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08 September 2022, Volume 26 Issue 25 Previous Issue   

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Huo Xue Tong Luo capsule improves osteoblastogenesis of bone marrow mesenchymal stem cells through the ERα-Wnt/β-catenin signaling pathway Wu Zhongshu, Wei Yurou, Chen Xiaojun, Wuri Shana, He Wei, Wei Qiushi 2022, 26 (25):  3937-3943.  doi: 10.12307/2022.395 Abstract ( 1418 )   PDF (4856KB) ( 71 )   Save BACKGROUND: The Huo Xue Tong Luo capsule has been found to prevent the progression of asymptomatic osteonecrosis of the femoral head, but the mechanism is not clear.  OBJECTIVE: To investigate the effect of Huo Xue Tong Luo on the osteoblast differentiation of human bone marrow mesenchymal stem cells, and the effect of ERα-Wnt/β-catenin pathway. METHODS: The third generation of human bone marrow mesenchymal stem cells was cultured in different concentrations of Huo Xue Tong Luo capsule (0, 1, 5, 10 mg/L) for 14 days. Alizarin red staining and alkaline phosphatase activity assay were used to determine the optimal concentration of Huo Xue Tong Luo in promoting osteogenic differentiation of human bone marrow mesenchymal stem cells. Human bone marrow mesenchymal stem cells were further divided into four groups: control group, Huo Xue Tong Luo group, Huo Xue Tong Luo + ICI 182780 group, and Huo Xue Tong Luo + ICI 182780 + DKK1 group. qRT-PCR, western blot assay, and immunofluorescence staining were used to investigate the effect of Huo Xue Tong Luo, ICI 182780 and recombinant human DKK1 protein on osteogenesis of human bone marrow mesenchymal stem cells. RESULTS AND CONCLUSION: (1) Huo Xue Tong Luo capsule (10 mg/L) could significantly promote the proliferation and osteogenic differentiation of human bone marrow mesenchymal stem cells, and promote the mRNA expression of osteogenic genes Runx2, OPN, DLX5, BGLAP, and ERα, as well as the mRNA expression of Wnt/β-catenin pathway related targets β-catenin, TCF7, Lef1, C-MYC, CYCLIN and C-JUN. (2) The osteogenesis of Huo Xue Tong Luo capsule was inhibited by ICI 182780 and DKK1. (3) The results showed that ERα-Wnt/β-catenin signaling pathway was involved in the promoting effect of Huo Xue Tong Luo capsule on the proliferation and osteogenic differentiation of human bone marrow mesenchymal stem cells.  Figures and Tables | References | Related Articles | Metrics

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Chitosan/poly(lactic-co-glycolic acid)/polylactic acid scaffold with sustained release of nerve growth factor promotes the differentiation of bone marrow mesenchymal stem cells into neurons Ji Hangyu, Gu Jun, Xie Linghan, Bao Junping, Peng Xin, Wu Xiaotao 2022, 26 (25):  3974-3979.  doi: 10.12307/2022.401 Abstract ( 564 )   PDF (2484KB) ( 43 )   Save BACKGROUND: More and more evidences demonstrate that nerve growth factor plays important roles in promoting neuronal survival and differentiation. However, nerve growth factor has a short half-life and poor stability, which limits its wide clinical application.   OBJECTIVE: To investigate the feasibility of rat bone marrow mesenchymal stem cells to differentiate into neuronal cells on chitosan/poly(lactic-co-glycolic acid)/polylactic acid scaffolds that can continuously release nerve growth factors. METHODS:  Chitosan/poly(lactic-co-glycolic acid)/polylactic acid scaffolds that sustainably released nerve growth factor and chitosan/poly(lactic-co-glycolic acid)/polylactic acid scaffolds that did not contain nerve growth factor were constructed, and rat bone marrow mesenchymal stem cells were inoculated on the surface of two kinds of scaffolds. The induction program of basic fibroblast growth factor, brain-derived neurotrophic factor and N2 and B27 nerve cell growth additives added to the low-glucose DMEM complete medium was used to induce neurogenesis and differentiation. After 18 days of induction, immunofluorescence staining was used to detect the expression of neuronal markers (microtubule-associated protein 2 and nestin), and western blot assay was utilized to determine the expression of p-TrkA and p-ERK proteins.   RESULTS AND CONCLUSION: (1) After 18 consecutive days of induction, immunofluorescence detection displayed that the microtubule-associated protein 2-positive cells were approximately 30% in the blank scaffold group, and approximately 70% in the sustained release nerve growth factor group. Nestin-positive cells were 40% in the blank scaffold group, and approximately 60% in the sustained release nerve growth factor group. The difference between the two groups was significant. (2) Western blot assay exhibited that the expression levels of p-TrkA and p-ERK in the sustained release nerve growth factor group were significantly higher than those of the blank scaffold group. (3) The results have confirmed that on the surface of the chitosan/poly(lactic-co-glycolic acid)/polylactic acid scaffold that continuously releases nerve growth factor, bone marrow mesenchymal stem cells can achieve better differentiation of neuronal cells through the TrkA/ERK pathway. Figures and Tables | References | Related Articles | Metrics

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LncRNA-HOTAIR can regulate differentiation of adipose derived mesenchymal stem cells into osteoblasts Huang Tao, Jia Zhiqiang, Zhao Xiaoguang, Wang Lei, Fang Liping, Zhai Wenjing, Zhai Shafei, Zhou Yongxin 2022, 26 (25):  3951-3955.  doi: 10.12307/2022.397 Abstract ( 444 )   PDF (1622KB) ( 69 )   Save BACKGROUND: Evidence has shown that LncRNA-HOTAIR can regulate the expression of osteogenic related genes in bone marrow mesenchymal stem cells, but its effect on the osteogenic differentiation of adipose derived mesenchymal stem cells has not been reported. OBJECTIVE: To investigate the effect of LncRNA-HOTAIR on the osteogenic differentiation of adipose derived mesenchymal stem cells.  METHODS: Adipose derived mesenchymal stem cells of Lewis rats were cultured in vitro. LncRNA-NC, lncRNA-HOTAIR mimics, and lncRNA-HOTAIR inhibitor were transfected into adipose derived mesenchymal stem cells and osteogenesis was induced. The alkaline phosphatase activity was detected on the 7th day of osteogenic induction. Alizarin red staining was performed on the 14th day of osteogenic induction. On the 6th day of osteogenic induction, the expression levels of osteogenic-related genes alkaline phosphatase, Runt-related transcription factor 2, osteocalcin, and osteopontin mRNA and protein were detected by RT-PCR and western blot assay. RESULTS AND CONCLUSION: (1) After LncRNA-HOTAIR mimic transfection, alkaline phosphatase activity and calcification degree of adipose derived mesenchymal stem cells were significantly decreased, while LncRNA-HOTAIR inhibitor transfection significantly increased (P < 0.05). (2) After LncRNA-HOTAIR mimic transfection, the expression of alkaline phosphatase, Runt-related transcription factor 2, osteocalcin, and osteopontin in adipose derived mesenchymal stem cells decreased significantly (P < 0.05), but increased significantly after LncRNA-HOTAIR inhibitor transfection (P < 0.05). (3) These results suggest that LncRNA-HOTAIR can negatively regulate the osteogenic differentiation of adipose derived mesenchymal stem cells. Figures and Tables | References | Related Articles | Metrics

