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09 July 2021, Volume 25 Issue 19 Previous Issue    Next Issue

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Platelet-derived growth factor-BB induces the differentiation of rat bone marrow mesenchymal stem cells into osteoblasts Wei Qin, Zhang Xue, Ma Lei, Li Zhiqiang, Shou Xi, Duan Mingjun, Wu Shuo, Jia Qiyu, Ma Chuang 2021, 25 (19):  2953-2957.  doi: 10.3969/j.issn.2095-4344.2200 Abstract ( 412 )   PDF (1549KB) ( 38 )   Save BACKGROUND: It has been shown that platelet-derived growth factor-BB secreted by mouse osteoclasts can promote the formation of osteoblasts and vascular cells. Whether platelet-derived growth factor-BB can promote the differentiation of bone marrow mesenchymal stem cells into osteoblasts has not been studied. OBJECTIVE: To investigate the feasibility of platelet-derived growth factor-BB on inducing bone marrow mesenchymal stem cells of rats into osteoblasts.  METHODS:  (1) The bone marrow mesenchymal stem cells of Sprague-Dawley rats were isolated and cultured in vitro. The surface markers CD45, CD29 and CD34 of the third generation were identified by flow cytometry. Bone marrow mesenchymal stem cells with high purity were selected for platelet-derived growth factor-BB intervention experiments. (2) Bone marrow mesenchymal stem cells at passage 3 were induced by 25 μg/L platelet-derived growth factor-BB for 3 days. Cellular immunofluorescence was used to identify type I collagen, followed by alkaline phosphatase modified calcium-cobalt method and azo coupling method kit, alizarin red method. The surface characteristics of osteoblasts were identified. Finally, RT-PCR was used to detect the mRNA levels of Runx-2 and Gli-2 genes.   RESULTS AND CONCLUSION: (1) Cellular immunofluorescence staining showed that the green fluorescence expression rate of type I collagen was more than 90% after induction. (2) Alkaline phosphatase modified calcium-cobalt method demonstrated that black cords were attached to the cytoplasm of the cells, indicating that these cells expressed active alkaline phosphatase. Alkaline phosphatase azo coupling method showed that blue active alkaline phosphatase was found in the cytoplasm of cells. Alizarin red staining exhibited that induced cells gathered together to form small red calcium nodules. (3) RT-PCR showed that the mRNA levels of Gli-2 and Runx-2 genes were higher than those in bone marrow mesenchymal stem cells after platelet-derived growth factor-BB induction (P < 0.05). (4) It is concluded that rat bone marrow mesenchymal stem cells can be differentiated into functional osteoblasts after being induced by platelet-derived growth factor-BB. Figures and Tables | References | Related Articles | Metrics

