor-β1, and β-catenin were increased. (3) Compared with the PBS group, the survival rate of mice in the exosome group was significantly improved, and the level of proinflammatory factors and their mRNA expression were reduced at week 1 after irradiation, the mRNA level of E-cadherin was increased, and the mRNA levels of α-smooth muscle actin, transforming growth factor β1 and β-catenin were reduced at week 12 after irradiation. (4) Among all the above indicators, the therapeutic effect of exosomes derived from bone marrow mesenchymal stem cells of young mice was better than that of exosomes derived from bone marrow mesenchymal stem cells of old mice. (5) The results showed that exosomes derived from bone marrow mesenchymal stem cells of young mice contained more particles and proteins, and the effect of alleviating early inflammation and late fibrosis of radiation-induced lung injury in mice was better than that of exosomes derived from bone marrow mesenchymal stem cells of old mice. Figures and Tables | References | Related Articles | Metrics

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Senescence of human bone marrow mesenchymal stromal cells with increasing age is not dependent on the mediation of endogenous retroviruses Wang Yaping, Gao Tianyun, Wang Bin 2026, 30 (1):  10-20.  doi: 10.12307/2026.539 Abstract ( 68 )   PDF (3018KB) ( 375 )   Save BACKGROUND: Aging of human body may be due to the senescence and depletion of various stem cells in the body. Bone marrow mesenchymal stromal cells have important physiological functions and have shown certain therapeutic effects on various diseases. It is of great significance to study the senescence and mechanism of bone marrow mesenchymal stromal cells.  OBJECTIVE: To investigate whether human bone marrow mesenchymal stromal cells exhibit senescence phenotypes with increasing donor age, and further determine whether endogenous retrovirus drives the senescence of bone marrow mesenchymal stromal cells, offering a novel reference for the investigation of stem cell senescence mechanism. METHODS: The senescence of bone marrow mesenchymal stromal cells at different ages was characterized by flow cytometry, β-galactosidase staining, qPCR, western blotting, and EdU fluorescence imaging. Bone marrow mesenchymal stromal cells and cell culture supernatant were collected from donors of different ages. The content of human endogenous retrovirus was detected by qPCR. Furthermore, highly sensitive droplet digital PCR was used to detect the expression of endogenous retrovirus-like particles in the cell culture supernatant. The content of endogenous retrovirus in bone marrow plasma samples of different ages was detected by ELISA. RESULTS AND CONCLUSION: Bone marrow mesenchymal stromal cells exhibited obvious senescence with increasing age, including significant morphological changes, increased proportion of β-galactosidase positive cells, increased expression of senescence markers P16 and P21 protein, decreased expression of LMNB1 protein, and reduced cell proliferation ability. There was no significant difference in the content of endogenous retrovirus in bone marrow mesenchymal stromal cells at different ages, almost no endogenous retrovirus-like particles in the cell culture supernatant. There was no significant difference in endogenous retrovirus-like particles detected in bone marrow plasma samples at different ages. These findings indicate that human bone marrow mesenchymal stromal cells have normal physiological senescence with increasing age, but the mechanism of senescence is not mediated by abnormal activation of endogenous retroviruses, which may have a more complex driving mechanism.  Figures and Tables | References | Related Articles | Metrics

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Engineered stem cell bionic periosteum coordinates immune inflammation and vascularization to promote bone regeneration Sun Huiwen, Guo Qiangqiang, Wang Wei, Wu Jie, Xi Kun, Gu Yong 2026, 30 (1):  21-33.  doi: 10.12307/2025.551 Abstract ( 51 )   PDF (3394KB) ( 111 )   Save BACKGROUND: Autologous bone, allogeneic bone or artificial bone has been used to promote bone defect repair in the clinic, but the rate of non-healing is still high. The key is to ignore the importance of periosteum in the bone healing process. In the early stage of the project, the project team constructed an electrospinning membrane loaded with vascular endothelial growth factor to highly simulate the intramembranous osteogenesis of natural periosteum at the bone defect site, which promoted bone regeneration to a certain extent. However, the injured area often faces the dilemma of severe inflammatory response mediated by macrophages and lack of seed cells, resulting in the risk of inactivation or diffusion of delivered biological factors. Therefore, it is necessary to further optimize and coordinate the immune regulation and angiogenesis functions of biomimetic periosteum to promote bone repair.  OBJECTIVE: To investigate the physicochemical properties of stem cell-engineered bionic periosteum and its role in regulating the inflammatory microenvironment to promote bone repair.  METHODS: By combining L-polylactic acid-based microsol electrospinning, type I collagen self-assembly and gel stem cell transplantation technology, a bionic periosteum (M@C-B) was constructed, in which the core layer loaded with vascular endothelial growth factor and the shell layer delivered bone marrow mesenchymal stem cells to regulate the immune microenvironment of bone defects. The physicochemical properties of the periosteum were characterized by scanning electron microscopy, transmission electron microscopy, and Fourier transform infrared spectroscopy. A co-culture system was established between the bionic periosteum and macrophages, bone marrow mesenchymal stem cells and human umbilical vein endothelial cells to explore immune regulation and in vitro osteogenic and angiogenic abilities. Finally, the osteogenic properties of the stem cell engineered bionic periosteum were further verified in a rat femoral condyle defect model. RESULTS AND CONCLUSION: (1) Transmission electron microscopy results showed that the micro-sol electrospinning (MS) formed a distinct core-shell structure. Scanning electron microscopy indicated that after the assembly of the collagen-I artificial periosteum (M@C) on the surface of the vascular endothelial growth factor-loaded micro-sol, a distinct “spider web-like” fibrous structure was deposited. Infrared spectroscopy further confirmed the successful self-assembly of collagen-I. Release experiments demonstrated that the M@C group mitigated the burst release phenomenon compared to the MS group, maintaining internal vascular endothelial growth factor activity and sustained release. (2) Live/dead cell staining and CCK-8 assay showed that bone marrow mesenchymal stem cells proliferated well and survived on three types of artificial periosteum: MS, purely aligned poly(L-lactic acid) (PLLA) surface self-assembled collagen-I artificial periosteum (PLLA@C), and vascular endothelial growth factor-loaded micro-sol fiber surface self-assembled collagen-I-bone marrow mesenchymal stem cells artificial periosteum (M@C-B). Among them, the M@C-B group had the highest number of live cells and the fastest proliferation rate. (3) Alkaline phosphatase staining, alizarin red staining, and osteopontin immunofluorescence staining showed that the PLLA@C and M@C-B groups significantly promoted osteogenic differentiation of bone marrow mesenchymal stem cells. Angiogenesis experiments demonstrated that the vascular endothelial growth factor-loaded groups (MS and M@C-B) had longer blood vessel lengths and more reticular vascular-like structures with more cross-linked nodes, with the M@C-B group being the most prominent. (4) Immunofluorescence and flow cytometry showed that artificial periosteum in the M@C-B group significantly inhibited the pro-inflammatory macrophage phenotype and promoted the polarization of macrophages towards the anti-inflammatory M2 phenotype. (5) In vivo studies further confirmed that the M@C-B group showed superior bone mineral density, trabecular thickness, relative bone volume, and trabecular spacing compared to other groups. (6) These results indicate that bone marrow mesenchymal stem cell-engineered artificial periosteum, through the rapid regulation of the bone defect immune microenvironment by the collagen-I-bone marrow mesenchymal stem cells outer phase and the sustained release of vascular endothelial growth factor by the micro-sol electrospinning core-shell structure of the inner phase, synergistically promotes bone healing. Figures and Tables | References | Related Articles | Metrics