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Biological characteristics of adipose-derived mesenchymal stem cells in diabetic patients and their effect on promoting wound healing Xu Manman, Ji Zhe, Ou Lingdong, Li Ang, Shen Caiqi, Jin Peisheng 2022, 26 (25):  3956-3960.  doi: 10.12307/2022.398 Abstract ( 560 )   PDF (1714KB) ( 62 )   Save BACKGROUND: Effective intervention for the mechanism of insufficient cell activity of adipose-derived mesenchymal stem cells in diabetic patients is an important prerequisite for effectively promoting the healing of diabetic wounds.   OBJECTIVE: To observe the biological characteristics of adipose-derived mesenchymal stem cells from diabetic patients and the effect of promoting wound healing. METHODS:  Adipose-derived mesenchymal stem cells were obtained from the abdominal fat of normal people and diabetic patients of the same age and sex. Flow cytometry and cell scratch experiment were used to analyze the apoptosis and migration of the two groups of cells. The levels of hepatocyte growth factor, basic fibroblast growth factor, and vascular endothelial growth factor were detected by ELISA in the two groups. A diabetic nude mouse wound model was prepared; adipose-derived mesenchymal stem cell suspensions from different sources were intradermally injected into the edge of the diabetic nude mouse wound. Cell survival was detected with the LB983 in vivo imaging system at 0, 12, and 24 hours after transplantation. The back healing of nude mice was observed at 7 and 14 days after transplantation.   RESULTS AND CONCLUSION: (1) Compared with the normal group, the cell apoptosis rate in the diabetes group was significantly increased (P < 0.05); the migration distance at 24 hours was significantly reduced (P < 0.05); the secretion levels of cytokines hepatocyte growth factor, fibroblast growth factor β, and vascular endothelial growth factor were significantly reduced (P < 0.05). (2) At 24 hours after cell transplantation, the number of living cells in the diabetic group was significantly reduced compared with the normal group (P < 0.05). After 14 days, the back skin healing of the nude mice in the normal group was better than that in the diabetic group. (3) The results showed that the biological activity of adipose-derived mesenchymal stem cells from diabetic patients decreased, and the effect of promoting wound healing was poor. Figures and Tables | References | Related Articles | Metrics

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Mechanism of human umbilical cord mesenchymal stem cells to promote platelet plasma coagulation Liu Chao, Zhang Lijun, Du Xinjie, Xu Qian, Lü Hongjuan, Fan Dongmei, Tian Huanling, Huang Jian, Huang Yuxiang 2022, 26 (25):  4010-4015.  doi: 10.12307/2022.407 Abstract ( 880 )   PDF (1553KB) ( 55 )   Save BACKGROUND: With the in-depth study of clinical application of mesenchymal stem cell, the clinical use of mesenchymal stem cell has gradually changed. To enhance the role of mesenchymal stem cell in local tissues, stem cell is generally used in combination with local injection of gel, and autologous platelet-rich plasma is an ideal gel replacement material.  OBJECTIVE: To explore the mechanism of human umbilical cord mesenchymal stem cells to promote platelet plasma coagulation. METHODS: (1) Stem cell was mixed with anticoagulated plasma. Calcium chloride was used to stimulate coagulation. Clotting time was recorded. The effect of the number of human umbilical cord mesenchymal stem cells on the clotting time of plasma was analyzed. (2) CD142 expression in stem cell was analyzed by flow cytometry. CD142 antibody was used to pretreat human umbilical cord mesenchymal stem cells and to ensure if CD142 was one of the most important factors to improve plasma coagulation. (3) CD142 expressing model and regulation model were analyzed by checking on database. WGCNA and text mining were used to achieve the result why CD142 gene expression level was high in human umbilical cord mesenchymal stem cells. RESULTS AND CONCLUSION: (1) Platelet plasma coagulation could be accelerated by CD142 expression of human umbilical cord mesenchymal stem cells. CD142 expression was enhanced as the increase in mesenchymal stem cell passage. (2) CD142 upregulation was a result of mesenchymal stem cell autocrine. (3) CD142 could affect the ability of cell chemotaxis and colonization in human umbilical cord mesenchymal stem cells. Figures and Tables | References | Related Articles | Metrics

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Tracing transplanted bone marrow mesenchymal stem cells in rat calvarial defect by bioluminescence imaging Zeng Yuwei, Huang Chuang, Wei Jianguo, Duan Dongming, Wang Le 2022, 26 (25):  3968-3973.  doi: 10.12307/2022.400 Abstract ( 495 )   PDF (1751KB) ( 45 )   Save BACKGROUND: Bioluminescence imaging is an emerging in vivo imaging technology, but there are few studies on the tracing of stem cells after transplantation into living animals in existing reports. OBJECTIVE: To explore the multiplicity of infection of rat derived bone marrow mesenchymal stem cells transfected with Luciferase lentivirus, and further study the effectiveness and stability of Luciferase + bone marrow mesenchymal stem cells in vitro and the tracing effect in rat calvarial defects.  METHODS: The logarithmic growth phase of rat bone marrow mesenchymal stem cells was transfected with different multiplicities of infection, and the fluorescence value was quantitatively analyzed in the in vivo imaging system to determine the optimal multiplicity of infection. Luciferase + bone marrow mesenchymal stem cells were transfected under optimal conditions, and fluorescence values corresponding to different numbers of cells and different passages were analyzed to assess the effectiveness and stability of Luciferase + bone marrow mesenchymal stem cells. Finally, Luciferase + bone marrow mesenchymal stem cells were traced in the rat calvarial defect model.    RESULTS AND CONCLUSION: (1) When the multiplicity of infection increased in the interval of 10-50, the fluorescence quantification increased with the same proportion of multiplicity of infection. The fluorescence quantification did not increase significantly when the multiplicity of infection increased to 100, demonstrating that the optimal multiplicity of infection of Luciferase lentivirus transfected bone marrow mesenchymal stem cells was 50. (2) Luciferase + bone marrow mesenchymal stem cells had a good cell-bioluminescence dose-response relationship and proliferation stability in vitro, demonstrating that fluorescence quantification can indicate the relative number of cells. (3) The transplanted Luciferase + bone marrow mesenchymal stem cells were locally distributed in the skull defect, and the biofluorescence intensity decreased over time and finally disappeared after 35 days. (4) Bioluminescence imaging is an efficient and sensitive technique for tracing stem cells in vivo, which is helpful to characterize the distribution and quantity changes of transplanted stem cells, and provides strong evidence for explaining stem cell function and mechanism research. Figures and Tables | References | Related Articles | Metrics

