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08 January 2022, Volume 26 Issue 1 Previous Issue    Next Issue

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Hypoxic pretreatment enhances the protective effect of aged human bone marrow mesenchymal stem cells conditioned medium against H9C2 oxidative stress damage Song Huifang, Tan Jiayin, Kang Yi, Li Bin, Bi Zhifei, Long Nü, Xia Zhongnian, Guo Rui 2022, 26 (1):  1-6.  doi: 10.12307/2022.001 Abstract ( 661 )   PDF (1241KB) ( 450 )   Save BACKGROUND: The therapeutic effect of autologous stem cell transplantation in aged patients suffered with ischemic heart injury is not good as young. It is important to explore effective methods to improve the repair and regenerate ability of aged stem cells.  OBJECTIVE: To investigate the protective effect of hypoxia preconditioning aged human bone marrow mesenchymal stem cells conditioned medium on myocardium and to provide experimental support for more effective autologous stem cell transplantation in aged patients.  METHODS: The young human bone marrow mesenchymal stem cells were placed in a normoxic incubator, and the aged human bone marrow mesenchymal stem cells were placed in a normoxic or hypoxic incubator respectively. The culture media were collected and divided into three groups: norCM-young, norCM-old and hypoCM-old. H9C2 cells were treated with three groups of conditioned media, and then treated with 300 μmol/L H2O2 for 30 minutes to establish an oxidative stress model. The cell survival rate of H9C2 was detected by the CCK-8 assay. Reactive oxygen species level detection by reactive oxygen species assay kit reflected the degree of oxidative stress damage. Bax and Bcl-2 expression levels by western blotting reflected the apoptosis level. p-AKT expression level detected by western blot assay reflected AKT activation level. In addition, H9C2 was cultured with Dulbecco’s Modified Eagle Medium containing 50 μmol/L LY294002 for 2 hours before hypoCM-old and H2O2 treatment to block the PI3K/AKT pathway and cell viability was detected by the CCK-8 assay.   RESULTS AND CONCLUSION: (1) Compared with norCM-old group, hypoCM-old significantly improved the survival rate of H9C2 cells under oxidative stress damage (P < 0.01); significantly reduced the expression of apoptosis-related protein Bax (P < 0.05), increased the expression of apoptosis inhibitor protein Bcl-2 (P < 0.05); and reduced the ROS level in H9C2 cells (P < 0.05). (2) Compared with the norCM-old group, the p-AKT protein level in H9C2 cells treated with hypoCM-old was significantly increased (P < 0.05). (3) Compared with the hypoCM-old group, when the PI3K/AKT pathway of H9C2 was inhibited, the H9C2 cell survival was reduced (P < 0.05). (4) The results indicate that the conditioned media of aged human bone marrow mesenchymal stem cells pretreated with hypoxia could attenuate the oxidative stress damage of H9C2 cells, reduce apoptosis and enhance survival through the activation of AKT pathway.  Figures and Tables | References | Related Articles | Metrics

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Influence of related factors on the first results of peripheral blood hematopoietic stem cell mobilization in lymphoma patients Guo Qiuxia, Wang Jigang 2022, 26 (1):  7-11.  doi: 10.12307/2022.002 Abstract ( 501 )   PDF (1134KB) ( 94 )   Save BACKGROUND: The effect of hematopoietic stem cell collection is affected by a variety of factors, but the clear influencing factors have not yet been determined. It is necessary to continuously explore the risk factors that may affect the collection of hematopoietic stem cells. OBJECTIVE: To investigate the influence of related factors on the first results of hematopoietic stem cell mobilization in peripheral blood of 50 patients with malignant lymphoma, and to explore the relationship between results and hematopoietic reconstruction after transplantation.  METHODS: Totally 50 lymphoma patients undergoing autologous peripheral blood hematopoietic stem cell transplantation from January 2015 to January 2020 were included in this study so as to analyze the age, stage, bone marrow invasion, recurrence, radiotherapy, granulocyte colony-stimulating factor duration, chemotherapy duration and other factors on the first hematopoietic stem cell collection, and to explore the relationship of collection results with neutrophile granulocyte and platelet implantation.  RESULTS AND CONCLUSION: The number of chemotherapy courses was negatively correlated with the collected CD34+ cell count. The results of hematopoietic stem cell collection were poor in patients with recurrence before transplantation, and among the radiotherapy patients, mobilization failure was relatively high, with a failure rate of 88.9%. Radiotherapy had a negative effect on hematopoietic stem cell collection. The higher the CD34+ cell count, the faster the neutrophile granulocyte implantation. However, the effect on post-transplantation platelet implantation was not so significant, but there was a trend. There was no difference in the number of CD34+ cells collected between granulocyte colony-stimulating factor duration of 1-5 days and granulocyte colony-stimulating factor duration of over 5 days. The results concluded that in lymphoma patients, excessive chemotherapy, recurrence and radiotherapy experience will obviously cause damage to hematopoietic stem cells. Radiotherapy should be performed after hematopoietic stem cell collection to avoid damage to hematopoietic stem cells. Figures and Tables | References | Related Articles | Metrics

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Hyperbaric oxygen combined with NgR gene silencing bone marrow mesenchymal stem cells transplantation for spinal cord injury in rats Mei Yunyun, Zhang Jianjun, Wang Dong 2022, 26 (1):  12-19.  doi: 10.12307/2022.003 Abstract ( 543 )   PDF (3908KB) ( 273 )   Save BACKGROUND: Hyperbaric oxygen therapy and inhibition of Nogo-A/NgR-RhoA/ROCK signaling pathways are conducive to the proliferation and differentiation of transplanted cells. OBJECTIVE: To explore the effects of hyperbaric oxygen plus rat bone marrow mesenchymal stem cells transplantation carrying miRNA silencing NgR gene on repair of rat spinal cord injury. METHODS: Rat bone marrow mesenchymal stem cells were transfected using constructed miRNA recombinant plasmid targeting NgR. The expression levels of NgR were detected by real-time quantitative PCR and western blot assay after transfection. The 15 of 80 Sprague-Dawley rats were randomly selected as sham group and the remaining 65 rats were used to construct models of spinal cord injury; and 60 successful models were randomly divided into spinal cord injury group, hyperbaric oxygen group, rat bone marrow mesenchymal stem cells group and rat bone marrow mesenchymal stem cells plus hyperbaric oxygen group. The rat bone marrow mesenchymal stem cells group and hyperbaric oxygen plus rat bone marrow mesenchymal stem cells group were injected with 5 μL rat bone marrow mesenchymal stem cells suspension (5×106 cells) after 24 hours, respectively, and the spinal cord injury and hyperbaric oxygen groups were injected with PBS of the same volume. The hyperbaric oxygen and hyperbaric oxygen plus rat bone marrow mesenchymal stem cells group received continuous treatment for 7 days. The hind limb motor function was evaluated by Basso Beattie Bresnahan score before and after the modeling, once a week, for 4 consecutive weeks. After 4 weeks of modeling, somatosensory evoked potential testing was performed to detect the recovery of neural conduction. The histopathological damage, apoptosis of cells and axon regeneration in spinal cord tissues was observed by hematoxylin-eosin staining, TUNEL staining and fluorescent gold retrograde tracing, respectively. After hyperbaric oxygen therapy, the mRNA relative expression levels of Nogo-A, NgR, RhoA, ROCK-1, Lingo-1 and p75NTR were detected by real-time quantitative PCR around the injured region.    RESULTS AND CONCLUSION: (1) An obvious decrease was found in NgR expression levels after rat bone marrow mesenchymal stem cells transfection. (2) Basso Beattie Bresnahan score of 2 to 4 weeks after modeling: hyperbaric oxygen plus rat bone marrow mesenchymal stem cells group > rat bone marrow mesenchymal stem cells group and hyperbaric oxygen group > spinal cord injury group (P < 0.05). (3) The latency of somatosensory evoked potential was shortened and the amplitude of somatosensory evoked potential was increased in hyperbaric oxygen plus rat bone marrow mesenchymal stem cells group compared with other treatment groups (P < 0.05). There was no significant difference in latency and amplitude of somatosensory evoked potential between the rat bone marrow mesenchymal stem cells group and the hyperbaric oxygen group (P > 0.05). (4) Compared with the spinal cord injury group, the number of neurons increased; the number of axons increased; the regeneration effect of neurons was obvious and the apoptosis was reduced in the hyperbaric oxygen group and rat bone marrow mesenchymal stem cells group. The repair effect was better in the hyperbaric oxygen plus rat bone marrow mesenchymal stem cells group than that in other two treatment groups. (5) The mRNA relative expression of Nogo-A/NgR/RhoA-ROCK signaling pathway was significantly inhibited in hyperbaric oxygen plus rat bone marrow mesenchymal stem cells group, rat bone marrow mesenchymal stem cells group and hyperbaric oxygen group compared with the spinal cord injury group, but there was no significant difference between hyperbaric oxygen group and rat bone marrow mesenchymal stem cells group (P > 0.05). (6) In summary, hyperbaric oxygen combined with NgR gene silencing rat bone marrow mesenchymal stem cells transplantation can inhibit the gene expression of Nogo-A/NgR/RhoA-ROCK signaling pathway, promote axon regeneration and improve the electrophysiological function and locomotor function of rats. Figures and Tables | References | Related Articles | Metrics