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Factors affecting the mobilization and collection of autologous peripheral blood hematopoietic stem cells Chen Xiao, Guo Zhi, Chen Lina, Liu Xuanyong, Zhang Yihuizhi, Li Xumian, Wang Yueqiao, Wei Liya, Xie Jing, Lin Li 2021, 25 (19):  2958-2962.  doi: 10.3969/j.issn.2095-4344.3533 Abstract ( 448 )   PDF (1068KB) ( 50 )   Save BACKGROUND: Autologous peripheral blood hematopoietic stem cell transplantation has been widely used in clinic because of its wide age range, fewer complications and low cost. The reconstitution of hematopoietic function after transplantation mainly depends on the quantity and quality of hematopoietic stem cells. Based on the clinical practice, this paper analyzes various factors affecting the collection of peripheral blood hematopoietic stem cells, and calculates the appropriate blood routine standards. It is of great significance to improve the success rate of peripheral blood hematopoietic stem cell collection and autologous transplantation.  OBJECTIVE: To analyze the influence of related factors on the number of CD34+ cells during the mobilization and collection of peripheral blood hematopoietic stem cells of patients with hematological tumors.  METHODS: A retrospective analysis of the effects of various factors on the number of CD34+ cells collected during the mobilization and collection of peripheral blood hematopoietic stem cells of 36 patients in Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences was performed from June 2018 to June 2020, including age, gender, body surface area, disease type, various cell levels on the day of collection, number of chemotherapy before collection, and disease before collection factors such as status, presence or absence of bone marrow involvement at the first diagnosis.    RESULTS AND CONCLUSION: (1) The number of CD34+ cells was related to the number of leukocytes, the absolute value of monocytes, the proportion of monocytes, and the proportion of lymphocytes on the day of collection, and the difference was statistically significant (all P < 0.05). Further analysis of the above four indicators found that the absolute value of monocytes on the day of collection had the highest predictive value for the number of CD34+ cells, followed by the proportion of lymphocytes, leukocytes, and monocytes. (2) Single factor analysis found that age, disease type, mobilization plan, the number of chemotherapy before collection and the presence or absence of bone marrow invasion at the initial diagnosis had no effect on the final collection success rate, and the difference was not statistically significant (all P > 0.05), while gender, disease status before mobilization, body surface area and the final collection success rate were related, and the differences were all statistically significant (all P < 0.05). (3) Results concluded that after mobilization, the blood routine monitoring is used to determine the collection time of peripheral blood hematopoietic stem cells, which mainly monitor the number of leukocytes, the absolute value of monocytes, the proportion of monocytes, and the proportion of lymphocytes. The absolute value of monocytes is the highest predictive value. The cutoff is 1.345×109/L. When the subject is male, pre-collection disease state is complete remission or partial remission, and body surface area is large, the final collection success rate is high. Figures and Tables | References | Related Articles | Metrics

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Simvastatin stimulates osteogenic differentiation of bone marrow mesenchymal stem cells Guo Zhibin, Wu Chunfang, Liu Zihong, Zhang Yuying, Chi Bojing, Wang Bao, Ma Chao, Zhang Guobin, Tian Faming 2021, 25 (19):  2963-2968.  doi: 10.3969/j.issn.2095-4344.3531 Abstract ( 423 )   PDF (2599KB) ( 44 )   Save BACKGROUND: Simvastatin can remarkably stimulate the osteogenic differentiation of bone marrow mesenchymal stem cells, but the mechanism is unknown. Recent studies have confirmed that p38 mitogen-activated protein kinase (MAPK) signaling pathway is involved in regulating the differentiation of bone marrow mesenchymal stem cells into osteoblasts.  OBJECTIVE: To observe the role of p38 MAPK signaling pathway in simvastatin stimulated osteogenic differentiation of bone marrow mesenchymal stem cells.  METHODS: Bone marrow mesenchymal stem cells from the femur and tibia of Sprague-Dawley rats were cultured in vitro, and the second generation of bone marrow mesenchymal stem cells was divided into three groups: control group, simvastatin group (10-7 mol/L simvastatin), and blocking agent group (10 µmol/L p38MAPK signaling pathway specific blocker SB203580 30 minutes before adding simvastatin). Osteogenic differentiation was induced in DMEM complete medium containing 10 mmol/L β-glycerophosphate and 50 mg/L ascorbic acid. Alkaline phosphatase staining was performed at 6 days after intervention in each group. The expressions of p38 MAPK and phosphorylated p38 MAPK were detected by western blot assay at 6 and 12 days. The expression of osteocalcin and collagen type I was detected by immunofluorescence and real-time fluorescent quantitative polymerase chain reaction at 12 days. The formation of calcium nodules was observed by alizarin red staining at 21 days.  RESULTS AND CONCLUSION: (1) Alkaline phosphatase expression and matrix mineralization ability were significantly higher in the simvastatin group than those of control group, and significantly lower in the blocker group than those in the simvastatin group (P < 0.05). (2) The ratio of p38 MAPK in simvastatin group was significantly higher than that in control group (P < 0.05), and that in blocker group was significantly lower than that in simvastatin group (P < 0.05). (3) Simvastatin could promote the expression levels of osteocalcin and collagen type I, while above expression levels in the blocker group were significantly lower than those in the simvastatin group (P < 0.05). (4) It is concluded that simvastatin could promote the differentiation of bone marrow mesenchymal stem cells into osteoblasts, which may be related to stimulate the phosphorylation of p38 MAPK, thereby enhancing the activity of this pathway.  Figures and Tables | References | Related Articles | Metrics