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Tail vein injection of bone marrow mesenchymal stem cells for repair of skull injury in aging mice Zhang Jingying, Li Ziyi, Liu Xiaochuan, Li Dan, Wang Yang, Wu zhuguo 2022, 26 (25):  3944-3950.  doi: 10.12307/2022.396 Abstract ( 624 )   PDF (2880KB) ( 31 )   Save BACKGROUND: Local application of bone marrow mesenchymal stem cells has the ability to promote bone tissue regeneration and repair; however, whether it could play a significant role via vein injection and its ability of bone tissue regeneration and repair at different ages still need to be clarified.   OBJECTIVE: To explore the effects of bone marrow mesenchymal stem cells on the repair ability of skull injury in young and aging mice via vein injection. METHODS:  Totally 40 1-month-old Kunming mice were obtained as young mice, and 40 12-month-old Kunming mice were obtained as aging mice. The mice were divided into young experimental group, young control group, aging experimental group, and aging control group. The bone defect was made in the cranium of the mice. At 1, 8, and 15 days after surgery, 0.2 mL bone marrow mesenchymal stem cell suspension (1×1010 L-1) was injected into the tail vein of mice in the experimental groups; meanwhile, an equal volume of saline was used in the control groups via tail vein. The mice were sacrificed at 1 and 3 weeks after surgery. The specimens were repaired for the following experiments: morphological, histopathological, optical, and immunohistochemical analyses.   RESULTS AND CONCLUSION: (1) Micro-CT imaging: At 1 week after surgery, there was no significant difference in the size of bone defect area between the young and aging groups, and the size of the bone defect area was reduced significantly in the experimental groups at 3 weeks after surgery. (2) Hematoxylin-eosin staining and Masson staining: The collagen fibers appeared at 1 week after surgery; meanwhile, the bone matrix emerged at 3 weeks after surgery in the defect area. The collagen fibers and the bone matrix were significantly more in the experimental groups than those in the control groups. (3) Non-linear light microscopy: At 3 weeks after the operation, the comparison of collagen content in the defect area was as follows: young experimental group > young control group; aging experimental group > aging control group. (4) Immunohistochemical analysis: At 1 and 3 weeks after operation, Sirt1 protein expression was more in the young groups than that in the aging groups. At 1 week, the Sirt1 protein expression was more in the experimental groups than that in the control groups. At 3 weeks, the Sirt1 protein expression was less in the aging experimental group than that in the aging control group. (5) It is concluded that bone marrow mesenchymal stem cells promoted the repair of skull defects in the mice of different ages significantly via the tail vein injection, which mainly promotes bone regeneration by activating Sirt1 expression in mice. Figures and Tables | References | Related Articles | Metrics

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First-trimester human decidual mesenchymal stem cells combined with tanshinone IIA in the treatment of intrauterine adhesions in rats Xu Weijun, Hu Xiangdan, Yu Dongqing 2022, 26 (25):  3986-3992.  doi: 10.12307/2022.403 Abstract ( 615 )   PDF (2819KB) ( 47 )   Save BACKGROUND: First-trimester human decidual mesenchymal stem cells and tanshinone IIA have anti-adhesion effect, and both have a certain effect on intrauterine adhesion, but the specific mechanism needs to be further studied.   OBJECTIVE: To explore the efficacy and mechanism of first-trimester human decidual mesenchymal stem cells combined with tanshinone IIA in the treatment of intrauterine adhesions. METHODS:  First-trimester human decidual mesenchymal stem cells were isolated and cultured by collagenase I digestion. A total of 45 female SD rats aged 4-6 weeks were randomly divided into 5 groups with 9 rats in each group: control group, model group, tanshinone group, stem cell group and combined treatment group. Sham operation was performed in the control group, and no intervention was performed in the model group after modeling. In the stem cell group, 0.2 mL human decidual mesenchymal stem cell suspension (1×109 L-1) was injected parauterine 7 days after modeling, once every other 3 days, for a total of 3 times. In the tanshinone group, tanshinone IIA solution at 11 mg/(kg·d) was given via intragastulation for 1 week. The combined treatment group received the combination of the above two treatment methods. In the control group and model group, samples were obtained at 5, 10, and 15 days after operation and sham operation. In each treatment group, samples were taken at 5, 10, and 15 days after the last treatment. Hematoxylin-eosin staining and Masson staining were performed to observe the healing degree of the damaged uterus. Serum vascular endothelial growth factor and E2 levels were detected by ELISA. q-PCR was used to detect the expression of miR-29a mRNA in uterine tissue. The protein expression levels of transforming growth factor β1, Smad3 and matrix metalloproteinase 9 were detected by western blot assay.   RESULTS AND CONCLUSION: (1) Compared with the control group, the endometrial fibrosis area ratio in the model group increased significantly (P < 0.05), while the endometrial thickness and the number of glands decreased significantly (P < 0.05). Compared with the model group, the degree of endometrial fibrosis in the combined treatment group was significantly lower (P < 0.05) and the thickness of the intima and the number of glands increased significantly (P < 0.05). The endometrial fibrosis area ratio of rats in the stem cell group and the tanshinone group also decreased significantly (P < 0.05). (2) Compared with the model group, the serum estrogen E2 level of the tanshinone, stem cell and the combined treatment groups was significantly increased (P < 0.05); vascular endothelial growth factor level was significantly decreased (P < 0.05); the expression of miR-29a mRNA was significantly increased (P < 0.05); the expression of transforming growth factor β1 and Smad3 protein in the combined treatment group was significantly decreased (P < 0.05), and the expression of matrix metalloproteinase 9 protein in the tanshinone group was significantly increased (P < 0.05). (3) Results suggest that the combined treatment of first-trimester human decidual mesenchymal stem cells and tanshinone IIA can effectively repair the endometrium in rats, and the mechanism may be through the regulation of miR-29a to reduce the levels of transforming growth factor β1 and Smad3 protein, and then improve the fibrosis. Figures and Tables | References | Related Articles | Metrics

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Hypoxia-treated dental pulp stem cell exosomes induce M2 macrophage polarization Tan Xu, Liang Yu, Liang Yan, Liao Jian 2022, 26 (25):  3961-3967.  doi: 10.12307/2022.399 Abstract ( 866 )   PDF (1481KB) ( 66 )   Save BACKGROUND: Studies have found that human dental pulp stem cells can treat periapical periodontitis bone defects under hypoxia preconditioning, but whether dental pulp stem cell exosomes under hypoxia preconditioning can carry the biological information of blasts and affect polarization of macrophages is unclear.   OBJECTIVE: To study the effect of hypoxia-treated dental pulp stem cells exosomes on macrophage polarization. METHODS:  Passage 3 dental pulp stem cells were cultured in a normal and hypoxic incubator. The medium was replaced once every 48 hours. Cell culture supernatants were collected at the confluence of 80%-90%. Exosomes were extracted by differential centrifugation. Human monocyte cell line THP-1 was induced to differentiate into macrophages, and co-incubated with PBS, normal culture, and hypoxic cultured dental pulp stem cells for 48 hours. Levels of inflammatory factors interleukin 10 and tumor necrosis factor alpha in supernatant were detected using ELISA. RT-qPCR was utilized to detect macrophage CD163, interleukin 1 receptor antagonist, transforming growth factor β1, chemokine CCL2, and tumor necrosis factor α mRNA expression. Flow cytometry was utilized to detect the expression of CD11b+CD163+ macrophages. Western blot assay was used to detect the activation of NF-κB and STAT3 signaling pathways.   RESULTS AND CONCLUSION: (1) Compared with the PBS group, the level of interleukin-10 in the supernatant of macrophages in the normal cultured dental pulp stem cell-derived exosomes group significantly increased (P < 0.05), and the level of tumor necrosis factor alpha significantly reduced (P < 0.05). The expression of CD163, transforming growth factor β1, and chemokine CCL2 mRNA in macrophages increased significantly (P < 0.05); the expression of tumor necrosis factor alpha mRNA decreased significantly (P < 0.05), and the positive rate of CD11b+CD163+ macrophages increased significantly (P < 0.05); the phosphorylation level of p65 significantly reduced (P < 0.05); the expression of IκBα significantly increased (P < 0.05), and the phosphorylation level of STAT3 also significantly increased (P < 0.001). (2) Compared with the normal cultured dental pulp stem cell-derived exosomes group, the level of interleukin-10 in the supernatant of macrophages significantly increased in the hypoxic cultured dental pulp stem cell-derived exosomes group (P < 0.001), and the level of tumor necrosis factor alpha significantly reduced (P < 0.01); CD163, transforming growth factor β1, chemokine CCL2 and interleukin 1 receptor antagonist mRNA expression significantly increased (P < 0.01); tumor necrosis factor alpha mRNA expression also significantly decreased (P < 0.01); the positive rate of CD11b+CD163+ macrophages significantly increased (P < 0.01); the phosphorylation level of p65 significantly reduced (P < 0.01); the expression of IκBα significantly increased (P < 0.01), and the phosphorylation level of STAT3 significantly increased (P < 0.01). (3) It is concluded that normal culture and hypoxic culture of exosomes derived from dental pulp stem cells can promote the M2 polarization of macrophages, and the M2 polarization of macrophages is more obvious under hypoxic culture, and its mechanism may be to activate the STAT3 signaling pathway and inhibit the NF-κB signaling pathway. Figures and Tables | References | Related Articles | Metrics