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Bone marrow mesenchymal stem cell nanovesicles fusion neutrophil apoptotic bodies promote skin wound healing in diabetic mice Sun Zhanpeng, Liu Sen, Shi Ling, Chen Kaiyuan, Song Meichen, Wu Yan, Yu Jing 2026, 30 (1):  34-42.  doi: 10.12307/2026.507 Abstract ( 48 )   PDF (1798KB) ( 90 )   Save BACKGROUND: Nanocell vesicles possess functions such as re-epithelialization, antioxidation, anti-inflammation, and regulation of extracellular matrix remodeling. Meanwhile, apoptotic bodies have the immunomodulatory effects. Therefore, the combination of the two to form nanofusion vesicles can synergistically promote the healing of diabetic skin wounds.  OBJECTIVE: To elucidate the impact of nanofusion vesicles on skin wound healing in a diabetic murine model. METHODS: (1) Material preparation and characterization: The primary bone marrow mesenchymal stem cells of C57BL/6J neonatal mice and the neutrophil apoptotic bodies of C57BL/6J mice were isolated and extracted. The nanofusion vesicles were prepared by micro-extrusion mechanism. (2) In vitro experiment: MTT assay was used to detect the proliferative effect of different concentrations of nanofusion vesicles on NIH-3T3 cells and human umbilical vein endothelial cells. Reactive oxygen species fluorescence probe was used to detect the antioxidant effect of nano-fusion vesicles on NIH-3T3 cells treated with hydrogen peroxide (H2O2). The inhibitory effect of nanofusion vesicles on RAW 264.7 macrophage inflammation induced by lipopolyside was detected by real-time quantitative RT-qPCR. (3) In vivo experiment: 36 male C57BL/6J mice were employed to develop a murine model of diabetes mellitus. Following the successful induction of diabetes, two circular full-thickness wounds, each with a diameter of 6 mm, were created on either side of the diabetic mice’s spine using a skin punch. The mice were divided into three groups by random number table method. The control group was injected with 0.1 mL of phosphate buffer solution. The nanovesicle group was injected with 0.1 mL nanovesicles (25 μg/mL). The nanofusion vesicle group was injected with 0.1 mL nanofusion (25 μg/mL) vesicles. After treatment for three consecutive days, the wound healing and histomorphological changes were observed. RESULTS AND CONCLUSION: (1) In vitro experiment: nanofusion vesicles, when administered at concentrations ranging from 0 to 100 μg/mL, exhibited no toxic effects and promoted the proliferation of NIH-3T3 and HUVEC cell lines. Notably, a concentration of 25 μg/mL nanofusion vesicle significantly enhanced the proliferation of NIH-3T3 cells. Furthermore, the survival rate of human umbilical vein endothelial cells was observed to increase in correlation with escalating concentrations of nanofusion vesicles. Nanofusion vesicles had a good antioxidant effect. In comparison to the H2O2 group, the fluorescence signal indicative of reactive oxygen species was progressively diminished in both the nanovesicle group and the nanofusion vesicle group. Furthermore, nanofusion vesicles possessed anti-inflammatory capabilities, effectively mitigating the inflammatory response in macrophages triggered by lipopolysaccharide stimulation. (2) In vivo experiment: Hematoxylin-eosin and Masson's trichrome staining revealed that in comparison to the control group, both the nanovesicle group and the nanofusion vesicle group exhibited a significant increase in granulation tissue formation and collagen fiber deposition within the wounds by day 6. Notably, the nanofusion vesicle group displayed the most pronounced effects. On day 12, the wound of nanofusion vesicle group was significantly reduced, and the healing rate was significantly faster than that of other groups (P < 0.01), and the effect of promoting wound healing was the most significant. Our findings demonstrated that nanofusion vesicles exhibited superior pro-cell proliferative, antioxidant, and anti-inflammatory properties, thereby exerting a beneficial effect on the promotion of skin wound healing in diabetic mouse models. Figures and Tables | References | Related Articles | Metrics

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Effect of miR-196b-5p in adipose-derived stem cell exosomes on burn wound healing in rats Zuo Na, Tang Qi, Yu Meng, Tao Kai 2026, 30 (1):  43-49.  doi: 10.12307/2025.927 Abstract ( 40 )   PDF (2719KB) ( 108 )   Save BACKGROUND: Currently, miR-196b-5p has been found to play a role in cell proliferation, migration and inhibition of scar hyperplasia, but there is a lack of relevant studies on whether it plays a role in the process of wound healing. OBJECTIVE: To investigate the effect of miR-196b-5p in adipose stem cell-derived exosomes on burn wound healing.  METHODS: The models of deep second degree skin burn in SD rats were established and randomly divided into four groups: blank control group, exosome group, agomiR-196b-5p group, and exosome + antagomiR-196b-5p group, with 10 rats in each group. PBS, adipose-derived stem cell-derived exosomes, miR-196b-5p agonist, and miR-196b-5p inhibitor were injected around the wound according to different groups. Wound healing was observed immediately after injury and on days 7, 14, and 21 after injury. On day 7 after surgery, hematoxylin-eosin staining was used to observe the expression of inflammation in the wound surface. On day 14 after suregery, Masson staining was used to observe the expression of collagen and immunohistochemical staining was used to observe the expression of CD31 in the wound surface. On day 7 after surgery, western blot assay was performed to detect the expression of α-smooth muscle actin and type I collagen in the wound surface.  RESULTS AND CONCLUSION: (1) The wound healing was faster in the agomiR-196b-5p group, while it was slower in the blank control group and the exosome+antagomiR-196b-5p group. (2) Compared with the blank control group and the exosome+antagomiR-196b-5p group, the wound infiltration of inflammatory cells was less in the exosome group and the agomiR-196b-5p group, and the expression of CD31 was significantly increased (P < 0.01). (3) Compared with the blank control group and the exosome+antagomiR-196b-5p group, the expression levels of α-smooth muscle actin and type I collagen were increased in the exosome group and the agomiR-196b-5p group (P < 0.05). These findings indicate that miR-196b-5p in adipose stem cell-derived exosomes can promote burn wound healing in rats. Figures and Tables | References | Related Articles | Metrics

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Effect of dimethylglyoxal glycine on osteogenic, adipogenesis differentiation, and mitophagy of human bone marrow mesenchymal stem cells Chen Qiheng, Weng Tujun, Peng Jiang 2026, 30 (1):  50-57.  doi: 10.12307/2025.578 Abstract ( 37 )   PDF (2384KB) ( 38 )   Save BACKGROUND: Bone marrow mesenchymal stem cells play a crucial role in treatment of diseases, such as femoral head necrosis, and the therapeutic efficacy is closely related to the quality of the cells. The empowerment of cells has become a research focus. OBJECTIVE: To investigate the effects of hypoxia mimetic dimethylglyoxal glycine pretreatment on mitophagy and differentiation capacity of human bone marrow mesenchymal stem cells. METHODS: Bone marrow mesenchymal stem cells were extracted from the bone marrow of patients’ iliac crest and cultured in vitro to the third passage. The cells were treated with dimethylglyoxal glycine at 0, 10, 50, and 100 μmol/L for 24 hours, followed by the replacement with an osteogenic induction differentiation medium, which constituted the pretreatment group. The continuous treatment group was cultured directly in osteogenic induction medium containing 0, 10, 50, and 100 μmol/L dimethylglyoxal glycine after cell adhesion. After 7 days of induction, alkaline phosphatase staining was performed to select the most favorable conditions for osteogenic differentiation for subsequent experiments, with normally cultured bone marrow mesenchymal stem cells serving as the control group. Alkaline phosphatase staining, alkaline phosphatase activity, oil red O staining, and related RT-qPCR were used to evaluate the osteogenic and adipogenic differentiation differences of bone marrow mesenchymal stem cells between the two groups. MitoSox staining was used to detect mitochondrial reactive oxygen species levels. Mito-tracker and Lyso-tracker staining were used to detect the co-localization of mitochondria and lysosomes. The fluorescent probe JC-1 was used to measure mitochondrial membrane potential. RESULTS AND CONCLUSION: Alkaline phosphatase staining indicated that the most beneficial treatment for bone marrow mesenchymal stem cell osteogenesis was pretreatment with 10 μmol/L dimethylglyoxal glycine for 24 hours. Compared with the control group, the experimental group showed enhanced alkaline phosphatase staining expression, increased alkaline phosphatase activity and osteogenic gene expression, reduced lipid droplet formation and adipogenic gene expression as indicated by oil red O staining, decreased mitochondrial reactive oxygen species production, increased co-localization of mitochondria and lysosomes, and elevated mitochondrial membrane potential. The results suggest that 10 μmol/L dimethylglyoxal glycine pretreatment can promote osteogenic differentiation of bone marrow mesenchymal stem cells, inhibit adipogenic differentiation, and enhance mitophagy.   Figures and Tables | References | Related Articles | Metrics