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Bone marrow mesenchymal stem cells-derived exosomes combined with chondroitinase ABC for treating spinal cord injury in rats Xie Xingqi, Hu Wei, Tu Guanjun 2022, 26 (1):  20-26.  doi: 10.12307/2022.004 Abstract ( 732 )   PDF (2369KB) ( 163 )   Save BACKGROUND: How to improve the local microenvironment, inhibit the formation of the glial scar, and promote repair and regeneration of damaged neurons and axons, are the difficulties of treating spinal cord injury. The research demonstrated that chondroitinase ABC can enhance the regeneration and plasticity of axons by degrading chondroitin sulfate proteoglycans. Meanwhile, bone marrow mesenchymal stem cells-derived exosome has a protective effect on spinal cord injury recovery by inhibiting apoptosis, regulating immune response, and regulating regeneration of damaged neurons. OBJECTIVE: To investigate the repair effect of bone marrow mesenchymal stem cells-derived exosome combined with chondroitinase ABC on spinal cord injury in rats and to explore its mechanism. METHODS:  Using the exosomes-extracted kit to isolate bone marrow mesenchymal stem cells-derived exosome, its morphology was observed under a transmission electron microscope. The expression levels of CD63 and Alix were identified through western blot assay. Totally 50 SD rats were randomly divided into five groups: sham group, model group, chondroitinase ABC group, exosome group, and combination group, with 10 rats in each group. Rat models of spinal cord injury were established by referencing the modified Allen’s method. In the chondroitinase ABC group and combination group, a micro syringe was applied to directly inject chondroitinase ABC into the injured area. At 2 hours after surgery, the models of the exosome group and the combination group were injected with bone marrow mesenchymal stem cells-derived exosomes through the tail vein, once every 2 days, for a total of 3 injections. The hind limb motor function was scored at 1, 3, 7, 14, and 28 days after surgery. At 14 days, six rats were taken from each group to make paraffin slices after perfusion. The pathological changes were observed at the injury region by hematoxylin-eosin staining. The expression of glial fibrillary acidic protein was detected by immunofluorescence and the expression of growth-associated protein-43 was identified by immunohistochemistry.    RESULTS AND CONCLUSION: (1) The exosomes presented a circular or elliptical shape or “saucer-like” and its size was uneven. The positive expression of its marker proteins CD63 and Alix could be observed. (2) Compared with the model, chondroitinase ABC, and exosome groups, BBB score was higher; damaged area was smaller; expression of glial fibrillary acidic protein was lower; the expression of growth-associated protein-43 was up-regulated in the combination group (all P < 0.05). (3) The results demonstrate that bone marrow mesenchymal stem cells-derived exosome combined with chondroitinase ABC can inhibit the expression of glial fibrillary acidic protein in the injured area, up-regulate the expression of growth-associated protein-43, and reduce the formation of the glial scar, which improve local microenvironment and promote the repair and regeneration of neurons and axons after spinal cord injury in rats. Figures and Tables | References | Related Articles | Metrics

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Acellular nerve scaffold combined with bone marrow mesenchymal stem cells and platelet-rich gel for femoral nerve injury Zhang Xuelei, Luo Gan, Yu Shenghui, Gu Zuchao, Peng Xu, He Xueling, Liu Yan, Zhang Xiaomei 2022, 26 (1):  27-32.  doi: 10.12307/2022.005 Abstract ( 439 )   PDF (1979KB) ( 229 )   Save BACKGROUND: The use of allogeneic acellular nerve scaffold combined with bone marrow mesenchymal stem cells and platelet-rich gel to treat rabbit sciatic nerve injury is currently less reported and the mechanism is less clear. OBJECTIVE: To evaluate the effect of transplantation of acellular nerve scaffold combined with bone marrow mesenchymal stem cells and platelet-rich gel in the rabbit sciatic nerve injury model. METHODS:  Twenty-five New Zealand rabbits were randomly divided into five groups: stump anastomosis group, acellular nerve scaffold group, acellular nerve scaffold combined with platelet-rich gel group, acellular nerve scaffold combined with bone marrow mesenchymal stem cell group, acellular nerve scaffold combined with platelet-rich plasma gel and bone marrow mesenchymal stem cell group. At 12 weeks after operation, the wet weight of gastrocnemius and histopathological staining experiments were performed.   RESULTS AND CONCLUSION: The wet weight of gastrocnemius in the acellular nerve scaffold combined with platelet-rich gel and bone marrow mesenchymal stem cell group was significantly higher than that in the other groups (P < 0.05); moreover, there were many regenerated nerve fibers, no inflammatory cell infiltration, and positive expression of neurofilament protein NF-200. It is indicated that the combination of acellular nerve scaffold and bone marrow mesenchymal stem cells and platelet-rich gel has a good effect on the regeneration of peripheral nerve injury.  Figures and Tables | References | Related Articles | Metrics