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Comparison of effects of exosomes secreted by different mesenchymal stem cells for the treatment of osteoarthritis Wang Xianfeng, Ou Xin, Deng Biyong 2022, 26 (25):  3980-3985.  doi: 10.12307/2022.402 Abstract ( 601 )   PDF (2100KB) ( 115 )   Save BACKGROUND: Mesenchymal stem cells, as seed cells in tissue engineering, have shown powerful curative effect for the treatment of osteoarthritis in the past few decades, and many registered clinical experiments have been carried out in China. More studies have shown that mesenchymal stem cells that play a therapeutic role in vivo release exosomes through paracrine function.   OBJECTIVE: To compare the effect of bone marrow mesenchymal stem cell exosomes and umbilical cord mesenchymal stem cell exosomes on the treatment of osteoarthritis. METHODS:  Bone marrow mesenchymal stem cell exosomes and umbilical cord mesenchymal stem cell exosomes were isolated by ultra-centrifugation. Nanosight, transmission electron microscopy, and western blot assay were used to identify exosomes. Chondrocytes were co-cultured with interleukin-1β to simulate osteoarthritis in vitro. The effects of bone marrow mesenchymal stem cell exosomes and umbilical cord mesenchymal stem cell exosomes on the proliferation, apoptosis and extracellular matrix secretion of chondrocytes were evaluated by CCK-8 assay, western blot assay, and qPCR. Collagen II collagenase was injected to induce rat osteoarthritis model and the efficacy of in vivo injection of exosomes was evaluated by macroscopic evaluation and histological staining. The concentrations of interleukin-1β and tumor necrosis factor-α of joint fluid were examined by ELISA.   RESULTS AND CONCLUSION: (1) Both kinds of exosomes were cup-shaped or round-shaped with particle size of 105-120 nm, and expressed characteristic proteins CD63, CD81, and TSG1010. (2) The yield and purity of umbilical cord mesenchymal stem cell exosomes were higher than those of bone marrow mesenchymal stem cell exosomes. (3) Both exosomes could alleviate the inflammatory effect of interleukin-1β on chondrocytes, which was mainly manifested in promoting proliferation, inhibiting apoptosis, and increasing the secretion of extracellular matrix. Among them, umbilical cord mesenchymal stem cell exosomes had stronger cartilage repair activity. (4) After the treatment of both exosomes, the macroscopic performance and OARSI score of articular cartilage were better than those of the control group, and the inflammatory factors in the joint fluid were decreased, among which the efficacy of umbilical cord mesenchymal stem cell exosomes was better than that of bone marrow mesenchymal stem cell exosomes. (5) Results suggest that the yield and purity of umbilical cord mesenchymal stem cell exosomes are higher than that of bone marrow mesenchymal stem cell exosomes, and the therapeutic effect of umbilical cord mesenchymal stem cell exosomes on the treatment of osteoarthritis is better than that of bone marrow mesenchymal stem cell exosomes. Therefore, umbilical cord mesenchymal stem cell exosome is more suitable as a new strategy for osteoarthritis. Figures and Tables | References | Related Articles | Metrics

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Effect of N-arachidonylethanolamine on axon regeneration of the dorsal root ganglion Zhang Haonan, Wang Xingran, Li Meimei, Ma Jinjin, Ma Yanxia, Saijilafu 2022, 26 (25):  3999-4003.  doi: 10.12307/2022.405 Abstract ( 450 )   PDF (1303KB) ( 35 )   Save BACKGROUND: Nerve axon regeneration is mainly affected by its own regenerative ability and inhibitory external environment. N-arachidonylethanolamine has been proven to regulate axon regeneration in C. elegans, but its role in mammals is still unknown.   OBJECTIVE: To explore the effect of N-arachidonylethanolamine on axon regeneration of mouse dorsal root ganglion neurons. METHODS:  Dorsal root ganglion tissues were taken from L4-L5 of ICR mice aged 6-8 weeks, digested with collagenase and trypsin, and divided into URB597 group, N-arachidonylethanolamine group, methyl-sulfoxide control group, and electroporated green fluorescent protein and specific siRNA mixture group. After 3 days of in vitro culture, the axons were labeled by neuron-specific immunoassay. Axon length, and the number of primary and secondary branches were measured, and the statistics was performed to determine the regulatory effect of N-arachidonylethanolamine on the regeneration of dorsal root ganglion neuron axon.   RESULTS AND CONCLUSION: (1) After inhibiting fatty acid amide hydrolase activity, there was no obvious change in dorsal root ganglion cell axon regeneration and URB597 had no cytotoxic effect on dorsal root ganglion neuron cells (P > 0.05). (2) After fatty acid amide hydrolase knockdown, dorsal root ganglion cell axon regeneration had no obvious change (P > 0.05). (3) Exogenous N-arachidonylethanolamine had no obvious regulatory effect on dorsal root ganglion cell axon regeneration and N-arachidonylethanolamine had no cytotoxic effect on dorsal root ganglion neuron cells (P > 0.05). (4) Inhibiting fatty acid amide hydrolase activity or adding exogenous N-arachidonylethanolamine has no effect on dorsal root ganglion neuron axon branches (P > 0.05). Figures and Tables | References | Related Articles | Metrics