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Therapeutic effects of adipose-derived mesenchymal stem cells and their exosomes on dexamethasone-induced sarcopenia in mice Yuan Weiyuan, Lei Qinhui, Li Xiuqi, Lu Tiezhu, Fu Ziwen, Liang Zhili, Ji Shaoyang, Li Yijia, Ren Yu 2026, 30 (1):  58-67.  doi: 10.12307/2025.576 Abstract ( 43 )   PDF (2686KB) ( 104 )   Save BACKGROUND: Sarcopenia is an age-related condition characterized by the loss of skeletal muscle mass, strength, and/or physical function. Currently, effective treatments for sarcopenia remain limited. A new therapeutic approach to improve symptoms and prognosis of sarcopenia patients clinically was important.  OBJECTIVE: To explore the effects of canine adipose-derived mesenchymal stem cells and their exosomes on a dexamethasone-induced sarcopenia in mice. METHODS: Mesenchymal stem cells were isolated and cultured from canine adipose tissue, and identified and functionally evaluated through flow cytometry and differentiation assays for osteogenesis, adipogenesis, and chondrogenesis. Subsequently, exosomes from adipose-derived mesenchymal stem cells were extracted and characterized using transmission electron microscopy, western blot assay, and nanocoulter tracking analysis. In vitro, the effects of canine adipose-derived mesenchymal stem cells and their exosomes on myotube growth and the expression of muscle atrophy-related genes were investigated using dexamethasone-induced C2C12 myotube atrophy and aging C2C12 models. In vivo, a dexamethasone-induced mouse sarcopenia model was established and received intraperitoneal or intravenous injection of canine adipose-derived mesenchymal stem cells. Therapeutic efficacy was assessed through mouse rotarod performance, histopathological analysis, and muscle atrophy-related genes testing. RESULTS AND CONCLUSION: (1) The isolated canine adipose-derived mesenchymal stem cells highly expressed CD73, CD90, and CD105, and lowly expressed MHC-II, CD14, CD19, CD34, and CD45, and successfully differentiated into osteoblasts, adipocytes, and chondrocytes in vitro. (2) The adipose-derived mesenchymal stem cells-derived exosomes met the identification criteria in terms of particle size, electron microscopy morphology, and positive expression of specific markers. (3) Compared to the dexamethasone-induced C2C12 atrophy group, treatment with adipose-derived mesenchymal stem cells and their exosomes promoted the recovery and growth of myotubes, inhibited the expression of muscle atrophy-related genes MuRF1 and Atrogin-1. (4) Compared to the aging C2C12 group, adipose-derived mesenchymal stem cells and their exosomes significantly enhanced the recovery and growth of aged muscle tubes in aging cells. (5) Compared to the control group, the rotarod time in dexamethasone-induced sarcopenia model mice was significantly decreased (P < 0.01). After 7 days (P < 0.01, P < 0.01) and 10 days (P < 0.01, P < 0.05) of adipose-derived mesenchymal stem cells treatment via intraperitoneal and intravenous injection, rotarod time was significantly increased, respectively. After 14 days, all treatment groups showed longer rotarod times than the model group, although with no significant differences between them. (6) Compared to the control group, the cross-sectional area of anterior tibial muscle in the model group was significantly reduced (P < 0.01), and it was significantly increased after intraperitoneal and intravenous administration of adipose-derived mesenchymal stem cells (P < 0.05, P < 0.01). (7) Compared to the model group, intraperitoneal and intravenous administration of adipose-derived mesenchymal stem cells significantly inhibited the mRNA expression of MuRF1 and Atrogin-1 genes (P < 0.01, P < 0.01, P < 0.01, P < 0.01). The results indicated that adipose-derived mesenchymal stem cells and their exosomes promoted recovery and growth of atrophic myotube cells by inhibiting the expression of muscle atrophy-related genes, and both intraperitoneal and intravenous administration of adipose-derived mesenchymal stem cells provided good therapeutic effects on sarcopenia in mice. Figures and Tables | References | Related Articles | Metrics

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Scaffold-free three-dimensional human umbilical cord mesenchymal stem cell secretome repairs mouse skin injury Ma Wenjing, Zhang Jinyu, Jiang Mingxia, Xiu Bingshui, Bai Rui, Liu Yuhan, Chen Xuyi, Yuan Zengqiang, Liu Zhiqiang 2026, 30 (1):  68-77.  doi: 10.12307/2025.982 Abstract ( 31 )   PDF (3207KB) ( 73 )   Save BACKGROUND: The mesenchymal stem cell secretome contains bioactive substances, cytokines, and growth factors. Three-dimensional cell culture can regulate the secretion of these components, potentially enhancing the ability to promote injury repair. OBJECTIVE: To investigate the repair effect of three-dimensional cultured human umbilical cord mesenchymal stem cell secretome on skin injuries in mice. METHODS: Human umbilical cord mesenchymal stem cells were cultured in conventional two-dimensional culture dishes and 96-well U-bottom cell culture plates, from which their secretory components were subsequently collected. The expression of skin damage repair related secretory factors in umbilical cord mesenchymal stem cells was analyzed using RT-qPCR. The protein expression level of skin damage repair related factors in umbilical cord mesenchymal stem cell secretome was detected using enzyme-linked immunosorbent assay. The potential of human umbilical cord mesenchymal stem cell secretome to repair vascular injuries was evaluated using an immortalized human umbilical vein endothelial cell migration model. A mouse skin injury model was established, and the human umbilical cord mesenchymal stem cell secretome was injected subcutaneously. Repair effects on skin injury were assessed through wound healing rates and histopathological analysis. RESULTS AND CONCLUSION: (1) After three days of cultivation, human umbilical cord mesenchymal stem cells cultured in two dimensions exhibited a fibroblast-like, swirling growth pattern, whereas three-dimensional culture led to the formation of uniform microspheres. (2) Compared with two-dimensional culture, three-dimensional culture significantly increased the mRNA expression of transforming growth factor β and basic fibroblast growth factor in human umbilical cord mesenchymal stem cells. (3) Compared with two-dimensional culture, three-dimensional cultured human umbilical cord mesenchymal stem cell secretome significantly enhanced the protein expression of vascular endothelial growth factor, interleukin-10, and granulocyte-macrophage colony-stimulating factor in the human umbilical cord mesenchymal stem cell secretome. (4) Compared with two-dimensional culture, three-dimensional cultured human umbilical cord mesenchymal stem cell secretome significantly promoted the migration of immortalized human umbilical cord mesenchymal stem cells. (5) Compared with the untreated control group and the two-dimensional cultured human umbilical cord mesenchymal stem cell secretome, the three-dimensional cultured human umbilical cord mesenchymal stem cell secretome can significantly accelerate the skin wound healing rate and wound skin structure remodeling in mice. These results indicate that three-dimensional culture can enhance the expression of paracrine factors of human umbilical cord mesenchymal stem cells, and their secretome can significantly promote the repair of mouse skin damage. Figures and Tables | References | Related Articles | Metrics

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Effects of human umbilical cord blood platelet-rich plasma, mononuclear cells, and mesenchymal stem cells in repairing thin endometrium in rats  Mu Yanli, Hu Anchun, Xu Wenchi, Chen Panpan, Chen hao, Zhao Shuyun, Huang Guanyou, Chen Xiaojuan 2026, 30 (1):  78-92.  doi: 10.12307/2026.510 Abstract ( 44 )   PDF (2883KB) ( 78 )   Save BACKGROUND: Research has found that human umbilical cord blood platelet rich plasma and human umbilical cord blood derived mesenchymal stem cells have certain therapeutic effects on thin endometrium. However, there are currently no reports on the study of human umbilical cord blood mononuclear cells on thin endometrium, and there is a lack of relevant research comparing the three. OBJECTIVE: To explore the effects and mechanisms of human umbilical cord blood platelet rich plasma, monocytes, and mesenchymal stem cells in repairing thin endometrium in rats. METHODS: Sixty female SPF grade SD rats were randomly divided into sham operation group, model group, human umbilical cord blood platelet rich plasma group, human umbilical cord blood mononuclear cell group, and human umbilical cord blood derived mesenchymal stem cell group, with 12 rats in each group. The sham operation group received 0.5 mL physiological saline injection into the uterine horn, followed by 0.5 mL of PBS infusion after 5 minutes; The model group, human umbilical cord blood platelet rich plasma group, human umbilical cord blood mononuclear cell group, and human umbilical cord blood derived mesenchymal stem cell group were injected with 0.5 mL of 95% ethanol by volume. After 5 minutes, the remaining ethanol was aspirated and washed twice with physiological saline. Then, 0.5 mL of PBS, human umbilical cord blood platelet rich plasma, human umbilical cord blood mononuclear cells (1×107 cells/mL), and human umbilical cord blood derived mesenchymal stem cells (1×107 cells/mL) were perfused separately. During the third normal estrus cycle after reperfusion, organs, tissues and serum were collected for testing of relevant indicators. RESULTS AND CONCLUSION: (1) The macroscopic view of uterine tissue, hematoxylin eosin staining and Masson staining results: the sham operation group had intact structure, moderate endometrial thickness, and clear vascular structure. Compared with the sham operation group, the model group showed uterine atrophy, incomplete structure, significantly reduced endometrial thickness and glandular quantity, disordered vascular structure, and increased fibrosis. Compared with the model group, after treatment with human umbilical cord blood derivatives, the size, structure, and endometrial thickness of the uterus were restored (all P < 0.01), and fibrosis was reduced, with the most significant recovery observed in the human umbilical cord blood mononuclear cell group. The increase in glandular quantity was most significant in the human umbilical cord blood platelet rich plasma group (P < 0.000 1). (2) The immunohistochemistry and immunofluorescence results of uterine tissue showed that compared with the sham operation group, the expression levels of cell proliferation related indicators such as keratin 9 and vimentin, endometrial receptivity related indicators such as leukemia inhibitory factor and integrin αγβ3, platelet endothelial cell adhesion molecule, basic fibroblast growth factor, and vascular endothelial growth factor were all reduced in the model group (all P < 0.05). Compared with the model group, the above indicators were significantly increased after treatment with human umbilical cord blood derivatives. Comparison of human umbilical cord blood derivatives among groups showed that keratin 9 and vascular endothelial growth factor protein: human umbilical cord blood mononuclear cell group > human umbilical cord blood derived mesenchymal stem cell group > human umbilical cord blood platelet rich plasma group; Wave shaped protein and leukemia inhibitory factor protein: human umbilical cord blood derived mesenchymal stem cell group > human umbilical cord blood mononuclear cell group > human umbilical cord blood platelet rich plasma group; Integrin αγβ3 protein: human umbilical cord blood platelet rich plasma group > human umbilical cord blood derived mesenchymal stem cell group > human umbilical cord blood mononuclear cell group; Platelet endothelial cell adhesion molecule protein: human umbilical cord blood platelet rich plasma group > human umbilical cord blood mononuclear cell group > human umbilical cord blood derived mesenchymal stem cell group; Basic fibroblast growth factor protein: human umbilical cord blood mononuclear cell group > human umbilical cord blood platelet rich plasma group > human umbilical cord blood derived mesenchymal stem cell group. (3) Western blot analysis showed that compared with the sham operation group, the protein levels of interleukin-6, interleukin-1β, and tumor necrosis factor alpha in the model group were significantly increased (all P < 0.001), and their expression levels decreased after treatment (all P < 0.05). (4) ELISA assay showed that compared with the sham operation group, the model group had lower levels of anti Mullerian hormone, estradiol, and progesterone, and increased levels of follicle stimulating hormone and luteinizing hormone (except for luteinizing hormone, all P < 0.05). After treatment, there was a certain degree of recovery in the levels of sex hormones and anti Mullerian hormones. (5) Fertility experiments showed that compared with the sham operation group, the model group had an increase in conception time and a significant decrease in litter size (all P < 0.05). After treatment with human umbilical cord blood derivatives, the litter size of all three groups increased (P < 0.05), and no significant differences were found between the groups. This study preliminarily reveals that human umbilical cord blood mononuclear cells have a certain therapeutic effect on thin endometrium, and human umbilical cord blood platelet rich plasma, human umbilical cord blood mononuclear cells, and human umbilical cord blood derived mesenchymal stem cells have different advantages and differences in improving endometrial regeneration function, endometrial receptivity, angiogenesis, inflammation regulation, and improving pregnancy outcomes in thin endometrium. Figures and Tables | References | Related Articles | Metrics