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Extracellular matrix of Schwann-like cells induced by bone marrow mesenchymal stem cells promotes axonal regeneration after peripheral nerve injury Zhao Laihe, Xia Bing, Ma Teng, Gao Jianbo, Li Shengyou, Gao Xue, Zheng Yi, Hu Guangwen, Luo Zhuojing, Huang Jinghui 2022, 26 (1):  33-39.  doi: 10.12307/2022.006 Abstract ( 545 )   PDF (2042KB) ( 212 )   Save BACKGROUND: Previous studies have found that Schwann cells and bone marrow mesenchymal stem cells-derived Schwann cells can promote axonal regeneration and functional recovery after peripheral nerve injury. However, the shortage of Schwann cells limited its application. Schwann-like cells-derived extracellular matrix is rarely reported in the treatment of peripheral nerve injury.  OBJECTIVE: To investigate whether Schwann-like cells-derived extracellular matrix contributes to nerve repair after peripheral nerve injury.  METHODS: Schwann cells and bone marrow mesenchymal stem cells were extracted from SD rats and the latter were induced into Schwann-like cells, then both were identified to prepare extracellular matrix. In vitro, dorsal root ganglion neurons and dorsal root ganglion tissue blocks were seeded on extracellular matrix to observe the growth of dorsal root ganglion axons. The sciatic nerve defect models of SD rats were established. The sciatic nerve axon regeneration and gastrocnemius muscle recovery were observed by using autologous nerve, Schwann-like cells-derived extracellular matrix composite poly(ε-caprolactone) conduit (induction group) and Schwann cells-derived extracellular matrix composite poly(ε-caprolactone) conduit (Schwann group) respectively.  RESULTS AND CONCLUSION: (1) The expression of p75NTR in Schwann-like cells was significantly higher than that in bone marrow mesenchymal stem cells (P < 0.05). The purity of Schwann cells was (95.20±4.63)%. (2) Schwann-like cells-derived extracellular matrix and Schwann cells-derived extracellular matrix could promote the growth of nerve axons in dorsal root ganglion tissue block in vitro. (3) In vivo experiment, regenerated nerve fibers in autologous nerve group were continuous and orderly arranged; regenerated nerve fibers in induction group and Schwann group penetrated through the defect area, similar to that in the autologous nerve group. (4) The results showed that Schwann-like cells-derived extracellular matrix and Schwann cells-derived extracellular matrix could promote axon regeneration and repair after peripheral nerve injury, which provided a new and convenient cell-free therapy for peripheral nerve injury.  Figures and Tables | References | Related Articles | Metrics

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Expression of aldehyde dehydrogenase 3B1 during human bone marrow mesenchymal stem cells senescence Mai Liping, He Guodong, Chen Shaoxian, Zhu Jiening, Hou Xinghua, Zhang Mengzhen, Li Xiaohong 2022, 26 (1):  40-44.  doi: 10.12307/2022.007 Abstract ( 497 )   PDF (1802KB) ( 157 )   Save BACKGROUND: Human bone marrow mesenchymal stem cells have the phenomenon of cell aging during passage in vitro, but the mechanism by which it occurs is not yet clear. Aldehyde dehydrogenase 3B1 has antioxidant effect. Oxidative stress is one of the important factors leading to cell senescence. Whether the expression level of aldehyde dehydrogenase 3B1 is related to human bone marrow mesenchymal stem cells senescence is still unclear. OBJECTIVE: To observe the expression of aldehyde dehydrogenase 3B1 in cellular senescence, providing a new research direction for aging mechanism of stem cells.   METHODS: The natural senescent model of human bone marrow mesenchymal stem cells was established and identified. The mRNA expression of aldehyde dehydrogenase 3B1 in human bone marrow mesenchymal stem cells was detected by bisulfite methylation sequencing and real-time qPCR. The protein level of aldehyde dehydrogenase 3B1 was detected by immunofluorescence and western blot assay.   RESULTS AND CONCLUSION: (1) Human bone marrow mesenchymal stem cells were cultured in subculture. β-Galactosidase staining showed that positive cells increased continuously, and the positive cells were the most obvious at passage 7 to 13. (2) Methylation sequencing showed that in passage 16 human bone marrow mesenchymal stem cells, the methylation level of aldehyde dehydrogenase 3B1 was down regulated. (3) The mRNA and protein levels of aldehyde dehydrogenase 3B1 were down regulated during the passage of human bone marrow mesenchymal stem cells in vitro. (4) The results show that aldehyde dehydrogenase 3B1 is down regulated in the natural senescence of human bone marrow mesenchymal stem cells, but its mechanism needs further study. Figures and Tables | References | Related Articles | Metrics

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Chondrogenic differentiation of peripheral blood-derived mesenchymal stem cells induced by transforming growth factor beta 3: a dose-effect relationship Yang Tengyun, Li Yanlin, Liu Dejian, Wang Guoliang, Zheng Zhujun 2022, 26 (1):  45-51.  doi: 10.12307/2022.008 Abstract ( 507 )   PDF (2569KB) ( 191 )   Save BACKGROUND: With the development of cartilage tissue engineering technology, there have been in vitro culture and animal experiments on repairing cartilage defects with peripheral blood-derived mesenchymal stem cells, and good progress has been made. Transforming growth factor beta 3 is often used in cell culture in vitro to induce chondrogenic differentiation of mesenchymal stem cells. However, in the experimental application, the dose-effect study of transforming growth factor beta 3 is rarely involved, and the cell culture experiments involving dose-effect often misuse one-way analysis of variance or t-test to analyze this kind of data.  OBJECTIVE: To analyze the dose-effect relationship of chondrogenic differentiation potency of peripheral blood-derived mesenchymal stem cells induced by transforming growth factor beta 3 by repeated measurement, in order to obtain a better dosage of transforming growth factor beta 3, and obtain a better effect of chondrogenic differentiation of peripheral blood-derived mesenchymal stem cells.   METHODS: After mobilization, extraction and culture of peripheral blood-derived mesenchymal stem cells of Diannan small eared pigs, transforming growth factor beta 3 at different concentrations (25-500 μg/L) was added for chondrogenic differentiation or not added (control group). Cell proliferation in each group was detected by CCK8 assay at 2, 4, 6, 8, 10, 12 and 14 days. At 3, 7, 14 and 21 days of culture, the supernatant of each group was collected, and the level of type II collagen in the supernatant was detected by ELISA. At 21 day of culture, toluidine blue staining was used to observe the expression of the aggregated proteoglycan. At 21 days, immunocytochemical staining was performed to observe the expression of type II collagen.     RESULTS AND CONCLUSION:  In the range of 25-500 μg/L, the proliferation ability of peripheral blood-derived mesenchymal stem cells was the strongest at the concentration of transforming growth factor beta 3 at 40 μg/L. The concentration of transforming growth factor beta 3 was more likely to promote the chondrogenic differentiation of peripheral blood-derived mesenchymal stem cells in 40 and 80 μg/L.   Figures and Tables | References | Related Articles | Metrics