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Expression of leptin receptor in mouse skin and the role of leptin receptor-positive cells in skin development and wound healing Wang Ao, Chu Hongshang, Wu Hongguang, Li Ke, Liu Huijuan 2022, 26 (25):  3993-3998.  doi: 10.12307/2022.404 Abstract ( 537 )   PDF (13011KB) ( 72 )   Save BACKGROUND: It is believed that leptin receptor (LepR) marks the adult bone marrow mesenchymal stem cells in mice and LepR+ cells contribute to the regeneration of fractured bone. However, the residence of LepR+ stromal cells in skin and the function of the population in skin development and repair are poorly understood.   OBJECTIVE: To investigate the expression of LepR in mouse skin and the role of LepR+ cells in development and tissue repair. METHODS:  The study was approved by the Experimental Animal Ethics and Use Committee of Shanghai Jiao Tong University with the approval No. 1504002. The LepR-Cre; tdTomato mice were generated by using the classic Cre-loxP system for tracing the expression of LepR in mouse skin. Flow cytometry was used to analyze surface markers on Tomato+ cells. A full-thickness skin excision wound model was constructed on the back of LepR-Cre; tdTomato mice to trace the distribution of LepR+ cells in skin wound healing. The LepR-Cre; Tsc1fl/fl mice for specific deletion of Tsc1 in LepR+ cells were constructed to identify the role of Tsc1 in mouse skin development.   RESULTS AND CONCLUSION: (1) LepR was expressed in dermal papilla, stroma, and dermal white adipose tissue in mice skin. (2) Immunofluorescence staining revealed that LepR+ cells partially co-expressed with stromal marker Vimentin and adipocyte marker Perilipin. Cell surface marker analysis showed that LepR lineage cells were negative for CD11b, CD45, and CD31, and positive for CD73 and Sca-1. LepR labeled a population of mesenchymal stem cells in mouse skin. (3) Punching experiment of LepR-Cre; tdTomato mice uncovered that LepR+ cells were involved in injury repair. (4) The LepR-Cre; Tsc1fl/fl mice presented the phenotype that the thickness of dermis and dermal white adipose tissue increased and the number of adipocytes increased significantly. It is concluded that LepR is expressed in mouse skin and cells of the LepR lineage in the skin are involved in tissue development and damage repair. Figures and Tables | References | Related Articles | Metrics

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Roles of F-actin and myosin II in the regulation of cell mechanics Fan Jiayu, Xu Limeng, Liu Yang, Wang Li 2022, 26 (25):  4004-4009.  doi: 10.12307/2022.406 Abstract ( 617 )   PDF (2274KB) ( 95 )   Save BACKGROUND: At present, the roles of actin and myosin II, two important cytoskeletal proteins, have been widely studied, but their roles in the regulation of cell mechanics are still incomplete.   OBJECTIVE: To elucidate the roles of actin and myosin in the regulation of cell mechanical properties. METHODS:  The surface elastic modulus of the long axis and short axis terminal regions of the HeLa cells over time was measured by atomic force microscopy. The Cytochalasin D (inhibitor of actin polymerization), blebbsitatin (inhibitor of ATPase of myosin II) and Calysulin A (enhancer of the myosin II contractive activity) were used to treat HeLa cells. The F-actin, myosin II and activation characteristics of Rho A in HeLa cells were analyzed by confocal microscope.   RESULTS AND CONCLUSION: (1) In the inhibitor treatment group, the surface elastic modulus at the long axis and short axis terminal regions showed a trend changes, and the change of opposite terminal regions modulus was inconsistent. (2) Inhibition of F-actin polymerization decreased the surface elastic modulus, but the enhancement of myosin II contraction activity significantly increased the surface elastic modulus. (3) The surface elastic modulus increased with F-actin aggregation, and regulated by Rho A activation, but it did not change with the aggregation of myosin. (4) The results showed that the changes of mechanical properties of cells caused by actin and myosin II were not only numerical changes, but also asymmetric changes of mechanical properties. These changes were regulated by the distribution of actin fibers and the contractile activity of myosin II. Figures and Tables | References | Related Articles | Metrics

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Mechanism and characteristics of mechanical microenvironment of extracellular matrix and intercellular interaction Min Ziyang, Munire·Aili, Zheng Yunhao, Zeng Xingzhi, Bian Nanyan, Deng Shuangshan, Xie Jing 2022, 26 (25):  4034-4045.  doi: 10.12307/2022.411 Abstract ( 1046 )   PDF (1943KB) ( 204 )   Save BACKGROUND: Mechanical properties of cellular extracellular matrix play a key role in human organ development, physiological function maintenance and disease occurrence by guiding cell adhesion, migration, proliferation and differentiation. In regenerative medicine and stem cell therapy, mechanical factors in extracellular matrix can direct the survival, growth, proliferation and differentiation of the implanted cells, which dictates cell fate of the implanted cells and determines the success of tissue regeneration and stem cell therapy.  OBJECTIVE: To review the effects of mechanical signals of extracellular matrix microenvironment on cell behavior, including cytoskeleton reconstruction, migration, proliferation, differentiation and intercellular communication, and elucidate the existing molecular regulation mechanism in order to provide theoretical support for the practical transformation of the interaction between cells and their mechanical microenvironment in tissue engineering and stem cell therapy. METHODS: The articles were searched on PubMed, CNKI, and Wanfang databases with the key words of “cytoskeleton, cell spreading, cell migration, cell proliferation, cell differentiation, cell communication, mechanotransduction, stiffness of substrate, surface topography, extracellular matrix, matrix” in Chinese and English, respectively. Finally, 161 articles met the criteria for review. RESULTS AND CONCLUSION: Various mechanical signals of extracellular matrix, such as material interface stiffness, topology and hydrophilicity/hydrophobicity, regulate cell expansion, proliferation, migration, differentiation, communication and other special physiological properties from mechanical recognition, mechanochemical signal transduction, signal pathway cascade, downstream protein activation, and transcriptional initiation to protein expression. It is of great significance for directional culture of cells in tissue engineering and cell targeted therapy in clinical medicine. Figures and Tables | References | Related Articles | Metrics

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Preparation and sterilization method of human acellular amniotic membrane scaffold He Qi, Xu Faya, Li Xiyan, Han Lei, Xiao Yanbing, Tu Jiao 2022, 26 (25):  4028-4033.  doi: 10.12307/2022.410 Abstract ( 570 )   PDF (10078KB) ( 69 )   Save BACKGROUND: Human acelluar amniotic membrane is a natural scaffold material, which obtains from the decellularization of fresh human amniotic membrane by physical, chemical and biological methods. It is rich in collagen, proteoglycan, glycoprotein, growth factor, extracellular matrix and so on. Human acelluar amniotic membrane has the advantages of good biocompatibility, natural three-dimensional structure, low immunogenicity, small rejection reaction, easy sampling and so on. Therefore, it is widely used in skin, cornea, bone tissue repair and peripheral nerve regeneration.   OBJECTIVE: To achieve optimal decellularization by comparing the advantages and disadvantages of different preparation methods of human acelluar amniotic membrane and combined all the methods together. METHODS: The articles were searched in Wanfang, CNKI, and PubMed databases published from 2000 to 2020. The key words were “amniotic membrane, acelluar amniotic membrane, decellularized amniotic membrane, decellularized human amniotic scaffolds, sterilization of amniotic membrane, tissue engineering” in Chinese and English. Finally, 56 articles were included for review.  RESULTS AND CONCLUSION: Nowadays, all the preparation methods of human acelluar amniotic membrane have their own advantages and disadvantages. Although all of them can effectively remove most of the cell components, they also adversely affect residual extracellular matrix composition, biological activity, intact basement membrane, biomechanical properties and so on. Therefore, it is necessary to complement the advantages and disadvantages of different preparation methods to improve the efficiency of decellularization. Common combination methods are chemical and biological combination, physical and chemical combination, physical and chemical/biological combination to decellularize together. Among them, the most effective method is the combination of chemical, biological (enzyme) and physical methods. First, chemical detergents were used to destroy cell membranes, and then enzyme was used to separate cell components from extracellular matrix. Finally, physical methods, such as scraping and shaking, were used to improve the efficiency of decellularization. In the end, the cells can be completely eliminated and a relatively complete extracellular matrix can be retained. Figures and Tables | References | Related Articles | Metrics