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Effect of cannabinoid type I receptors on neuronal differentiation of human apical papilla stem cells Liu Ziwei, Nijati·Tursun, Yin Rui, Li Shuhui, Zhou Jing 2026, 30 (1):  93-100.  doi: 10.12307/2026.509 Abstract ( 26 )   PDF (1998KB) ( 9 )   Save BACKGROUND: Previous studies have demonstrated that the cannabinoid type I receptor can enhance the proliferation and neural differentiation of neural stem cells and mesenchymal stem cells. Moreover, cannabinoid type I also governs the proliferation and mineralization capacity of human apical papilla stem cells. However, there are relatively few investigations concerning the impact of cannabinoid type I overexpression on the neural differentiation of human apical papilla stem cells.   OBJECTIVE: To investigate the effect of cannabinoid type I on neural differentiation of human apical papilla stem cells in vitro.  METHODS: Healthy third molars with immature root tips that need to be removed for orthodontic treatment were collected, and human apical papilla stem cells were isolated and cultured by tissue block method combined with enzyme digestion method. Cannabinoid type I gene was introduced into human apical papilla stem cells by lentivirus-mediated transfection technique. A blank control group, a negative control group, and cannabinoid type I overexpression group were set up. The transfection effect of overexpression of cannabinoid type I lentivirus on human apical papilla stem cells was verified by Western Blot. The control group, negative control group, cannabinoid type I overexpression group and cannabinoid type I overexpression + AM251 (cannabinoid type I receptor antagonist) group were set up. Cell proliferation was detected by CCK-8 assay at 1, 5, and 10 days after neural induction. On day 10 of neural induction, the expression levels of TH, NeuroD-1, and NCAM1 genes were detected by qRT-PCR, and the protein expression levels of Nestin and TUBB3 were detected by immunofluorescence. RESULTS AND CONCLUSION: (1) Compared with the blank control group and the negative control group, the expression of cannabinoid receptor I protein in the cannabinoid receptor I overexpression group was significantly increased, and the difference was significant (P < 0.05). (2) Compared with the blank control group and the negative control group, the proliferation ability of human apical papilla stem cells in the cannabinoid type I overexpression group was the strongest at 5 and 10 days after neural induction (P < 0.05). (3) Compared with the blank control group and the negative control group, the mRNA expression of NeuroD-1, NCAM1, and TH in the stem cells of the human apical papilla in the cannabinoid type I overexpression group was significantly increased, and the fluorescence intensity of Nestin and TUBB3 was significantly enhanced (P < 0.05). (4) Compared with the cannabinoid type I overexpression group, the proliferation ability, mRNA expression level of NeuroD-1, NCAM1, and TH, as well as the fluorescence intensity of Nestin and TUBB3, were significantly decreased in the cannabinoid type I overexpression + AM251 group (P < 0.05). These findings conclude that overexpression of cannabinoid type I promoted the proliferation and neural differentiation of human apical dentin papilla stem cells. Figures and Tables | References | Related Articles | Metrics

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Contribution and interaction of various cells in bone marrow microenvironment to exosomal circular RNA associated with multiple myeloma bone disease Yu Manya, Cui Xing 2026, 30 (1):  101-110.  doi: 10.12307/2025.567 Abstract ( 37 )   PDF (5060KB) ( 44 )   Save BACKGROUND: Multiple myeloma bone disease is a serious complication of multiple myeloma, and its pathogenesis is closely related to the dysregulation of the bone marrow microenvironment. Peripheral blood exosomes are secreted by various cell types and can reflect a variety of information such as the tumor microenvironment. Exosomal circular RNA is gradually becoming the focus of liquid biopsy due to its high stability, high abundance, high specificity, and high conservation. In multiple myeloma bone disease, there is still a lack of relevant research on the role of exosomal circular RNAs. With the development of single-cell RNA sequencing technology, clarifying the contribution of each cell type in the bone marrow microenvironment to multiple myeloma bone disease-related exosomal circular RNAs and the interaction between each cell type will help provide new biomarkers for the diagnosis and treatment of multiple myeloma bone disease. OBJECTIVE: To preliminarily determine which cells in the bone marrow microenvironment the multiple myeloma bone disease-related peripheral blood exosomal circular RNAs originated from, and explore the effects of cell interactions in the bone marrow microenvironment on multiple myeloma bone disease at the single-cell level. METHODS: Peripheral blood exosomes from six multiple myeloma bone disease patients and five healthy controls were collected for high-throughput sequencing, differently expressed circular RNAs were screened, and GO and KEGG enrichment analyses were performed. The bone marrow single-cell RNA sequencing dataset GSE271107 was obtained from the GEO database. The data of four multiple myeloma bone disease patients were integrated. After quality control and filtering, the batch effect was removed by Harmony method. Subgroup clustering was performed by UMAP, and cell groups were manually corrected after automatic annotation by SingleR. CellChat was used to infer and visualize the intercellular communication in single-cell RNA sequencing data, and analyze the interaction between ligands and receptors. RESULTS AND CONCLUSION: (1) Compared with healthy controls, the expression levels of 1 265 circular RNAs in peripheral blood exosomes of multiple myeloma bone disease patients were significantly upregulated. (2) GO and KEGG analyses suggested that the parent genes of differently expressed circular RNAs were mainly enriched in pathways in nervous system development, pathways in cancer, PI3K-Akt signaling pathway, Hippo signaling pathway, arrhythmogenic right ventricular cardiomyopathy, dilated cardiomyopathy, etc., which were closely related to the proliferation, adhesion, migration, and homing of myeloma cells, and multiple myeloma-related complications (such as multiple myeloma bone disease, peripheral neuropathy, and cardiac events). (3) The parent genes of multiple myeloma bone disease-related differential circular RNAs were mainly derived from T cells/natural killer cells, B cells and monocytes/macrophages in the bone marrow microenvironment, which affected osteoclast function by regulating the secretion of multiple cytokines. (4) Monocytes/macrophages, as osteoclast precursor cells, interacted with tumor cells and other immune cells. The MIF pathway was the main pathway involved. The above data preliminarily identified the source cells of multiple myeloma bone disease-related peripheral blood exosomal circular RNA in the bone marrow microenvironment, and found that the ligand-receptor interaction of the MIF pathway between monocytes/macrophages and tumor cells and immune cells may be an important factor in the occurrence of multiple myeloma bone disease. Figures and Tables | References | Related Articles | Metrics