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Effects of LINC02532 targeting miR-145 on proliferation, migration, invasion and apoptosis of pancreatic cancer stem cells Meng Defeng, Li Changzai, Wu Chuntao 2022, 26 (1):  52-58.  doi: 10.12307/2022.009 Abstract ( 494 )   PDF (2401KB) ( 150 )   Save BACKGROUND: Long non coding RNA (lncRNA) and microRNA (miRNA) are two types of small non-coding RNA that are involved in regulating cell proliferation, apoptosis and migration and other life activities, and lncRNA can also be used as a competitive endogenous RNA and miRNA target binding to regulate the expression of miRNA target genes and play an important role in the occurrence and development of tumors. LINC02532 is an lncRNA that can target miR-129-5p and miR-490-5p to promote the proliferation, migration and invasion of gastric cancer cells, but its effect on the biological behavior of pancreatic cancer stem cells and the action mechanism are still unknown.  OBJECTIVE: To investigate the effect and action mechanism of LINC02532 on the proliferation, migration, invasion and apoptosis of pancreatic cancer stem cells.  METHODS:  (1) Fifty-six patients with pancreatic cancer confirmed by pathological examination in North China University of Science and Technology Affiliated Hospital from January 2017 to June 2018 were selected as the research subjects. Real time fluorescent quantitative PCR was used to detect the expression levels of LINC02532 and miR-145 in pancreatic cancer tissues and adjacent tissues. (2) Using CD24+CD44+ESA+ as surface markers, pancreatic cancer stem cells were sorted from human pancreatic cancer cells PANC-1 by flow cytometry. Pancreatic cancer stem cells were divided into normal group, si-LINC02532 group (transfected with LINC02532 small interfering RNA), si-NC group (transfected with disorderly negative sequence), si-LINC02532+anti-miR-145 group (co-transfected with LINC02532 small interfering RNA and miR-145 inhibitor) and si-LINC02532+anti-miR-NC group (co-transfected with LINC02532 small interfering RNA and miR-145 inhibitor negative control sequence). At 12 hours after transfection, real time fluorescent quantitative PCR was used to detect the expression levels of LINC02532 and miR-145 in each group of cells. Cell counting kit-8 (CCK-8) assay was utilized to detect the cell survival rate. The colony formation test was applied to detect the number of cell clones formed. Transwell chamber was used to detect cell migration and invasion. Flow cytometry was utilized to detect cell apoptosis rate. Western blot assay was used to detect the expression levels of P21, Bax, Caspase-3, E-cadherin and MMP-2 protein. The double luciferase reporter gene experiment was utilized to verify the regulatory relationship between miR-145 and LINC02532.    RESULTS AND CONCLUSION: (1) Compared with adjacent tissues, the expression level of LINC02532 increased in pancreatic cancer tissues (P < 0.05), while the expression level of miR-145 decreased (P < 0.05). (2) Compared with the si-NC group, the survival rate, colony formation, cell migration and invasion number, and MMP-2 protein expression level of pancreatic cancer stem cells reduced in the si-LINC02532 group (P < 0.05), while the apoptotic rate and the expression levels of P21 and Bax, Caspase-3 and E-cadherin protein increased (P < 0.05), but there was no significant difference between the si-NC group and the normal group (P > 0.05). (3) LINC02532 targeted negatively regulated miR-145 expression in pancreatic cancer stem cells. Compared with the si-LINC02532+anti-miR-NC group, the survival rate, colony formation, cell migration and invasion number, and MMP-2 protein expression level of pancreatic cancer stem cells increased in the si-LINC02532+anti-miR-145 group (P < 0.05), while the apoptotic rate and the expression levels of P21 and Bax, Caspase-3 and E-cadherin protein reduced (P < 0.05). (4) The results show that LINC02532 was up-regulated in pancreatic cancer tissues, and down-regulating its expression may inhibit the proliferation, migration and invasion of pancreatic cancer stem cells by targeting up-regulation of miR-145 expression, and induce apoptosis. Figures and Tables | References | Related Articles | Metrics

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miR-210/YWHAG axis with adipocyte proliferation and angiogenesis after autologous fat transplantation Yao Yanyi, Chen Xiaoling, Zhang Min, Wang Hong, Hao Liying, Shi Chao, Zhao Bingfeng, Jin Yaqiao, Dong Wei 2022, 26 (1):  59-63.  doi: 10.12307/2022.010 Abstract ( 591 )   PDF (1843KB) ( 270 )   Save BACKGROUND: Autologous adipose tissue had been became an excellent filling material because of its advantages of no immune rejection, convenient material extraction, and convenient operation. The study found that the transplanted adipocyte had been in the environment of ischemia and hypoxia before the reconstruction of the vascular network, and such an environment was easy to induce apoptosis and necrosis of adipocytes. How to accelerate the process of proliferation and angiogenesis and inhibit the apoptosis of fat cells is the focus of research on improving the survival rate of autologous fat transplantation. OBJECTIVE: To explore the mechanism of the effect of miR-210 on the survival of autologous fat transplantation via YWHAG. METHODS:  After 8 weeks of autologous adipose tissue transplantation in Sprague-Dawley rats, the adipose tissue on the back was stripped. The expression levels of miRNAs in adipose tissue were detected by RT-qPCR. The targeting relationship between miR-210 and YWHAG was validated by dual luciferase reporter gene. Adipocytes were isolated from the fat tissues and divided into miR-210 inhibition group, YWHAG overexpression group, miR-210 and YWHAG overexpression group for cell transfection. The expression levels of vascular endothelial growth factor, Endostatin and YWHAG were detected by western blotting. The effects of the miR-210/YWHAG axis on proliferation, apoptosis and angiogenesis of adipocytes were detected by CCK-8, Annexin V-FITC/PI and angiogenesis assay, respectively.   RESULTS AND CONCLUSION: (1) miR-210 was highly expressed in adipose tissue (P < 0.001). (2) The results of dual luciferase reporter gene indicated that YWHAG was targeting protein of miR-210 (P < 0.05). (3) Knockdown of miR-210 significantly inhibited proliferation, angiogenesis and induced apoptosis of adipocytes (P < 0.05). (4) Overexpression of miR-210 and YWHAG at the same time had no significant effect on adipocyte proliferation, apoptosis and angiogenesis. (5) In summary, miR-210 promoted autologous fat graft survival by downregulating the expression level of YWHAG to promote proliferation, angiogenesis and inhibiting apoptosis of adipocytes. Figures and Tables | References | Related Articles | Metrics

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Icariin promotes differentiation of mouse preosteoblasts via activating autophagy Yang Bingxuan, Jiang Tao, Jia Min, Li Peng, Liao Rongzhen, Li Zhao, Shao Min 2022, 26 (1):  64-69.  doi: 10.12307/2022.011 Abstract ( 566 )   PDF (1620KB) ( 116 )   Save BACKGROUND: Studies have found that icariin can promote the proliferation and differentiation of mouse preosteoblasts. Nuclear factor-κB signaling pathways and autophagy play an important role in the regulation of osteoblast differentiation. Whether they are involved in icariin promoting the proliferation and differentiation of mouse preosteoblasts remains unclear. OBJECTIVE: To investigate the effect of icariin on the proliferation and differentiation of mouse preosteoblasts and the role of nuclear factor-κB signaling and autophagy.  METHODS: (1) Screening out the best intervention concentration of icariin: Mouse preosteoblasts MC3T3-E1 cells were divided into control group and various icariin groups (0.01, 0.1, 1, 10, 100 μmol/L). MTS was used to detect the proliferation activity of mouse preosteoblasts from different groups after icariin intervention. Osteogenic differentiation was assessed by Alizarin red staining. The osteoblastic differentiation ability and autophagy activity in mouse preosteoblasts from different groups were evaluated by western blot assay after icariin intervention. (2) 3-Methyladenine was added to inhibit autophagy. Four groups were set up: control group, 3-methyladenine group, icariin group, and 3-methyladenine + icariin group. Alizarin red staining was used to observe the mineralized nodules. Western blot assay was utilized to determine the expression levels of alkaline phosphatase, Runx2, p62, LC3, NF-κB p65 and p-NF-κB p65 protein.   RESULTS AND CONCLUSION: (1) Icariin could promote the proliferation of mouse preosteoblasts and the effect was the most obvious at 10 μmol/L (P < 0.05). The formation of mineralized nodules in the 10 μmol/L icariin group was significantly more than that in the control group and the expression levels of alkaline phosphatase and Runx2 protein were significantly increased (P < 0.05). Compared with the control group, the expression levels of Beclin1, LC3 II/LC3 I increased significantly and the expression of p62 decreased in the 10 μmol/L icariin group (P < 0.05). (2) After 3-methyladenine inhibited autophagy, compared with the icariin group, the expression of alkaline phosphatase, Runx2, LC3 II/LC3 I decreased and the expression of p62 increased in the 3-methyladenine + icariin group (P < 0.05). (3) Compared with the control group, the expression of p-p65/p65 decreased in the 10 μmol/L icariin group (P < 0.05). (4) These results indicate that icariin may promote osteogenic differentiation of MC3T3-E1 cells by down-regulation of the nuclear factor-κB signaling and enhancing autophagy.  Figures and Tables | References | Related Articles | Metrics