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Knee injury repair using human adipose-derived mesenchymal stem cells-based scaffold-free three-dimensional gel-like construct in pigs Zhang Jianhui, Ma Heran, Tan Yi, Wang Zhihui 2021, 25 (19):  2969-2975.  doi: 10.3969/j.issn.2095-4344.3526 Abstract ( 493 )   PDF (3298KB) ( 132 )   Save BACKGROUND: Compared with the traditional treatment methods, mesenchymal stem cells can fundamentally repair the damaged cartilage tissue, showing advantages in the repair of chondral defect. At present, there is no relevant research report on the ability of adipose-derived mesenchymal stem cells (ADMSCs)-based scaffold-free three-dimensional gel-like construct (ADMSCs-3D-GC) repairing chondral defect. OBJECTIVE: To explore the feasibility of treating porcine chondral defect with ADMSCs-3D-GC. METHODS:  Passage 3-5 of ADMSCs were cultured in the petri dish at a concentration of 4×105/cm2, with the MSCBM medium containing 5% serum substitute UltroGRO and 0.2 mmol/L ascorbic acid-2-phosphate. After stationary culture for 14 days, gently blow up the cells and cell matrix to form a three-dimensional adipose-derived mesenchymal stem cell gel. Osteogenesis, lipogenesis, and chondrogenesis were performed to identify the dryness of adipose mesenchymal stem cells in the gel. A cartilage lesion of 5 mm in diameter and 2 mm in depth was observed on the cartilage of the medial condyle of the femur in each knee of ten 4-month-old female Bama miniature pigs. The ADMSCs-3D-GC transplantation was performed at the damaged site of cartilage of the right knee joint to completely fill the defect and serve as the treatment group. The left side was not treated and served as the control group. After treatment for 4, 6 and 8 months, the cartilage and bone tissues were sampled and stained with hematoxyline and eosin, and Safranine O-Fast Green staining. RESULTS AND CONCLUSION: The ADMSCs-3D-GC had dryness of mesenchymal stem cells, and could promote osteogenesis, lipogenesis and chondrogenesis. Cartilage tissue staining showed that the control group was significantly damaged. In the cell gel treatment group, a group of mature chondrocytes could be seen at the bottom of injury, and gradually transformed into immature chondrocytes, and residual granulation tissues were still visible at the superficial level. The effective rate was 62.5% (5/8) after 6-8 months of treatment. The results showed that ADMSCs-3D-GC could promote the repair of cartilage damage in pig knee joints. Figures and Tables | References | Related Articles | Metrics

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Identification and chondrogenic differentiation of human infrapatellar fat pad derived stem cells Li Congcong, Yao Nan, Huang Dane, Song Min, Peng Sha, Li Anan, Lu Chao, Liu Wengang 2021, 25 (19):  2976-2981.  doi: 10.3969/j.issn.2095-4344.3532 Abstract ( 378 )   PDF (1461KB) ( 58 )   Save BACKGROUND: Human subpatellar fat pad is a kind of waste, which is often removed in total knee arthroplasty. If it is fully utilized, it can be used as a source of mesenchymal stem cells.   OBJECTIVE: To explore the methods of isolation, culture and identification of human infrapatellar fat pad derived stem cells in vitro, to induce chondrogenic differentiation under specific conditions, and to explore the feasibility of being used as seed cells for cartilage tissue engineering. METHODS: The discarded infrapatellar fat pad from eight patients undergoing the total knee arthroplasty was obtained and human infrapatellar fat pad derived stem cells were isolated and cultured according to trypsin digestion, type I collagenase digestion and differential adherence methods. After being cultured to the third generation in vitro, cell morphology observation, cell growth curve and cell surface antigen analysis were performed. In addition, chondrogenic differentiation was induced, and human infrapatellar fat pad derived stem cells were identified by immunohistochemistry, toluidine blue staining and RT-qPCR.   RESULTS AND CONCLUSION: (1) Isolated, purified and cultured human infrapatellar fat pad derived stem cells showed spindle-shaped adherent growth. The growth curve of the third generation of human infrapatellar fat pad derived stem cells was in the shape of “S”. Cells were positive for CD44 and CD105, while negative for CD45. (2) After 14 days of induction, immunohistochemical staining and toluidine blue staining were positive in the differentiation group, and the relative gene expression levels of ACAN, BMP-2, COL2A1 and SOX-9 were significantly higher than those in the blank control group. (3) This study confirmed that mesenchymal stem cells with differentiation potential could be isolated from infrapatellar fat pad, which had strong proliferation ability and chondrogenic differentiation ability in vitro, and were expected to become ideal seed cells for cartilage tissue engineering.  Figures and Tables | References | Related Articles | Metrics