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Effect of fluoride exposure on endoplasmic reticulum-mitochondrial calcium transfer and apoptosis in primary nerve cells Lu Yongheng, Zhu Shuang, Zhao Feiyan, Ai Fujun, Liu Yanjie, Dong Yangting, Guan Zhizhong, Wei Na 2026, 30 (1):  111-119.  doi: 10.12307/2025.929 Abstract ( 28 )   PDF (3109KB) ( 3 )   Save BACKGROUND: Previous studies have found that neuronal damage caused by continuous excessive fluoride exposure is related to Ca2+ overload, but the mechanism of Ca2+ flow conversion between intracellular calcium stores and cell apoptosis damage is still unclear. OBJECTIVE: To investigate the effect of fluoride exposure on Ca2+ transport channel proteins and apoptosis levels in the mitochondria-associated endoplasmic reticulum membrane of primary cultured neural cells.  METHODS: Primary nerve cells of neonatal SD rats were cultured in vitro and identified by immunofluorescence staining with neuronal nucleus-specific antibody up to day 7. The nerve cells were divided into control group (containing 0 mmol/L sodium fluoride), low fluoride group (containing 0.5 mmol/L sodium fluoride), and high fluoride group (containing 1 mmol/L sodium fluoride). The cell morphological changes were observed by light microscope 24 hours after fluorine exposure. The expression levels of apoptosis-related protein BAX/BCL-2 and calcium transfer-related pathways VDAC1, GRP 75, and IP3R were detected using western blot assay. The expression levels of VDAC1, GRP 75, and IP3R mRNA were detected by RT-PCR. Ca2+ levels were detected by Rhood-2AM Ca2+ probe. Mitochondrial membrane potential detection kit was used to detect the change in mitochondrial membrane potential. The level of apoptosis was determined by flow cytometry and TUNEL staining.   RESULTS AND CONCLUSION: (1) The purity of neurons cultured on day 7 had been determined to be over 90%, with few impurities, good growth status, and tight cell network connections, meeting the requirements of subsequent experiments. (2) Compared with the control group, growth of neural cell clusters in the low-fluoride group and the high-fluoride group increased; the processes were broken; the cell body was rounded, and the connection network between cells was destroyed. Compared with the low-fluoride group, the cell damage changes in the high-fluoride group were more obvious. (3) Compared with the control group, the protein expressions of VDAC1, GRP75, and IP3R were increased in the low-fluoride group and the high-fluoride group (P < 0.05), and the ratio of apoptosis-related protein BAX/BCL-2 was increased (P < 0.05). Compared with the control group, the expression of VDAC1 and GRP75 mRNA in the low-fluoride group was significantly increased (P < 0.05); the expression levels of VDAC1, GRP75, and IP3R mRNA in the high-fluoride group were significantly increased (P < 0.01). (4) The level of cell apoptosis increased significantly after fluoride exposure, and the high-fluoride group was significantly higher than the control and low-fluoride groups (P < 0.01). (5) After fluoride exposure, the concentration of mitochondrial Ca2+ in nerve cells increased significantly (P < 0.05), the mitochondrial membrane potential decreased (P < 0.01), and the degree of damage in the high-fluoride group was more obvious (P < 0.05). The results show that fluoride exposure impairs the morphological structure of primary neural cells, resulting in upregulation of Ca2+ transfer pathway protein expression between the endoplasmic reticulum and mitochondria, mitochondrial Ca2+ overload, mitochondrial damage, and increased levels of apoptosis. Figures and Tables | References | Related Articles | Metrics

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Alpha-ketoglutarate engineered small extracellular vesicles delay skin aging Wu Zhijing, Li Jiali, Zhang Jiaxin, Wang Tangrong, Zheng Yuzhou, Sun Zixuan 2026, 30 (1):  120-129.  doi: 10.12307/2026.538 Abstract ( 54 )   PDF (5470KB) ( 39 )   Save BACKGROUND: Cell-free therapy is a research hotspot in the field of medical cosmetic anti-aging. It is still unknown for paracellular secretion of human umbilical cord mesenchymal stem cell-derived small extracellular vesicles loaded with the antiaging drug α-ketoglutaric acid to delay skin aging. OBJECTIVE: To investigate the effect of the anti-aging agent α-ketoglutarate engineered human umbilical cord mesenchymal stem cell-derived small extracellular vesicles in a D-galactose-induced model of dermal fibroblast senescence.  METHODS: (1) Biological characteristics of primary human umbilical cord mesenchymal stem cells were identified by osteogenic-lipogenic differentiation staining and flow cytometry. (2) The small extracellular vesicles derived from human umbilical cord mesenchymal stem cell were obtained by using differential-ultracentrifugation. α-Ketoglutarate-engineered human umbilical cord mesenchymal stem cell-small extracellular vesicles were constructed by electroporation, and biologically characterized by transmission electron microscopy and nanoparticle tracking analyzer, while the encapsulation rate was assessed using high-performance liquid chromatography. (3) The effect of α-ketoglutarate on the proliferative capacity of dermal fibroblasts was assessed by CCK-8 and Edu cell proliferation assay kits. (4) The effect of α-ketoglutarate-engineered human umbilical cord mesenchymal stem cell-small extracellular vesicles on delaying the senescence of dermal fibroblasts was evaluated by reactive oxygen species detection kit, western blot assay, and cellular immunofluorescence.  RESULTS AND CONCLUSION: (1) The obtained human umbilical cord mesenchymal stem cell and human umbilical cord mesenchymal stem cell-small extracellular vesicles were biologically compatible. (2) There was no toxic effect on dermal fibroblasts when α-ketoglutarate was used in the concentration range of 0.5-8 mmol/L. (3) D-gal induced senescence in dermal fibroblasts, while α-ketoglutarate-engineered human umbilical cord mesenchymal stem cell-small extracellular vesicles treatment reduced the level of oxidative stress, DNA damage, and collagen loss, which was further verified that α-ketoglutarate-engineered human umbilical cord mesenchymal stem cell-small extracellular vesicles could effectively slow down the skin aging process. Figures and Tables | References | Related Articles | Metrics

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Choline kinase alpha silencing affects proliferation and apoptosis in glioma cells by inducing mitochondrial dysfunction Zhao Yang, Li Jialin, Wu Xiao, Zou Yourui, Liu Yang, Ma Hui 2026, 30 (1):  130-138.  doi: 10.12307/2026.540 Abstract ( 31 )   PDF (2423KB) ( 8 )   Save BACKGROUND: Choline kinase alpha is a key enzyme in phospholipid metabolism, involved in the synthesis of phosphatidylcholine, and plays an important role in maintaining cell membrane integrity and signal transduction. Research has shown that choline kinase alpha is highly expressed in various tumors and is closely related to cell proliferation, metabolic reprogramming, and tumor progression. As a potential therapeutic target, the role of choline kinase alpha in tumor metabolism and mitochondrial function still needs further exploration.  OBJECTIVE: To evaluate the effects and the underlying mechanisms of choline kinase alpha on the proliferation and apoptosis of glioma U87MG and U251 cells.  METHODS: Short hairpin RNA of choline kinase alpha and its empty vector control were transfected into U87MG and U251 glioma cells. Mitochondrial morphology was observed by transmission electron microscopy. Mitochondrial structure and functional protein levels were assessed by western blot assay. Reactive oxygen species levels in cells were measured using a reactive oxygen species fluorescent probe. Mitochondrial membrane potential was assessed with a JC-1 assay. Intracellular adenosine triphosphate levels were measured by chemiluminescence. Cell proliferation was evaluated using a CCK-8 assay. Apoptosis levels were analyzed by flow cytometry. The mitochondrial fission inhibitor Mdivi-1 was used to protect the mitochondrial function of the choline kinase α-silenced lentiviral cells. Finally, U87MG cells were subcutaneously injected to construct a subcutaneous tumor model in nude mice. The tumor growth in nude mice was observed before and after choline kinase alpha silencing and after the use of the mitochondrial fission inhibitor Mdivi-1.  RESULTS AND CONCLUSION: (1) Compared with the empty control group, the mitochondria of U87MG and U251 cells in the choline kinase alpha silencing lentivirus group exhibited significant structural abnormalities in mitochondria, such as vacuolization and cristae disruption. The expressions of mitochondrial structure and function-related proteins TOM20, ACO2, and ATP5A were significantly decreased (P < 0.01, P < 0.001), the expression of SOD2 was significantly increased (P < 0.01, P < 0.000 1), the fluorescence intensity of reactive oxygen species was significantly increased (P < 0.01), the mitochondrial membrane potential and adenosine triphosphate level were significantly decreased (P < 0.01, P < 0.001), the cell proliferation ability was reduced (P < 0.01), and the apoptosis level was increased (P < 0.001). (2) Following Mdivi-1 treatment, the fluorescence intensity of reactive oxygen species in U87MG and U251 cells decreased (P < 0.05, P < 0.01), mitochondrial membrane potential and adenosine triphosphate levels were significantly restored (P < 0.05, P < 0.01, P < 0.001), cell proliferation ability was improved (P < 0.05, P < 0.01), and apoptosis level was decreased (P < 0.05). (3) In addition, the in vitro subcutaneous tumor formation experiment of nude mice showed that compared with the empty control group, the mass and growth rate of subcutaneous tumors formed by U87MG cells in the choline kinase alpha silencing lentivirus group were significantly reduced (P < 0.000 1). After Mdivi-1 treatment, the mass and growth rate of tumors were significantly increased (P < 0.000 1). (4) The results show that choline kinase alpha silencing affects the proliferation and apoptosis of glioma cells by inducing mitochondrial dysfunction. Figures and Tables | References | Related Articles | Metrics