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Mechanism by which miR-146a regulates osteogenic differentiation of adipose derived mesenchymal stem cells Huang Tao, Cheng Zhijian, Jia Zhiqiang, Zhao Xiaoguang, Wang Lei, Zhai Wenjing, Zhou Yongxin 2022, 26 (1):  70-75.  doi: 10.12307/2022.012 Abstract ( 462 )   PDF (1671KB) ( 245 )   Save BACKGROUND: Previous studies have shown that miR-146a can affect the osteogenic differentiation of bone marrow mesenchymal stem cells, but its regulatory function in adipose derived mesenchymal stem cells has not been elucidated. OBJECTIVE: To investigate the regulatory role of miR-146a in the osteogenic differentiation of mouse adipose derived mesenchymal stem cells. METHODS:  Adipose derived mesenchymal stem cells were obtained from male C57BL/6 mice. The cell morphology was observed by inverted microscope, and the expression of CD29, CD44 and CD45 of passage 3 cells was detected by flow cytometry. miR-NC, miR-146a mimics and miR-146a inhibitor were transfected into adipose derived mesenchymal stem cells for osteogenic differentiation. On day 6 of osteogenic induction, alkaline phosphatase staining was used to observe the degree of calcification. RT-PCR and western blot assay were used to detect the expression of osteogenic phenotype markers. On day 12 of osteogenic induction, alizarin red staining was used to identify the formation of mineralized matrix on the cell surface.   RESULTS AND CONCLUSION: (1) The cultured cells were spindle shaped and fibroblast like. The expression of CD29 and CD44 was high and that of CD45 was low. (2) The expression of miR-146a in mouse adipose derived mesenchymal stem cells decreased with the prolongation of osteogenic induction time (P < 0.05). (3) Compared with miR-NC group, the amount and activity of alkaline phosphatase precipitates in miR-146a mimic group were significantly lower than those in miR-146a inhibitor group (P < 0.05). (4) Compared with miR-NC group, the mRNA and protein expressions of ALP, Runx2, Akt, p-Akt, PI3K and p-PI3K were significantly decreased in miR-146a mimic group, but significantly increased in miR-146a inhibitor group (P < 0.05). (5) Compared with miR-NC group, alizarin red staining showed that the degree of calcification in miR-146a mimic group was significantly lower (P < 0.05), while that in miR-146a inhibitor group was significantly higher (P < 0.05). (6) These results suggest that miR-146a can negatively regulate the differentiation of adipose derived mesenchymal stem cells into osteoblasts through PI3K/AKT signaling pathway. Figures and Tables | References | Related Articles | Metrics

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Expression and regulation of keratin 6B in CD44+ bladder cancer stem cells Liu Lu, Yang Yuming, Shang Aichen, Liu Cui, Sun Ce, Wang Jing 2022, 26 (1):  76-83.  doi: 10.12307/2022.013 Abstract ( 561 )   PDF (2166KB) ( 138 )   Save BACKGROUND: Bladder cancer stem cells could promote the recurrence and drug resistance of bladder cancer. Numerous studies have shown that keratin 6B (KRT6B) is involved in the production and progression of tumors, and is closely related to the prognosis of tumors.  OBJECTIVE: To observe the expression of keratin 6B in CD44+ bladder cancer stem cells and to show the influence of keratin 6B on proliferation, migration, and self-renewal of bladder cancer stem cells, and to further explore the effect of keratin 6B expression on the prognosis of bladder cancer patients.  METHODS: (1) CD44+ 5637 bladder cancer stem cells were isolated by magnetic active cell sorting. Cancer stem cell-related gene expression of SOX2, OCT4, and NANOG was detected via real-time polymerase chain reaction. The spheroid formation assay was used to detect the ability of self-renewal of cancer stem cells in CD44+ cells. Keratin 6B expression was detected in CD44+ bladder cancer stem cells by real-time polymerase chain reaction. (2) The CD44+ 5637 bladder cancer stem cells were divided into two groups. In the keratin 6B siRNA group, keratin 6B small interfering RNA was transfected into CD44+ bladder cancer stem cells. Untransfected CD44+ bladder cancer stem cells were used as the black control group. Cells were collected at 2 days post-transfection. The proliferation, migration, and self-renewal capacity of keratin 6B siRNA CD44+ bladder cancer stem cells were detected by the colony and wound healing assay and spheroid formation respectively. (3) Totally 24 bladder cancer tissues were used by immunohistochemistry to analyze the expression of CD44v6 and keratin 6B. (4) ONCOMINE database was used to analyze the effect of keratin 6B expression on the overall survival of bladder cancer. RESULTS AND CONCLUSION: (1) Cancer stem cell-related genes (SOX2, OCT4, NANOG) and keratin 6B expression was higher in CD44+ cells isolated by magnetic active cell sorting compared with CD44- cells (P < 0.05). Cell proliferation, migration, and in vitro spheroid formation were significantly increased (P < 0.05). Keratin 6B small interfering RNA down-regulated the expression of keratin 6B in CD44+ bladder cancer stem cells (P < 0.05). (2) Compared with the blank control group, the proliferation and migration of CD44+ bladder cancer stem cells after transfection of keratin 6B small interfering RNA (P < 0.05), and the number of tumorsphere significantly diminished (P < 0.05); the expression of Notch1 and Hes1 mRNA increased (P < 0.05). (3) Keratin 6B and CD44v6 were significantly different in bladder cancer tissue (P=0.006). The overall survival rate of bladder cancer patients with high expression of keratin 6B was lower than that of patients with low expression of keratin 6B. (4) The results showed that keratin 6B was highly expressed in CD44+ bladder cancer stem cells, and could promote the proliferation, migration, and self-renewal capacity of bladder cancer stem cells. The high expression of keratin 6B contributes to improving the survival of bladder cancer patients. Figures and Tables | References | Related Articles | Metrics

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Expression and significance of DNA topoisomerase II in neural stem cells of ICR mice Sun Mengjun, Guo Jianmei, Zhou Gengsu, Dong Zefei, Zheng Chungui, Cao Cuili 2022, 26 (1):  84-89.  doi: 10.12307/2022.014 Abstract ( 548 )   PDF (1501KB) ( 147 )   Save BACKGROUND:  Embryonic neural stem cells can differentiate into neurons and glial cells. In practical applications, we hope that neural stem cells will differentiate into neurons more. Therefore, it is very important to study the mechanism of directional differentiation of neural stem cells into neurons. DNA topoisomerase II is a type of nucleoprotein widely present in organisms and plays an important role in life activities such as DNA replication, repair, transcription, recombination and chromosome separation.  OBJECTIVE: To explore the expression and significance of DNA topoisomerase II in neural stem cells and their directional differentiation into neurons. METHODS:  Neural stem cells were isolated from cerebral cortex of ICR mice (E12.5 d) and cultured. The single cells after digestion were inoculated in a petri dish at 5×108 L-1 after matting with Matrigel. The conditioned medium of neurogenic differentiation containing B27, N2 and 10 μg/L glial cell line derived neurotrophic factor was added. At 1, 2, and 3 days after culture, the expression of DNA topoisomerase II α and β was detected by immunocytochemistry, western blot assay, and real time-quantitative PCR.  RESULTS AND CONCLUSION: (1) The number of DNA topoisomerase IIα-positive cells in neurospheres was large and evenly distributed, and the number of positive cells after induced differentiation was reduced. The number of DNA topoisomerase IIβ-positive cells in neurospheres was relatively small, mainly distributed in the center of neurospheres. After induced differentiation, the number of positive cells began to increase gradually. At 2 days, the expression reached a peak, and then showed a decreasing trend. (2) The expression of DNA topoisomerase IIα protein and mRNA in neurospheres was high and gradually decreased after the differentiation into neurons. The expression of DNA topoisomerase IIβ protein and mRNA in neurospheres was low and significantly increased after neuronal differentiation. (3) Through experiments, it is concluded that DNA topoisomerase IIβ participates in the directional differentiation of neural stem cells into neurons. Figures and Tables | References | Related Articles | Metrics