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Adipose-derived stem cells integrated with concentrated growth factors prevent bisphosphonate-related osteonecrosis of the jaws in SD rats Zhang Shengmin, Cao Changhong, Liu Chao 2021, 25 (19):  2982-2987.  doi: 10.3969/j.issn.2095-4344.3529 Abstract ( 322 )   PDF (1268KB) ( 43 )   Save BACKGROUND: Bisphosphonate-related osteonecrosis of jaw may involve invasive dental surgery, infection, jaw injury, immunosuppressive agents and chemotherapeutic drugs, and its potential mechanism and treatment are not clear. Prevention is the main clinical proposition.  OBJECTIVE: To explore the preventive effect of concentrated growth factors integrated with adipose-derived stem cells on bisphosphonate-related osteonecrosis of jaw.  METHODS:  Forty Sprague-Dawley rats were randomly assigned to four groups: control group, zoledronic acid group, concentrated growth factor group, and adipose-derived stem cells combined with concentrated growth factor group (n=10 per group). Except the control group, rats in the other three groups were injected with zoledronic acid (80 μg/kg) through the tail vein once a week for 12 consecutive weeks to establish a bisphosphonate-related osteonecrosis of jaw model. Rats in the control group were injected with 0.1 mL of saline through the tail vein. The right mandibular first molar was extracted at the 8th week. In the concentrated growth factor group, 0.5 cm × 0.5 cm concentrated growth factors were implanted immediately after tooth extraction. In the adipose-derived stem cells combined with concentrated growth factor group, 0.5 cm × 0.5 cm concentrated growth factor/adipose-derived stem cell complex was implanted into the extraction socket immediately after tooth extraction. The control group and zoledronic acid group were not treated after tooth extraction. The rats were killed 8 weeks after extraction. The gingival regeneration and bone tissue regeneration around the extraction wound were detected by observation of tooth extraction wound, Micro-CT and hematoxylin-eosin staining.  RESULTS AND CONCLUSION: Compared with other three groups, concentrated growth factor/adipose-derived stem cell complex significantly promoted the healing of soft tissue and new bone formation around tooth extraction, reduced the dead bone formation, and effectively prevented the occurrence of bisphosphonate-related osteonecrosis of jaw.  Figures and Tables | References | Related Articles | Metrics