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Relationship between BCR/ABL gene expression and recurrence before and after allogeneic transplantation in Ph chromosome positive acute lymphoblastic leukemia Xue Hui, Li Dongnan, Zhao Yadi, Chen Chao, Xie Zongyuan 2026, 30 (1):  139-144.  doi: 10.12307/2026.025 Abstract ( 35 )   PDF (776KB) ( 1 )   Save BACKGROUND: BCR/ABL gene is a specific gene of Ph chromosome-positive acute lymphoblastic leukemia, and its expression level has become a sensitive indicator for monitoring minimal residual disease before and after allogeneic hematopoietic stem cell transplantation. However, whether the expression level of BCR/ABL gene before transplantation affects the efficacy of transplantation and how to guide the early intervention of relapse with tyrosine kinase inhibitors after transplantation is still inconclusive. OBJECTIVE: To explore the relationship between BCR/ABL gene expression and recurrence in patients with Ph chromosome positive acute lymphoblastic leukemia before and after related and allogeneic hematopoietic stem cell transplantation. METHODS: Twenty-four patients with Ph chromosome positive acute lymphoblastic leukemia who achieved complete hematological remission and underwent allogeneic hematopoietic stem cell transplantation were selected at the Affiliated Hospital of North China University of Science and Technology between January 2015 and December 2022. Real time fluorescence quantitative polymerase chain reaction was used to dynamically detect the expression levels of BCR/ABL genes during treatment, representing minimal residual disease. Based on BCR/ABL gene expression, tyrosine kinase inhibitors combined with chemotherapy was administered before transplantation to select the timing of allogeneic hematopoietic stem cell transplantation. After transplantation, the disease status was evaluated to guide the use of tyrosine kinase inhibitors, and an early intervention plan for recurrence was developed.  RESULTS AND CONCLUSION: Follow-up was until December 2023, with a median follow-up time of 49 (12-82) months. There were 8 cases of hematological recurrence, with a median recurrence time of 14 (8-39) months and a cumulative recurrence rate of 33% (8/24). Univariate analysis showed that recurrence after allogeneic hematopoietic stem cell transplantation was not significantly correlated with gender, age, extramedullary complications, time from diagnosis to transplantation, HLA typing, acute graft-versus-host disease, and chronic graft-versus-host disease (P > 0.05). There was a significant correlation between the relief treatment course and minimal residual disease levels before transplantation. The second hematology completely resolution and positive minimal residual disease before transplantation had a higher hematological recurrence rate (P < 0.05). The 3-year cumulative recurrence rate, disease-free survival rate, and overall survival rate were 27%, 63%, and 74%; the 5-year cumulative recurrence rate, disease-free survival rate, and overall survival rate were 38%, 57%, and 74%, respectively. It is concluded that Ph chromosome positive acute lymphoblastic leukemia patients with BCR/ABL gene positive before transplantation have a higher recurrence rate. BCR/ABL gene expression after transplantation can guide the application of tyrosine kinase inhibitors and serve as a basis for early intervention in recurrence. Figures and Tables | References | Related Articles | Metrics

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Regulation of lysosome function by stem cells in treatment of lysosomal storage diseases Li Yiwen, Liu Feixiang, Zhang Yunke 2026, 30 (1):  145-152.  doi: 10.12307/2026.508 Abstract ( 33 )   PDF (984KB) ( 10 )   Save BACKGROUND: Lysosomal storage diseases, as a group of rare genetic metabolic disorders, exhibit complex pathogenesis often leading to dysfunction of cells, tissues, and organs. Current therapeutic approaches have certain limitations. Stem cell transplantation, as an emerging treatment method, offers new options for patients with lysosomal storage diseases. OBJECTIVE: To review the mechanisms of action of stem cells in regulating lysosomes for the treatment of lysosomal storage diseases and explore the feasibility of traditional Chinese medicine in treating such diseases, providing new insights for the treatment of lysosomal storage diseases with stem cells.  METHODS: Relevant literature from 2010 to 2024 was searched in CNKI and PubMed databases using keywords “stem cells, lysosomal storage disease, lysosome” in English and Chinese. Ultimately, 78 articles were included for review and analysis.  RESULTS AND CONCLUSION: (1) Stem cells treat lysosomal storage diseases by regulating lysosomes primarily through three aspects: regulating stem cell differentiation and replacement, improving intercellular communication and the microenvironment, and enhancing lysosomal enzyme expression through gene editing. (2) Stem cells have achieved significant effects in the treatment of some lysosomal storage diseases, such as Niemann-Pick disease, mucopolysaccharidoses, Gaucher disease, and metachromatic leukodystrophy. (3) The procedure for stem cell transplantation needs further optimization. Adverse reactions post-transplantation urgently need to be addressed, and the efficiency and safety of gene-modified stem cells also need to be further improved. In the future, more research on the treatment of lysosomal storage diseases with traditional Chinese medicine is required to reveal the relevant mechanisms for the treatment of lysosomal storage diseases with traditional Chinese medicine.  Figures and Tables | References | Related Articles | Metrics

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Application and progress of dental pulp stem cells and their derivatives in dental pulp regeneration Xu Haichao, Luo Lihua, Pan Yihuai 2026, 30 (1):  153-162.  doi: 10.12307/2025.572 Abstract ( 42 )   PDF (1109KB) ( 4 )   Save BACKGROUND: Dental pulp stem cells, which derived from the dental pulp tissue, are one type of dental-derived mesenchymal stem cells, possess significant properties of self-renewal and multi-lineage differentiation. In recent years, series of researches focus on dental pulp stem cells and their derivatives such as extracellular vesicles, conditioned medium, and decellularized extracellular matrix, those have positive effects on the repair and regeneration of pulp tissue injury, showing an attractive clinical application.   OBJECTIVE: To systematically review the researches and applications of dental pulp stem cells and their derivatives in dental pulp tissue engineering.   METHODS: Literature searches were conducted in PubMed, China Biology Medicine (CBM), and China National Knowledge Infrastructure (CNKI) databases for articles published from January 2005 to June 2023. The search terms included “dental pulp stem cells, extracellular vesicles, exosomes, apoptotic bodies, conditioned medium, decellularized matrix, regeneration” in Chinese and English. After screening the titles and abstracts, duplicate and irrelevant studies were excluded. Finally, 103 studies closely related to dental pulp regeneration were included for review and analysis.   RESULTS AND CONCLUSION: Dental pulp stem cells and their derivatives are rich in lots of bioactive factors that can effectively promote odontogenic, angiogenic, and neurogenic differentiation, exhibiting significant potential in the formation of the pulp-dentin complex. However, the clinical translation of dental pulp stem cells and their derivatives still faces several challenges. Future researches should focus on optimizing preparation protocols, elucidating the underlying mechanisms of action, and refining safety assessments to provide novel therapeutic strategies for the repair of dental pulp injury. Figures and Tables | References | Related Articles | Metrics

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Therapeutic potential of bioactive substances secreted by dental mesenchymal stem cells for bone repair Zhang Zhaowei, Chen Ouzile, Bai Mingru, Wang Chenglin 2026, 30 (1):  163-174.  doi: 10.12307/2025.571 Abstract ( 34 )   PDF (1896KB) ( 5 )   Save BACKGROUND: Dental mesenchymal stem cells are considered a promising source for bone tissue repair due to their high proliferation potential, osteogenic differentiation capacity, and immunomodulatory properties. However, some allogeneic applications of stem cells still have potential carcinogenic effects and immune rejection risks. Recently, studies have highlighted the paracrine effects mediated by secretions from dental mesenchymal stem cells in bone tissue repair. These secretions include the soluble factors and extracellular vesicles. OBJECTIVE: To review the research progress of dental mesenchymal stem cells in repairing bone defects through paracrine effects. METHODS: Using search terms “dental mesenchymal stem cell, paracrine, osteogenesis, conditioned medium, extracellular vesicle” in Chinese and English, relevant literature published between 2019 and 2024 was retrieved from databases including CNKI, PubMed, and Elsevier ScienceDirect. A total of 104 studies were ultimately selected for this review.  RESULTS AND CONCLUSION: (1) Dental mesenchymal stem cells-conditioned medium contains multiple bioactive factors beneficial for bone repair. These factors directly promote bone formation through regulatory agents such as osteocalcin, osteopontin, bone morphogenetic protein, and dentin sialophosphoprotein. They also play an indirect promoting role in bone tissue repair through neurotrophic factors, vascular endothelial growth factor, and immunomodulatory and anti-inflammatory agents. (2) Dental derived mesenchymal stem cell-derived extracellular vesicles not only contain some cytokines from dental conditioned medium, but also various miRNAs, which promote bone repair by directly promoting osteogenesis, angiogenesis, regulating immune cells, and inflammation control. These extracellular vesicles can be engineered within different scaffold materials to achieve controlled or sustained release, enhancing therapeutic efficacy.  Figures and Tables | References | Related Articles | Metrics