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Repair of calvarial defects in osteoporotic mice by adipose-derived stem cells combined with biphasic calcium phosphate ceramic scaffold Jing Jin, Zhao Shandi, Chen Long, Peng Shuanglin, Tang Hui, Guo Daijin, Zeng Xinyi, Xiao Jingang 2022, 26 (1):  90-95.  doi: 10.12307/2022.015 Abstract ( 690 )   PDF (2335KB) ( 334 )   Save BACKGROUND: Researches have shown that biphasic calcium phosphate can be used as an effective bone substitute for the repair of critical-size defects in animal models with osteoporosis, and osteoporosis adipose-derived stem cells (OP-ASCs) is promising for medical applications in patients with osteoporotic fractures and its secondary bone defects. The previous research results of the research group showed that compared with normal adipose-derived stem cells, the in vitro proliferation and osteogenic differentiation potential of OP-ASCs from osteoporosis mice were obviously reduced.  OBJECTIVE: To investigate the effect of OP-ASCs combined with biphasic calcium phosphate on the repair of calvarial critical-size defects in osteoporotic mice.  METHODS: Eighteen C57BL/6 female mice were divided into three groups randomly: blank group, biphasic calcium phosphate group, and OP-ASCs/biphasic calcium phosphate group. The models of osteoporosis with calvarial critical-size defects were established in each group, and then the blank group was not implanted with materials. The biphasic calcium phosphate and OP-ASCs/biphasic calcium phosphate groups were implanted with biphasic calcium phosphate ceramic scaffolds only, and OP-ASCs/biphasic calcium phosphate admixtures separately. The mice were sacrificed at the 8 (n=3) and 12 (n=3) weeks. The differences in bone formation at the calvarial defects were detected by micro-CT, hematoxylin-eosin staining, and Masson Trichrome staining.    RESULTS AND CONCLUSION: (1) There was a small amount of bone formation in the blank group both at 8 and 12 weeks after implantation, and the new bone tissue grown well in both the biphasic calcium phosphate group and the OP-ASCs/biphasic calcium phosphate group; the OP-ASCs/biphasic calcium phosphate group achieved more bone formation than that of the biphasic calcium phosphate group (P < 0.05). (2) Compared with that at 8 weeks, both the biphasic calcium phosphate group and the OP-ASCs/biphasic calcium phosphate group showed more bone formation at 12 weeks (P < 0.05), and the difference of bone formation between the OP-ASCs/biphasic calcium phosphate group and the biphasic calcium phosphate group was more obvious than that at 8 weeks (P < 0.05). (3) To conclude, OP-ASCs combined with biphasic calcium phosphate could repair the calvarial critical-size defects in osteoporosis mice effectively to some extent, and the effect is better than that of the biphasic calcium phosphate used alone.  Figures and Tables | References | Related Articles | Metrics

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High glucose induces high expression of stem cell factor in human renal tubular epithelial cells Xu Xueling, Liu Jun, Yang Aihua, Wang Huifang, Guo Dandan, Liu Xuemei, Xu Yan 2022, 26 (1):  96-100.  doi: 10.12307/2022.016 Abstract ( 559 )   PDF (1498KB) ( 90 )   Save BACKGROUND: Diabetic kidney disease is one of the most serious and common chronic complications of diabetes. It has become an important cause of end-stage renal failure. However, the exact mechanism of its occurrence and development is still unclear, and precise and effective prevention and treatment measures are lacking. OBJECTIVE: To investigate the effect of hypertonic glucose on the phenotype changes of human renal tubular epithelial cells and the expression of stem cell factor. METHODS:  Human renal tubular epithelial cells were cultured in vitro and divided into normal glucose group, high glucose stimulation group, and mannitol control group. The cells of each group were separately collected at 0, 12, 24 and 48 hours for detection. The cell morphology was observed under an inverted microscope. Real-time quantitative PCR and western blot assay were used to detect the expression of mRNA and protein of stem cell factor, α-smooth muscle actin, type I collagen, and fibronectin.    RESULTS AND CONCLUSION: (1) Compared with the normal glucose group, the renal tubular epithelial cell morphology of the high glucose stimulation group changed significantly, but the cell morphology of the mannitol control group did not change significantly compared with renal tubular epithelial cells that grow normally. (2) The expression levels of mRNAs and proteins of stem cell factor, α-smooth muscle actin, type I collagen, and fibronectin of renal tubular epithelial cells in high glucose stimulation group were significantly higher than those of the normal glucose group, and increased in a time-dependent manner. (3) The expression levels of stem cell factor mRNA and protein in renal tubular epithelial cells were positively correlated with α-smooth muscle actin, type I collagen, and fibronectin. (4) These findings indicate that hypertonic glucose can up-regulate the expression of stem cell factor in renal tubular epithelial cells in a time-dependent way, meanwhile up-regulating the expression of α-smooth muscle actin, type I collagen and fibronectin, indicating that hypertonic glucose stimulates the transdifferentiation of renal tubular epithelial cells and the production of a large number of extracellular matrix, which promotes renal interstitial fibrosis.   Figures and Tables | References | Related Articles | Metrics

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Effects of miRNA in self-renewal, multidirectional differentiation, fate and function regulation of bone marrow mesenchymal stem cells  Cui Shuaishuai, Yang Xiaohong 2022, 26 (1):  101-105.  doi: 10.12307/2022.017 Abstract ( 476 )   PDF (1066KB) ( 186 )   Save BACKGROUND: Studies have confirmed that miRNAs are involved in self-renewal, multidirectional differentiation, fate determination, functional exercise and other aspects of bone marrow mesenchymal stem cells, and have become a hot spot in the medical field.  OBJECTIVE: To review regulatory effect of miRNAs on bone marrow mesenchymal stem cells and its possible molecular mechanism.  METHODS: PubMed was retrieved with the key words of “BMSCs, miRNA, proliferation, osteogenic differentiation, adipogenic differentiation, chondrogenic differentiation” in English. The retrieval time was from 2011 to 2021. After initial screening of titles and abstracts, irrelevant articles were excluded, and 51 eligible articles were included for result analysis.  RESULTS AND CONCLUSION: miRNA plays an important role by targeting major genes and signaling pathways related to osteogenic differentiation, adipogenic differentiation, and chondrogenic differentiation. A large number of miRNAs have been shown to be associated with bone metabolic diseases such as osteoporosis and osteoarthritis, which seriously affect the quality of life of patients and impose a heavy burden on society. Therefore, more in-depth research and exploration on miRNAs and a better understanding of the regulation of the expression of these miRNAs will contribute to the development of targeted therapies for bone metabolism related diseases. Figures and Tables | References | Related Articles | Metrics