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Key problems of preparation and quality control of human amniotic mesenchymal stem cells pharmaceutics Wang Yuying, Yu Limei 2022, 26 (25):  4016-4021.  doi: 10.12307/2022.408 Abstract ( 546 )   PDF (1152KB) ( 44 )   Save BACKGROUND: Human amniotic mesenchymal stem cells are a kind of the ideal seed cells in the field of regenerative medicine. Human amniotic mesenchymal stem cells have shown good application prospect in the treatment of a variety of diseases. Effective control of the key technology of preparation process to ensure that human amniotic mesenchymal stem cells preparations meet the quality requirements is fundament for the safety and effectiveness of clinical application.  OBJECTIVE: To describe the key technologies of human amniotic mesenchymal stem cells preparation and quality control, analyze the existing problems and solutions, and summarize the key quality control and technical standards. METHODS: CNKI, Wanfang, and PubMed databases were retrieved by using computer to search relevant articles published from January 2010 to March 2021 with key words of “mesenchymal stem cells, cell culture, biological characteristic, quality control, microbiology contamination” in Chinese and English, separately. Finally, 47 articles were included for analysis. RESULTS AND CONCLUSION: It is the key to quality control and ensure safety in clinic, for example, (1) scientific selection of donors during the preparation of clinical-grade human amniotic mesenchymal stem cells; stable and standardized collection methods; optimization of cell separation, culture, and in vitro expansion techniques, standardization of experimental operations; monitoring of cell preparation laboratory environment, and cell preparation quality detection technology and so on.  (2)  The establishment and application of a serum-free culture system are conducive to ensuring the quality of preparations. (3) Maintaining the biological characteristics and functional activity of human amniotic mesenchymal stem cells, as well as human amniotic mesenchymal stem cells tumorigenicity, aging, and abnormal immune response meet the release and review inspection quality standards. These can ensure that human amniotic mesenchymal stem cells preparations exert good clinical effects and avoid adverse reactions to the greatest extent. Figures and Tables | References | Related Articles | Metrics

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Effect and mechanism of human amniotic epithelial cells on nerve injury repair Wang Kang, Zhi Xiaodong, Wang Wei 2022, 26 (25):  4046-4051.  doi: 10.12307/2022.412 Abstract ( 624 )   PDF (1127KB) ( 95 )   Save BACKGROUND: Compared with other kinds of stem cells, human amniotic epithelial cells are more primitive in development and stronger in expansion. In particular, they have many advantages, such as wide sources, low acquisition costs and strong controllability. They have an important positive effect on the process of nerve damage repair, which is a kind of “seed cell” with wide application prospects.  OBJECTIVE: To summarize the application effect of human amniotic membrane epithelial cells in the treatment of nerve injury, and provide reference and basis for the treatment of clinical nerve injury. METHODS: Articles in PubMed database from 2000 to 2020 were searched using the search terms of “central nervous system injury, peripheral nerve injury, amniotic epithelial cells, cell therapy, tissue engineering, genetic engineering, repair, regenerate”. Articles in databases of CNKI, VIP and Wanfang from 2000 to 2020 were retrieved with the search terms of “central nervous system injury, peripheral nerve injury, human amniotic epithelial cells, cell therapy, tissue engineering, genetic engineering, repair, regenerate”. The literature and references were reviewed one by one. RESULTS AND CONCLUSION: Human amniotic epithelial cells have strong nerve tissue repair, regeneration and protection capabilities, which can avoid immune rejection and tumorigenic risks that occur during other stem cell transplantation. They are one of the reliable cell sources for the treatment of neurological diseases. Future research is not only needed to deepen its basic biological characteristics, but also needs to be further developed in differentiation ability. Figures and Tables | References | Related Articles | Metrics

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Immune reconstruction and anti-cytomegalovirus immunity of mesenchymal stem cells after transplantation Chen Dabing, Yang Ting 2022, 26 (25):  4052-4057.  doi: 10.12307/2022.413 Abstract ( 454 )   PDF (1090KB) ( 34 )   Save BACKGROUND: Allogeneic hematopoietic stem cell transplantation is the most effective method to cure leukemia and other malignant hematological diseases, severe aplastic anemia, and hereditary hematological diseases. However, immune reconstitution is often delayed in the early stage after transplantation, which significantly increases the risk of cytomegalovirus infection/reactivation. Only promoting early immune reconstitution can produce a cytomegalovirus-specific immune response and truly and effectively control virus replication for a long time.  OBJECTIVE: To summarize the research progress of immune reconstruction and anti-cytomegalovirus immune function of mesenchymal stem cells after transplantation, and analyze the current problems and future development directions.  METHODS: The PubMed database was searched with “allogeneic hematopoietic stem cell transplantation, mesenchymal stem cells, immune reconstruction, CMV” as key words. The search time limit was from 2016 to 2020. Repetitive articles irrelevant to the research purpose of the article were excluded, and 46 articles that met the criteria were included for review.  RESULTS AND CONCLUSION: The restoration of thymus function is beneficial to promote the restoration of the diversity of T cell response pools, and is the key to immune reconstitution and antiviral therapy optimization. The latest progress of immunology indicates that mesenchymal stem cells may have the functions of reversing thymic aging, repairing thymus damage and promoting thymus regeneration, and exert antiviral effects through multiple targets and multiple mechanisms and protect the host from virus attack. However, there are still many limitations. The miR-21 genetically modified mesenchymal stem cells are expected to provide new ideas and new strategies for immune reconstruction and anti-viral immunity after transplantation. These will be the direction of future cell therapy.  Figures and Tables | References | Related Articles | Metrics

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Role of mesenchymal stem cell-derived exosomes in tissue fibrosis repair Tang Jianhong, Zhang Nini, Huang Guilin, Lang Jiachan, Cui Tianning, Luo Qinliang 2022, 26 (25):  4022-4027.  doi: 10.12307/2022.409 Abstract ( 628 )   PDF (1088KB) ( 66 )   Save BACKGROUND: Mesenchymal stem cell replacement therapy has always been regarded as one of effective methods for the treatment of fibrotic diseases. Its safety has been questioned. Exosomes are the paracrine products of mesenchymal stem cells with similar curative effects. This kind of cell-free therapy has now become the focus of researchers. OBJECTIVE: To summarize the role of mesenchymal stem cell-derived exosomes in the repair of lung, liver, heart and kidney fibrosis, and to look into the application of exosomes in the repair of radioactive salivary gland fibrosis. METHODS: PubMed database and CNKI database were retrieved with “exosomes, mesenchymal stem cells, tissue fibrosis, radiation salivary glands, repair” as keywords. Articles were filtered by a quick look at the article title and abstract. The articles that were not closely related to the topic were excluded. This paper finally selected 46 articles in intensive reading and writing.  RESULTS AND CONCLUSION: Exosomes are mainly composed of lipids, proteins, nucleic acids, which have the functions of cell communication, anti-apoptosis, anti-inflammatory, and anti-fibrosis. The extraction methods are diverse and each has its advantages and disadvantages. Mesenchymal stem cell-derived exosomes play an important role in repairing fibrosis damage of the lung, liver, heart, and kidney. However, there are few studies on repairing tissue fibrosis caused by radioactive salivary gland damage, and it is worthy of in-depth study and exploration. Figures and Tables | References | Related Articles | Metrics