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Stem cell exosomes and biomaterial-assisted exosomes in bone defect repair Liu Nian, Dong Xinyue, Wang Songpeng, Xu Yingjiang, Zhang Xiaoming 2026, 30 (1):  175-183.  doi: 10.12307/2025.569 Abstract ( 24 )   PDF (1032KB) ( 3 )   Save BACKGROUND: A large number of studies have demonstrated that stem cell exosomes play an important role in the repair of bone defects, either directly as carriers for loading other small molecules or surface modifications, or by binding to biomaterials to promote the repair and regeneration of bone tissue. OBJECTIVE: To summarize the osteogenic mechanisms of stem cell exosomes from different sources and their research progress in bone defect repair.  METHODS: Chinese search terms “stem cell, exosome, bone, biomaterial, carrier, bioceramic, polymer, metal, hydrogel, engineered exosome” were used to search CNKI. English search terms “stem cell, exosome, bone defect, biomaterial, carrier, bioceramic, ploymer, metal material, hydrogel, engineering exosome” were used to search PubMed database. According to the inclusion and exclusion criteria, 77 relevant articles were finally included for summary. RESULTS AND CONCLUSION: Exosomes from stem cells of different origins can promote osteoblast proliferation and differentiation, promote angiogenesis, and regulate osteoclast activity and macrophage phenotype to promote bone formation and bone mineralization. In addition, many achievements of exosomes in the field of bone defect repair were described from two aspects: biomaterial-assisted exosomes and engineered exosomes. However, the current research on stem cell exosomes in bone tissue engineering is still insufficient, and most of these studies are limited to small animal models, while the treatment of bone defects in large animals, including humans, will be more complex, which will also become a major challenge for the treatment of bone defects. This will also be a great challenge in the dissemination of exosome therapy. Figures and Tables | References | Related Articles | Metrics

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Regulatory mechanisms of exosome secretion and its application prospects in biomedicine Lyu Ruyue, Gu Lulu, Liu Qian, Zhou Siyi, Li Beibei, Xue Letian, Sun Peng 2026, 30 (1):  184-193.  doi: 10.12307/2025.573 Abstract ( 43 )   PDF (1846KB) ( 6 )   Save BACKGROUND: Exosomes, as a type of extracellular vesicle, have become a key medium for cell-to-cell communication due to their nanoscale size and enrichment of various bioactive substances. The study of exosome secretion regulation not only has important scientific value, but also has broad application prospects in clinical practice, and is of great significance for promoting medical progress and improving human health.  OBJECTIVE: To review the biological characteristics, biological functions, biogenesis process and biochemical regulation mechanism of exosomes, and to explore the application prospects of exosomes in disease diagnosis, treatment and vaccine development, so as to provide theoretical basis and reference for basic research and clinical transformation of exosomes. METHODS: The first author searched PubMed and CNKI databases in October 2024 for relevant literature published from January 2010 to October 2024. Key words were “exosomes, biological functions, biogenesis, secretion or release, regulatory mechanisms, application prospects” in Chinese and English. Finally, 92 articles were included for analysis.  RESULTS AND CONCLUSION: The secretion level of exosomes can be regulated through physical or biochemical means. Exosomes show broad application prospects in the fields of disease diagnosis, treatment, and vaccine development, and may play a key role in the treatment of cardiovascular and cerebrovascular diseases as well as cancer. This review provides valuable information for the clinical translation and application research of exosomes, helping to promote future progress in exosome research and application. Figures and Tables | References | Related Articles | Metrics

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Isolation, identification, and application of exosomes derived from mesenchymal stem cells Liu Yu, Gong Senyi, Yang Lihua, Li Weifeng, Hu Yuwen, Yan Qinbiao, Guo Meijin 2026, 30 (1):  194-203.  doi: 10.12307/2025.570 Abstract ( 37 )   PDF (1607KB) ( 12 )   Save BACKGROUND: Exosomes derived from mesenchymal stem cells play pivotal roles in cell communication and epigenetic regulation due to their low immunogenicity and targeted delivery effects, and have been clinically applied in the treatment of various diseases.  OBJECTIVE: To review the isolation, purification, identification methods, and application progress of mesenchymal stem cell-derived exosomes, and to facilitate the development of large-scale preparation techniques and clinical translation of mesenchymal stem cell-derived exosomes.  METHODS: The Chinese search terms “exosome, mesenchymal stem cells, isolation, purification, characterization, clinical application” and the English search terms “exosome, extracellular vesicles, mesenchymal stem cells, isolation, characterization, application” were used to search the literature published before September 2024 in CNKI, PubMed, and Web of Science databases. Articles with poor relevance to the topic, outdated, or duplicated content were excluded, and finally, 109 articles were included for review. RESULTS AND CONCLUSION: (1) This paper reviews recent methods for isolating and purifying exosomes, comparing the characteristics of ultracentrifugation, ultrafiltration, size-exclusion chromatography, polymer precipitation, immunoaffinity, microfluidic methods, and other novel approaches based on their underlying principles. (2) Methods for identifying exosomes can be categorized into physical and biochemical analyses, characterizing exosomes based on their shape, size, and characteristic proteins. (3) Mesenchymal stem cell-derived exosomes have broad applications in multiple fields such as medical aesthetics, wound repair, and cancer treatment, due to their immune-regulatory properties and ability to cross biological barriers. (4) The clinical translation of exosomes faces challenges due to their complex structure, lack of universal isolation techniques, and poor stability, making it difficult to achieve in a short period of time. Figures and Tables | References | Related Articles | Metrics

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Engineered exosomes for repairing tissue damage: application potential, excellent biological stability, and targeting specificity Luo Wenbin, Li Ruoyun, Pan Chaofan, Luo Changjiang 2026, 30 (1):  204-217.  doi: 10.12307/2025.543 Abstract ( 45 )   PDF (1289KB) ( 4 )   Save BACKGROUND: Exosomes are nanoscale extracellular vesicles secreted by various types of cells, with advantages such as high bioavailability, low toxicity, low immunogenicity, and good biocompatibility. However, natural exosomes have certain limitations in clinical therapy. By using bioengineering techniques to modify and engineer exosomes, the engineered exosomes not only improve their original therapeutic effects but also exhibit excellent biostability and targeting specificity, showing great potential for application in the field of tissue repair. OBJECTIVE: To summarize the various strategies for engineering exosomes, including functional loading and surface modification, outline the research progress of engineered exosomes in different tissue repairs, and explore the therapeutic potential of engineered exosomes in tissue repair. METHODS: PubMed database was searched for relevant literature published between 2010 and 2024 using the search terms “engineered exosomes, tissue repair, biomaterials, tissue engineering, wound healing, parenchyma, bone regeneration, cartilage, neural, myocardial, hepatic.” Studies that were not closely related to the article’s theme, of poor quality, repetitive, or outdated were excluded. A total of 115 articles met the inclusion criteria. RESULTS AND CONCLUSION: (1) Functional loading is used to combine therapeutic molecules with exosomes to obtain additional properties or to enhance the original physiological function of the exosome, among which ultrasonication and extrusion are simple to operate and can obtain higher drug loading capacity at the same time. (2) Surface modification can make exosomes express desired proteins or enhance their targeting, including genetic engineering and chemical modification. Genetic engineering is complicated, poorly reproducible, and the end product is poorly controllable. Chemical modification, on the other hand, is relatively simple and versatile, and is more suitable for designing highly targeted and functionally specific engineered exosomes. (3) Among the techniques for pre-treating cells to obtain engineered exosomes, hypoxic pre-treatment is more widely used because of its simplicity and clearer mechanism, which can activate glycolysis to promote cell proliferation, and regulate the vascular endothelial growth factor receptor signaling pathway through the generation of hypoxia-inducible factors to promote angiogenesis. (4) The function of exosomes is affected by various factors such as cell source, cell state, synthesis process, and extracellular environment. If the engineering strategy is complicated, it is more difficult to ensure the functional consistency of the final engineered exosomes, so the relatively simple and reliable engineering strategy is more suitable for its clinical application. (5) Engineered exosomes combined with biomaterials or scaffolds can be used to treat complex wounds of skin soft tissue, such as infected wounds and diabetic ulcers. This approach enhances exosome delivery and controls their release, promotes tissue repair, controls infection, and regulates the local microenvironment of the wound. (6) A single mechanism of engineered exosomes is often ineffective due to the specificity of the bone tissue fracture, so dual or even multi-functional engineered exosomes are needed to promote fracture repair while anti-inflammatory or remodeling the vascular system. (7) The source of exosomes has a significant impact on neural tissue repair. Exosomes derived from different neural cells promote neural repair through different effects. In addition, the combination of stents and engineered exosomes for traumatic brain injury has obvious advantages, the stent itself provides hemostasis and support, combined with the engineered exosomes itself to promote the repair effect, can obtain better therapeutic effect. (8) In cardiac and hepatic tissue repair, it is needed to develop anti-fibrotic engineered exosomes to resist the abnormal repair of cardiac and hepatic tissues themselves, which will require further research in the future.  Figures and Tables | References | Related Articles | Metrics