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Biological function of circular RNAs in osteogenic differentiation of mesenchymal stem cells Kang Yue, Liu Jie 2022, 26 (1):  106-111.  doi: 10.12307/2022.018 Abstract ( 808 )   PDF (1078KB) ( 211 )   Save BACKGROUND: Circular RNAs (circRNAs) were initially regarded as by-products of aberrant splicing. Present research on their mechanism has gradually penetrated to the molecular level. Many studies have shown that circRNAs participate in osteogenic differentiation through various ways and play a key role. OBJECTIVE: To discuss the research progress of circRNAs during osteogenic differentiation in human mesenchymal stem cells. METHODS: Using “circRNAs, human mesenchymal stem cells, osteogenic differentiation” as keywords in English and Chinese. PubMed, Web of Science, CNKI, and Wanfang were searched for relevant articles on circRNAs in human mesenchymal stem cells published from 1993 to 2020. Types of retrieved articles included reviews, research papers, and books.  RESULTS AND CONCLUSION: CircRNAs play an important role in the osteogenesis of mesenchymal stem cells. These circRNAs have proven to be key targets for the diagnosis and treatment of bone diseases. However, the molecular mechanism of circRNA in osteogenic differentiation needs further research, and in vivo experiments are also needed to support existing conclusions. Figures and Tables | References | Related Articles | Metrics

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Regulation of proliferation, differentiation and apoptosis of bone-related cells by long-stranded non-coding RNA Feng Zhiguo, Sun Haibiao, Han Xiaoqiang 2022, 26 (1):  112-118.  doi: 10.12307/2022.019 Abstract ( 626 )   PDF (1225KB) ( 235 )   Save BACKGROUND: Long-stranded non-coding RNA is an important epigenetic regulator that controls gene expression and affects a variety of biological processes. More and more evidence shows that long-stranded non-coding RNA plays a potential role in regulating the proliferation, differentiation and apoptosis of bone marrow mesenchymal stem cells, osteoblasts, osteoclasts and chondrocytes. OBJECTIVE: To review the latest research progress on the effects of long-stranded non-coding RNA on the function of bone marrow mesenchymal stem cells, osteoblasts, osteoclasts and chondrocytes, the regulatory mechanism of long-stranded non-coding RNA and the signal pathway involved, in order to provide a new theoretical basis for the treatment of osteoporosis and osteoarthritis. METHODS: PubMed, Biosos Preview and Web Of Science were used to search the related articles published from database inception to August 2020. The retrieval key words were “long non-coding RNA, bone marrow mesenchymal stem cells, osteoblasts, osteoclasts, chondrocytes, differentiation, signal pathway”. Finally, 68 articles related to this article were selected according to inclusion criteria and after screening contents, abstracts, and titles.     RESULTS AND CONCLUSION: (1) Long-stranded non-coding RNA is a key regulatory molecule with multiple biological functions. Long-stranded non-coding RNA regulates different signal pathways through various mechanisms, and further regulates the proliferation, differentiation and apoptosis of medullary mesenchymal stem cells, osteoblasts, osteoclasts and chondrocytes, and inhibit or promote the process of osteoporosis and osteoarthritis. (2) Common Long-stranded non-coding RNA regulatory signal pathways include WNT, TGF-β/BMPs, NOTCH and PI3K/AKT. These signaling pathways often have crosstalk, and are jointly involved in the regulation of bone cell metabolism. Coding RNA and non-coding RNA regulate each other by competing for miRNA binding sites.  Figures and Tables | References | Related Articles | Metrics

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Effect and mechanism of the effective components of Chinese medicine on promoting the differentiation of bone marrow mesenchymal stem cells into chondrocytes Liu Xiaogang, Li Tian, Zhang Duo 2022, 26 (1):  119-124.  doi: 10.12307/2022.020 Abstract ( 603 )   PDF (1201KB) ( 363 )   Save BACKGROUND: Bone marrow mesenchymal stem cells are one of the most popular seed cells in cartilage tissue engineering. With the continuous advancement of medical research, many experiments have shown that certain active ingredients of traditional Chinese medicine can promote the induction of bone marrow mesenchymal stem cells into chondrocytes. OBJECTIVE: To review the regulatory mechanism and existing problems of different types of compound Chinese medicines and single Chinese medicine and their application in promoting the differentiation of bone marrow mesenchymal stem cells into chondrocytes, in order to provide research ideas for the promoting effect of the effective ingredients of Chinese medicine on the differentiation of bone marrow mesenchymal stem cells into chondrocytes. METHODS: The first author searched the relevant articles in CNKI, Wanfang, PubMed, Scopus and Web of Science databases, and used “compound Chinese medicine; single Chinese medicine; bone marrow mesenchymal stem cell; chondrocytes; tissue engineering” as the Chinese and English search terms. Finally, 60 articles meeting the criteria were selected for review. RESULTS AND CONCLUSION: (1) The active ingredients of certain compound Chinese medicines and single Chinese medicine have a promoting effect on the induction of bone marrow mesenchymal stem cells into chondrocytes, which is an important part of the application of Chinese medicine in cartilage tissue engineering research. (2) Using the effective ingredients of traditional Chinese medicine to induce bone marrow mesenchymal stem cells to differentiate into chondrocytes, and gradually applying them to cartilage tissue engineering for cartilage repair, has become a hot trend in the continuous development and growth of Chinese medicine. Among them, Tougu Xiaotong Granules have good effects with ginsenosides, astragaloside IV, and ligustrazine, and more experimental projects can be launched for research. Figures and Tables | References | Related Articles | Metrics

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Research hotspots and application potential of stem cells from human exfoliated deciduous teeth Wei Shan, Li Qin, Su Yi 2022, 26 (1):  125-129.  doi: 10.12307/2022.021 Abstract ( 776 )   PDF (1032KB) ( 202 )   Save BACKGROUND: The stem cells from human exfoliated deciduous teeth have strong proliferation and differentiation potential and can be easily obtained, and then have gradually become a research hotspot in the field of stem cells.  OBJECTIVE: To review the general biological characteristics and clinical treatments of stem cells from human exfoliated deciduous teeth. METHODS: Wanfang, CNKI, VIP, Medline, and PubMed databases were searched, with the Chinese subject headings “stem cells from deciduous teeth, micro-environment, gene therapy” and English subject headings “human exfoliated deciduous teeth, dental pulp, stem cell, gene therapy”. A total of 239 articles were obtained by preliminary examination. The latest research articles in the last 5 years and the articles with impact factor over 5 in recent 10 years were selected. The articles were evaluated by all the authors, and 196 articles with repeated content and outdated content and poor correlation were excluded. Finally, 44 articles were included for review.  RESULTS AND CONCLUSION: Stem cells from human exfoliated deciduous teeth have a high proliferation rate and can differentiate into a variety of tissues. Stem cells from human exfoliated deciduous teeth are easy to get, and there is no immune rejection reaction. With the emergence of more and more stem cell banks, stem cells from human exfoliated deciduous teeth will provide broader application prospects for tissue engineering and medicine.  Figures and Tables | References | Related Articles | Metrics

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Effect of mesenchymal stem cells on myocardial ischemia-reperfusion injury Zhao Xu, Mao Xin, Li Chuntian, Wang Feng 2022, 26 (1):  130-134.  doi: 10.12307/2022.022 Abstract ( 594 )   PDF (1119KB) ( 208 )   Save BACKGROUND: Mesenchymal stem cells have the functions of inhibiting inflammation and cell apoptosis, promoting tissue repair, angiogenesis, and immune regulation in ischemic heart disease. OBJECTIVE: To review the latest research progress of mesenchymal stem cells in myocardial ischemia-reperfusion injury to provide ideas and basis for their further research and clinical application. METHODS: PubMed, Wanfang, and CNKI databases were searched for relevant literature. The key words were “mesenchymal stem cell, MSCs, myocardial ischemia-reperfusion injury, MIRI, exosomes, inflammation, tissue repair, vascular regeneration” in Chinese and English, separately. Finally, 48 articles were included and further summarized.   RESULTS AND CONCLUSION: Myocardial ischemia-reperfusion injury is a common pathophysiological process in clinical heart diseases. It is common in ischemic cardiomyopathy, cardiopulmonary bypass and heart transplantation. Its mechanisms include free radical damage, calcium ion overload, energy metabolism disorders, and inflammation and so on. In recent years, the treatment of mesenchymal stem cell transplantation has attracted attention. Its exosomal function, myocardial tissue repair, reduction of myocardial cell apoptosis and inhibition of inflammation provide a new idea for treatment of myocardial ischemia-reperfusion injury. Adult mesenchymal stem cells are currently the first choice for the treatment of myocardial ischemia-reperfusion injury. Therefore, a better understanding of the mechanism of mesenchymal stem cells in myocardial ischemia-reperfusion injury and the latest research progress are extremely important for their in-depth research and clinical application. Figures and Tables | References | Related Articles | Metrics