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Mesenchymal stem cells promote wound healing by regulating the autophagy Zhang Gaofei, Wang Di, Li Jiamei, Lou Hanxiao, Zeng Yueqin, Liu Wenjun 2022, 26 (25):  4058-4063.  doi: 10.12307/2022.414 Abstract ( 539 )   PDF (1093KB) ( 47 )   Save BACKGROUND: In recent years, the role of mesenchymal stem cells in wound healing has received widespread attention. Although mesenchymal stem cells can promote wound healing, its mechanism of action is not completely clear. OBJECTIVE: To review the role and mechanism of mesenchymal stem cells in promoting wound healing in recent years. METHODS: Using “mesenchymal stem cells, wound healing, autophagy, stem cells” as Chinese and English key words, related articles were searched on PubMed, Cochrane Library, CNKI, VIP, Wanfang Medical Network, China Biomedical Literature Database from the establishment of the database to March 2021.  RESULTS AND CONCLUSION: Mesenchymal stem cells can promote wound healing by regulating autophagy and wound environment. At the same time, as a new method to promote wound healing, mesenchymal stem cells can be used as an ideal autophagy inducer to promote wound healing, promote the proliferation and migration of wound fibroblasts, inhibit inflammatory reaction, and promote the angiogenesis of endothelial cells, so as to promote the healing of injured wounds. However, the mechanism and promotion of mesenchymal stem cells on autophagy are still unclear. Therefore, the research of autophagy elimination and related molecular mechanism caused by mesenchymal stem cell implantation into wound has become the focus of current wound healing research. Figures and Tables | References | Related Articles | Metrics

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Proteoglycans in tooth development and its role in regulating stem cell homeostasis Chen Jiawen, Sun Tianyu, Liu Peng, Wu Buling, Wu Jingyi 2022, 26 (25):  4064-4069.  doi: 10.12307/2022.415 Abstract ( 570 )   PDF (1586KB) ( 62 )   Save BACKGROUND: Tooth regeneration is one of the hot issues in dentistry. The development of tooth regeneration is based on the in-depth understanding of the mechanism of tooth germ development. Previous studies have focused on the exploration of intracellular signaling regulatory networks related to tooth development, but studies on extracellular regulatory molecules have been scarce. As an important component of extracellular matrix and stem cell microenvironment, proteoglycans are involved in signal transduction and mediate the balance between of self-renewal and differentiation of stem cells.  OBJECTIVE: To review the research progress on proteoglycans in tooth development and its roles in mediating stem cell homeostasis and the mechanisms involved, and to prospect its future research focus. METHODS: PubMed, Web of Science and CNKI databases were searched for the articles concerning proteoglycans in regulating stem cell self-renewal homeostasis and tooth development with the search terms of “proteoglycans, glycosaminoglycans, stem cell homeostasis, tooth development, tooth renewal, cell signaling, heparan sulfate, chondroitin sulfate” in English and Chinese. After primarily screening based on the inclusion and exclusion criteria, the articles with high relevance were included for review.   RESULTS AND CONCLUSION: As an important component of extracellular matrix and stem cell microenvironment, proteoglycans are extensively involved in the development of tooth germ and affect the destination of dental stem cells and mesenchymal stem cells. Clarifying the mechanism of proteoglycan in tooth germ development will be beneficial to establishing and perfecting the intracellular and extracellular regulatory signal network related to tooth development and provide a new idea for the study of biological tooth regeneration. Figures and Tables | References | Related Articles | Metrics

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Impact of nicotine on stem cells Zeng Rui, Hai Bing 2022, 26 (25):  4070-4075.  doi: 10.12307/2022.416 Abstract ( 740 )   PDF (1173KB) ( 134 )   Save BACKGROUND: Stem cell therapy has great clinical application potential. Stem cell donor needs to be screened for infectious and genetic diseases before implantation, but some important factors related to lifestyle are often overlooked, especially smoking. For many diseases, smoking is a risk factor. With the increasing use of e-cigarettes, nicotine exposure is becoming serious and widespread. OBJECTIVE: To describe and analyze the effects of nicotine exposure on various types of stem cells. METHODS: Articles were searched on PubMed and CNKI databases published between 1806 and 2021. The search terms were “nicotine, tobacco smoking, stem cells therapy, embryonic stem cells, mesenchymal stem cells, induced pluripotent stem cells, periodontal ligament-derived stem cells” in Chinese and English. A total of 59 articles were selected according to the inclusion and exclusion criteria and summarized.  RESULTS AND CONCLUSION: Nicotine activates nicotinic acetylcholine receptors in embryonic stem cells, mesenchymal stem cells, induced pluripotent stem cells and periodontal membrane stem cells through a variety of mechanisms to affect their proliferation, differentiation, migration and apoptosis. At present, although the research on the effect of nicotine on stem cells is facing severe challenges, it is very necessary to study the effect of nicotine on stem cells, because “healthy stem cells” are the prerequisite for stem cell therapy. Figures and Tables | References | Related Articles | Metrics

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Future of exosomes and mesenchymal stem cell-derived exosomes in the diagnosis and treatment of Parkinson’s disease Wei Yufan, Fan Feiyan, Li Shuangli, Zhang Yunke 2022, 26 (25):  4076-4083.  doi: 10.12307/2022.417 Abstract ( 570 )   PDF (1275KB) ( 91 )   Save BACKGROUND: Exosomes are nano-scale microvesicles that can freely penetrate the blood-brain barrier and are of great values in maintaining the stability of the internal environment, communicating between cells, and regulating immune responses. Mesenchymal stem cells, as the cells with the strongest ability to secrete exosomes, have the advantages of easy collection, low immune rejection, and weak ethical response, and mesenchymal stem cell-derived exosomes can help improve damaged nervous system functions. Inhibiting the apoptosis of dopaminergic neurons is considered to be a promising therapeutic tool for the treatment of Parkinson’s disease. OBJECTIVE: To review the role of exosomes in the pathogenesis of Parkinson’s disease, as diagnostic biomarkers, drug delivery vehicles, and the research progress of mesenchymal stem cell-derived exosomes in the mechanism of Parkinson’s disease.  METHODS: “Exosomes, mesenchymal stem cells, Parkinson disease” were used as the Chinese and English search terms. Relevant articles were searched in CNKI and PubMed from inception to May 2021. The search languages were Chinese and English. According to the inclusion and exclusion criteria, 117 relevant articles were finally included. RESULTS AND CONCLUSION: (1) The definition, source, composition, and function of exosomes, the discovery, definition, mechanism and application of mesenchymal stem cells were summarized. (2) It is concluded that the aggregation of α-synuclein can cause pathological spread, and α-synuclein is found in exosomes, which may be a possible molecular mechanism of the spread of α-synuclein between cells. α-Synuclein can activate microglia in Parkinson’s disease, cause an inflammatory cascade, induce neuritis and dopamine neuron degeneration. Exosomal miRNA can induce changes in the genetic program of target cells. The above-mentioned pathogenesis promotes the progression of Parkinson’s disease. (3) The application of exosomes as diagnostic biomarkers and drug delivery vehicles is summarized. The role of mesenchymal stem cell-derived exosomes in Parkinson’s disease was summarized, mainly in inhibiting inflammation, regulating gene expression, inhibiting dopamine neuron apoptosis, thereby exerting a neuroprotective effect and increasing the release of dopamine. (4) It is found that mesenchymal stem cell-derived exosomes have broad prospects in the diagnosis and treatment of Parkinson’s disease, and are worthy of further in-depth study. Figures and Tables | References | Related Articles | Metrics