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Role of extracellular vesicle-mediated intercellular communication in female follicle reproduction, preimplantation embryo development and implantation Liu Jing, Zhao Xiaoli, Xia Tian 2026, 30 (1):  218-228.  doi: 10.12307/2025.554 Abstract ( 32 )   PDF (1179KB) ( 2 )   Save BACKGROUND: Extracellular vesicles mediate intercellular signal transduction through the proteins, nucleic acids, and lipids they carry, thereby influencing the function of target cells. This vesicle-mediated communication mechanism is involved in regulating female reproductive development. OBJECTIVE: To summarize and analyze the regulatory roles of extracellular vesicle-mediated intercellular communication in female reproductive development. METHODS: A search was conducted in the PubMed database using the search terms “extracellular vesicles, exosomes, reproduction, maternal-embryo communication, maternal-fetal crosstalk, embryo implantation, endometrium, oviduct, follicle.” The initial screening was carried out by reading the titles and abstracts of the literature, and then the literature with poor relevance to the research purpose, outdated content, and duplication was excluded according to the inclusion and exclusion criteria. Ultimately, 69 relevant articles were included for comprehensive analysis. RESULTS AND CONCLUSION: Extracellular vesicles play a crucial role in key processes of female reproductive development, from folliculogenesis to implantation. (1) Extracellular vesicles mediate intercellular communication within the follicle, particularly the interactions between oocytes and follicular cells, which are essential for follicle development and maturation. (2) Extracellular vesicles and their contents facilitate interactions between the embryo and the fallopian tube, influencing the trajectory of embryonic development. (3) Extracellular vesicles and their contents promote implantation by mediating bidirectional communication between the embryo and the endometrium. Uterine-derived extracellular vesicles regulate processes such as embryo adhesion, invasion, and decidualization, while embryo-derived extracellular vesicles modulate endometrial receptivity, convey embryonic signals, and adjust the endometrial microenvironment. Studying the roles of extracellular vesicles in female reproductive development can provide valuable insights into the mechanisms of infertility and support the development of new therapeutic strategies.  Figures and Tables | References | Related Articles | Metrics

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Advances and application of neutrophil extracellular traps and activated platelets in lung cancer research Yu Daiyao, Shi Ping, Yang Lan, Li Zhishu, Lu Yongping 2026, 30 (1):  229-237.  doi: 10.12307/2025.580 Abstract ( 33 )   PDF (1452KB) ( 3 )   Save BACKGROUND: Neutrophil extracellular traps and activated platelets are involved in the invasion, metastasis, growth, and angiogenesis of lung cancer, and are closely related to the development and prognosis of lung cancer. OBJECTIVE: To review the mechanism of neutrophil extracellular traps and activated platelets in lung cancer and their application in diagnosis, prognosis, and treatment of lung cancer. METHODS: “Platelet activation, lung neoplasms, extracellular traps, treatment” for English search terms and “lung cancer, neutrophil-extracellular traps, platelet activation, P-selectin, treatment” for Chinese search terms were searched in PubMed and CNKI databases. After reading the title and abstract of the literature, according to the inclusion and exclusion criteria, 63 articles with high relevance were finally included. RESULTS AND CONCLUSION: (1) Formation of neutrophil extracellular traps and platelet activation were induced by lung tumor. (2) Neutrophil extracellular traps and activated platelets jointly promote the proliferation, growth and metastasis of lung cancer. (3) Neutrophil extracellular traps can be used as a novel biomarker for the diagnosis, prognosis and progression of lung cancer. (4) Targeting neutrophil extracellular traps and activating platelets can be used as potential therapies for lung cancer.   Figures and Tables | References | Related Articles | Metrics

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Intestinal organoids: a bibliometric analysis of the latest trends in tissue/organ biology, disease modeling, and clinical applications Zhao Qianwei, Sun Guangyuan 2026, 30 (1):  238-247.  doi: 10.12307/2026.542 Abstract ( 34 )   PDF (3550KB) ( 15 )   Save BACKGROUND: Intestinal organoids are highly attractive in tissue/organ biology, disease modeling, and clinical applications, and have become one of the frontiers of biomedical research in recent years. However, this emerging field has not yet been summarized by bibliometrics. OBJECTIVE: To summarize the research trends of intestinal organoids and explore the hot topics and frontier advances of intestinal organoids based on bibliometrics.  METHODS: Relevant literature on intestinal organoids was retrieved from the Web of Science Core Collection database, spanning the period from January 1, 2006 to November 6, 2024. CiteSpace, VOSviewer, and Office software was utilized to conduct bibliometric and visual analyses of the retrieved literature, focusing on annual publication volume, countries, institutions, authors, journals, citations, and keywords. RESULTS AND CONCLUSION: A total of 2 135 articles were retrieved, and after rigorous screening, 1 577 articles were included in the final analysis. From 2006 to 2024, there was a steady increase in global publications in the field of intestinal organoids. Molecular biology, genetics, immunology, and clinical medicine emerged as the mainstream disciplines in intestinal organoid research. The United States had the highest number of publications in the field of intestinal organoids and maintained close collaborations with countries such as China, the Netherlands, and Germany. Utrecht University in the Netherlands was the most prolific institution, while the International Journal of Molecular Sciences was the journal with the highest number of publications in the area of intestinal organoids. The article “Replication of human noroviruses in stem cell-derived human enteroids” had the highest co-citation frequency. Human intestinal organoids, stem cell niches, and the potential of organoid therapy are the frontiers and hotspots in the domain of intestinal organoids. The integration of organoids with bioengineering and material technology, as well as intestinal organoid-on-a-chip technology, represent future research priorities in this field. This article provides a comprehensive overview of intestinal organoid research using bibliometric and visualization methods. This paper will help scholars to better understand the dynamic evolution of intestinal organoids and provide guidance for future research. Figures and Tables | References | Related Articles | Metrics

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Targeting diverse chimeric antigen receptor T cell-related targets in treatment of B-cell hematological malignancies: a review of long-term follow-up data Xu Fanping, Li Qinchun, Tang Dongfang 2026, 30 (1):  248-259.  doi: 10.12307/2025.565 Abstract ( 39 )   PDF (1325KB) ( 8 )   Save BACKGROUND: Chimeric antigen receptor T cell therapy is a cutting-edge approach for the treatment of B cell hematological malignancies. These cells efficiently and specifically recognize and kill tumor cells, unrestricted by major histocompatibility complex limitations. OBJECTIVE: To elucidate the structure, developmental history, and marketed progress of chimeric antigen receptor T cells, summarize their long-term efficacy in B cell hematological malignancies treatments, and discuss associated toxicities, recurrence, and mitigation strategies. Additionally, it reviews the advancement of potential targets in B cell hematological malignancies treatments. METHODS: Searches were conducted in PubMed, CNKI, and WanFang databases using the terms “CAR-T, B cell hematological malignancies, toxic side effects, immunotherapy” in Chinese and English, focusing on articles regarding chimeric antigen receptor T cell targets in B-cell malignant tumor treatments. RESULTS AND CONCLUSION: (1) The U.S. Food and Drug Administration and National Medical Products Administration have approved 11 chimeric antigen receptor T cell products, primarily targeting CD19 and B cell maturation antigen targets in B cell hematological malignancies. (2) Long-term follow-up data indicate that chimeric antigen receptor T cell therapy provides a high remission rate and enduring responses in B cell hematological malignancies patients, albeit with recurrence issues due to antigen loss or downregulation. (3) Chimeric antigen receptor T cell therapy is associated with significant toxicities, a high recurrence rate, and drug resistance, constraining its broad application. (4) Future research should concentrate on developing new targets, combined therapies, and strategies to enhance chimeric antigen receptor T cell persistence and antitumor activity. Figures and Tables | References | Related Articles | Metrics

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Instructions for Authors - Chinese Journal of Tissue Engineering Research (CJTER) 2026, 30 (1):  260-267.  doi: 10.12307/2026.050 Abstract ( 22 )   PDF (744KB) ( 2 )   Save Related Articles | Metrics