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Research status and problems of stem cells and their derived exosomes for prevention and treatment of vascular restenosis Shuai Zhiqin, Chen Jiameng, Liu Taotao, Hu Anling, Li Lisheng, Yu Limei, Xu Shangfu 2022, 26 (1):  135-140.  doi: 10.12307/2022.023 Abstract ( 482 )   PDF (1302KB) ( 342 )   Save BACKGROUND: Restenosis seriously affects the long-term effect of interventional therapy for coronary atherosclerotic heart disease. The multi-directional differentiation ability and secretion function of stem cells are closely related to the occurrence, development and outcome of restenosis. Stem cells provide new ideas for the prevention and treatment of vascular restenosis, and have great potential advantages. OBJECTIVE: To summarize the effect and mechanism of endothelial progenitor cells, mesenchymal stem cells and stem cell derived exosomes. METHODS: CNKI and PubMed databases were searched with the keywords of “stem cell”, “exosomes” and/or “restenosis” in English and Chinese, separately. Finally, 83 articles were included for review.  RESULTS AND CONCLUSION: (1) Restenosis seriously affects the long-term efficacy of coronary intervention, which is still an important issue to be solved in clinical practice. (2) Endothelial progenitor cell and mesenchymal stem cell transplantation can prevent and treat vascular restenosis. The mechanism mainly involves direct differentiation and repair of vascular endothelium and paracrine, and influences the microenvironment of injured vessels. (3) Stem cell derived exosomes can not only produce stem cell transplantation like effects, but also avoid the defects of stem cell transplantation, which has unique potential advantages in the prevention and treatment of vascular restenosis. Figures and Tables | References | Related Articles | Metrics

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Latest progress and mechanisms of mesenchymal stem cells on premature ovarian failure Li Zhongkang, Zheng Jiahua, Tian Yanpeng, Huang Xianghua 2022, 26 (1):  141-147.  doi: 10.12307/2022.024 Abstract ( 1286 )   PDF (1227KB) ( 407 )   Save BACKGROUND: Premature ovarian failure is a common gynecological endocrine disease, which seriously affects the patient’s physiological, fertility, and psychological functions. Unfortunately, curative therapies are not available at present, and current treatments are mainly address the symptoms. Mesenchymal stem cell transplantation is performed with excellent results and has been widely studied in premature ovarian failure. However, the mechanisms behind it are still undergoing intensive research. OBJECTIVE: To summarize and analyze the research progress of mesenchymal stem cells in the treatment of premature ovarian failure in recent years, to explore the related treatment mechanisms, and to evaluate its potential for clinical treatment so as to provide a theoretical basis for research and clinical application. METHODS: We searched the articles in CNKI and PubMed with the keywords of “mesenchymal stem cells, premature ovarian failure, premature ovarian insufficiency” in Chinese and English, respectively. Finally, 55 articles met the criteria for review. RESULTS AND CONCLUSION: All kinds of mesenchymal stem cells have a great therapeutic effect on premature ovarian failure cell and animal models. The therapeutic mechanisms include homing, promoting cell proliferation, inhibiting cell apoptosis, differentiation, immunoregulation, secreting a variety of cytokines, regulating autophagy and regulating ovarian microenvironment. In addition to a large number of basic researches, related clinical researches have also been carried out. However, its clinical application research is still in its infancy, and its safety and effectiveness still need to be verified by further clinical studies. Figures and Tables | References | Related Articles | Metrics

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Effect and mechanism of mesenchymal stem cells in the treatment of diabetic nephropathy Wang Shuyun, Xie Junhui, Yu Xuefeng 2022, 26 (1):  148-152.  doi: 10.12307/2022.025 Abstract ( 1014 )   PDF (1353KB) ( 218 )   Save BACKGROUND: Diabetic nephropathy has become one of the main causes of end-stage renal disease, but clinical treatment is still limited. In recent years, studies have found that mesenchymal stem cells exert renal protective effects in diabetic nephropathy. OBJECTIVE: To review the research advances of mesenchymal stem cells in diabetic nephropathy from three aspects: the pathogenesis and general treatment strategies of diabetic nephropathy, the characteristics and clinical application of mesenchymal stem cells, and the renal protective effect of mesenchymal stem cells on diabetic nephropathy. METHODS: Relevant research, reviews and treatises were searched in PubMed database and the search terms included “mesenchymal stem cells, MSCs, diabetic nephropathy, diabetic kidney disease”. Totally 62 articles were included for review based on inclusion and exclusion criteria. RESULTS AND CONCLUSION: The research of mesenchymal stem cells in disease treatment has been widely carried out. However, there are few clinical trials of mesenchymal stem cells in the treatment of diabetic nephropathy, and the clinical efficacy is limited. Animal experiments have confirmed that mesenchymal stem cells can play a protective role in kidney and delay the progression of diabetic nephropathy. The mechanisms include reducing renal cell apoptosis, regulating autophagy, ameliorating inflammation, suppressing oxidative stress, and inhibiting fibrosis.  Figures and Tables | References | Related Articles | Metrics

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Research hotspots and application value of tissue-engineered skin Lin Miaoyuan, Li Yuwan, Liu Yi, Chen Bei, Zhang Li 2022, 26 (1):  153-159.  doi: 10.12307/2022.026 Abstract ( 906 )   PDF (1229KB) ( 1137 )   Save BACKGROUND: Tissue-engineered skin has a good application prospect in promoting skin tissue wound repair and scarless healing.  OBJECTIVE: To review the current research progress, application and value of tissue-engineered skin in vivo and in vitro.  METHODS: A computer was used to search the relevant articles in the CNKI database and PubMed database. The Chinese and English search terms were “mesenchymal stem cells; growth factors; skin; wounds; skin repair; wound healing; regenerative medicine; tissue engineering; scaffolds”. The domestic and foreign related application articles on tissue-engineered skin construction in the treatment of skin tissue injury in recent years were checked, and the research progress of mesenchymal stem cells, growth factors, scaffold materials and dressings for new treatment methods for tissue repair was also summarized. The articles irrelevant to the subject of this article were excluded, and 78 articles were finally included for the result analysis.  RESULTS AND CONCLUSION: The construction of tissue-engineered skin involves the selection of seed cells, the application of growth factors, and the combination of multiple elements of scaffold materials. Mesenchymal stem cells are one of the important sources of tissue-engineered skin seed cells. Growth factors optimize the tissue culture environment, and scaffold materials provide appropriate mechanical support. Therefore, how to select appropriate seed cells, growth factors and scaffold materials to construct tissue-engineered skin to treat wounds and speed up repair is the focus and research direction that should be explored in the future. In addition, the development of wound materials is also a new field. Figures and Tables | References | Related Articles | Metrics

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Instructions for Authors (2022) - Chinese Journal of Tissue Engineering Research (CJTER) 2022, 26 (1):  160-164.  doi: 10.12307/2022.027 Abstract ( 504 )   PDF (949KB) ( 791 )   Save Related Articles | Metrics