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Stem cell transplantation in the treatment of premature ovarian failure: a meta-analysis based on 13 animal studies Zhao Shuying, Guo Guangling, Liu Chenchen, Zhang Chao, Dong Sirui, Gong Qinqin, Ji Luwei 2022, 26 (25):  4084-4092.  doi: 10.12307/2022.418 Abstract ( 552 )   PDF (1470KB) ( 177 )   Save OBJECTIVE: In recent years, the incidence of premature ovarian failure has been on the rise, showing the young trend. Because of the complex etiology of premature ovarian failure and poor clinical outcome, there is an urgent need to find a safe and effective treatment modality. This study systemically assessed the effectivity of stem cell transplantation of premature ovarian failure animal models. METHODS: PubMed, The Cochrane Library, EMbase, CBM, CNKI, Wanfang, and VIP were retrieved before June 10, 2020. A series of studies on the treatment of premature ovarian failure animal models by stem cells were collected. Two evaluators independently screened the literature and extracted the data. The SYRCLE risk of bias assessment scale for animal experiments was used to evaluate the quality of the literature. The primary outcome indicators were analyzed using RevMan 5.3 software for meta-analysis.  RESULTS: (1) A total of 13 randomized controlled animal experimental studies were included, with 348 mice, and overall quality was moderate. Stem cell group (n=184) only received stem cell transplantation, and control group (n=164) only received blank control, normal saline or PBS intervention. (2) Meta-analysis results showed that compared with the control group, serum estrogen level (SMD=3.02, 95%CI: 1.87-4.18, P < 0.000 01), serum anti-Müllerian hormone level (ng/mL subgroup: SMD=4.77, 95%CI: 0.95-8.59, P=0.01; pg/mL subgroup: SMD=4.94, 95%CI: 0.91-8.97, P=0.02), serum luteinizing hormone level (SMD=-1.47, 95%CI: -1.73 to -1.22, P < 0.000 01), the number of follicles at all levels (SMD=1.91, 95%CI: 0.85-2.97, P=0.000 4) and fertility rate increased (RR=2.07, 95%CI: 1.39-3.09, P=0.000 4), but serum follicle-stimulating hormone level decreased (P < 0.000 1) in the stem cell group. The number of follicles at all levels was significantly higher in the stem cell group than that in the control group (P < 0.05). Subgroup analysis showed that with the increase of follow-up time, the number of primordial follicles, primary follicles and secondary follicles was significantly increased (P < 0.05), and the number of atresic follicles was significantly decreased (P < 0.05). Different types of stem cell transplantation could improve the serum estrogen level, and the recovery of serum estrogen level was more significant with the increase of unit dose of stem cell injection (P < 0.05).   CONCLUSION: Available evidence from animal studies suggests that stem cell transplantation is effective in treating premature ovarian failure model mice. Stem cell transplantation induces an increase in estrogen levels, a decrease in follicle-stimulating hormone levels, and an improvement in follicle numbers at all levels in premature ovarian failure. Stem cells have some restorative effects on the ovary, but large samples and high quality human trials are still needed to verify clinical application effects. Figures and Tables | References | Related Articles | Metrics

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Efficacy and safety of human umbilical cord mesenchymal stem cells in the treatment of spinal cord injury: a meta-analysis Shi Yao, Han Shufeng, Yuan Yitong, Du Ruochen, Jing Zhijie, Zhao Bichun, Zhang Ruxin, Zhang Yujuan, Wang Chunfang 2022, 26 (25):  4093-4100.  doi: 10.12307/2022.419 Abstract ( 872 )   PDF (1385KB) ( 57 )   Save OBJECTIVE: There is still a lack of effective treatments for spinal cord injury. Cell therapy could be a promising treatment method, in which human umbilical cord mesenchymal stem cells have received wide attention, because of its easy availability, low cost, less ethical issues, and low immunogenicity. At present, it has not been widely used in clinical practice, and its effectiveness and safety are still controversial. A meta-analysis was used to evaluate the efficacy and safety of human umbilical cord mesenchymal stem cells in the treatment of spinal cord injury. METHODS: We searched English databases (PubMed, Web of Science, Cochrane, and EMbase) and Chinese databases (CNKI, Wanfang Medical Network, and VIP), and collected clinical articles on human umbilical cord mesenchymal stem cells in the treatment of spinal cord injury. The retrieval period was from the establishment of the database to April 2021. Two investigators independently read the included studies, extracted the data, and assessed the quality. The randomized controlled trials were scored using the modified Jadad scoring scale, and the Cochrane risk bias assessment tool was used to assess the risk of bias. The cohort studies were evaluated using the NOS scale. Meta-analysis was performed using RevMan5.3 software. RESULTS: A total of 10 studies involving 370 patients, containing 6 randomized controlled trials and 4 cohort studies, were included. The overall quality of the studies was high. Results of the meta-analysis showed that (1) the ASIA sensory function score (MD=5.20, 95%CI:3.50-6.90, P < 0.000 01), the improvement rate of AIS grading (RR=2.26, 95%CI:1.40-3.65, P=0.000 8), and the Barthel index (MD=5.12, 95%CI:1.04-9.20, P=0.01) were higher in the human umbilical cord mesenchymal stem cell treatment group than those in the control group. (2) Compared with the control group, there was no significant difference in ASIA motor function score (MD=3.48, 95%CI:-0.14-7.10, P=0.06), ASIA pinprick sensation score (MD=7.58, 95%CI:-0.44-15.59, P=0.06) and ASIA light touch score (MD=7.67, 95%CI:-0.42-15.77, P=0.06) in the human umbilical cord mesenchymal stem cell treatment group. (3) Sensitivity analysis showed that the ASIA motor function score was higher in the human umbilical cord mesenchymal stem cell treatment group than that in the control group (MD=6.14, 95%CI:4.46-7.81, P < 0.000 01), and the results remained consistent with the previous one for the activities of daily living. In the 10 included articles, no serious adverse reactions were reported, but minor adverse reactions did exist and disappeared after symptomatic treatment. CONCLUSION: The available clinical evidence shows that human umbilical cord mesenchymal stem cells are safe and effective in the treatment of spinal cord injury, with significant improvement in patients’ sensory and motor functions as well as their activity of daily living. Figures and Tables | References | Related Articles | Metrics