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Comparison of biological characteristics of adipose derived mesenchymal stem cells in Wuzhishan inbreed miniature pigs aged two different months Gao Yuanhui, Xiang Yang, Cao Hui, Wang Shunlan, Zheng Linlin, He Haowei, Zhang Yingai, Zhang Shufang, Huang Denggao 2021, 25 (19):  2988-2993.  doi: 10.3969/j.issn.2095-4344.3522 Abstract ( 413 )   PDF (3002KB) ( 36 )   Save BACKGROUND: Stem cells have been the focus of regenerative medicine research. Many factors affect the biological characteristics of stem cells, among which donor age is one of the critical factors. OBJECTIVE: To observe biological characteristics of two types of inbreed line miniature pigs of Wuzhishan adipose-derived mesenchymal stem cells so as to screen the optimal seed cell source. METHODS:  Inbreed line miniature pigs of Wuzhishan adipose-derived mesenchymal stem cells aged 4 and 12 months were selected as materials. The passage 3 and passage 10 of cells were selected to observe their cell morphology, draw cell proliferation curve, and detect cell surface antigen, cell cycle and apoptosis. Afterwards, osteogenic differentiation was performed with Alizarin red staining, followed by adipogenic differentiation with Oil Red O staining and cell senescence β-galactosidase staining. RESULTS AND CONCLUSION: (1) The morphology of cells at 4 and 12 months both showed vortex-shaped adherent growth. The expression of surface markers CD29, CD44 and CD90 was positive, while that of CD8a, CD45 and HLA-DR was negative. (2) The proliferation of cells at 4 and 12 months was stronger in passage 3. In passage 10, the percentage of cells in the G0/G1 phase (P < 0.001) and early apoptosis (P < 0.001) increased, while in the S and G2/M phases, it decreased at 12 months compared with 4 months (P < 0.001). (3) There was no significant difference in the differentiation ability of cells at passage 3 in vitro between 4 and 12 months. The calcification nodule rate and lipid droplet rate of cells at 12 months of passage 10 were significantly lower than at 4 months of passage 10 (P < 0.001). (4) The β-galactosidase of cells was almost not expressed at 4 and 12 months of passage 3. However, in the passage 10, the positive rate of cells at 12 months was significantly higher than that at 4 months (P < 0.001); and the cell morphology became more flattened, hypertrophic and less refractive. (5) It is concluded that adipose-derived mesenchymal stem cells of inbreed line miniature pigs of Wuzhishan at 4 months showed stronger proliferation and differentiation ability, while showed lower senescence on β-galactosidase activity, suggesting that 4-month cells are more suitable for autograft.  Figures and Tables | References | Related Articles | Metrics

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Mechanism by which exosomes from human fetal placental mesenchymal stem cells protect lung epithelial cells against oxidative stress injury Yan Xiurui, Tao Jin, Liang Xueyun 2021, 25 (19):  2994-2999.  doi: 10.3969/j.issn.2095-4344.3537 Abstract ( 354 )   PDF (1172KB) ( 85 )   Save BACKGROUND: Previous studies have confirmed that the culture supernatant of human fetal placental mesenchymal stem cells can protect lung epithelial cells from oxidative damage by inhibiting apoptosis. OBJECTIVE: To investigate the protective effect of exosomes derived from human fetal placental mesenchymal stem cells on oxidative stress injured lung epithelial cells BEAS-2B.  METHODS:  BEAS-2B cells were cultured in vitro with DME/F-12 complete medium containing different concentrations (100, 200, 300, 400, and 500 μmol/L) of H2O2 for 4 hours. Cells were cultured with DME/F-12 complete medium containing 300 μmol/L H2O2 for 2, 4, and 6 hours. Cell viability was measured by CCK-8 assay to determine the conditions of oxidative damaged model. Hoechst33258 staining was used to observe apoptosis. Q-PCR and western blot assay were used to detect the gene and protein expression of bax and bcl-2 to determine the validity of the model. The culture supernatant of human fetal placental mesenchymal stem cells from P3 was collected and the exosomes were isolated in accordance with exosome extraction kit instructions. The exosomes were treated on oxidative damaged BEAS-2B cells, and the expression levels of bax, bcl-2, nrf2 and keap1 were identified by q-PCR and western blot assay.   RESULTS AND CONCLUSION: (1) When BEAS-2B cells were treated with 300 μmol/L H2O2 for 4 hours, and the cell viability was (51.96±2.17)%, which could be used as the optimum condition for oxidative damaged model. Hoechst33258 staining, q-PCR and western blot assay showed that the model was effective. (2) Compared with the injury group, the expression of bax significantly decreased and the expression of bcl-2 significantly increased in exosomes group; the expression of nrf2 significantly increased and the expression of keap1 significantly decreased in exosomes, with significant differences (P < 0.05). (3) The results indicate that the exosomes derived from human fetal placental mesenchymal stem cells can inhibit the apoptosis of BEAS-2B cells induced by oxidative damage, and its mechanism may be related to the activation of Nrf2-Keap1-ARE signaling pathway.   Figures and Tables | References | Related Articles | Metrics

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Isolation and culture of rabbit aortic endothelial cells and biological characteristics Cao Yang, Zhang Junping, Peng Li, Ding Yi, Li Guanghui 2021, 25 (19):  3000-3003.  doi: 10.3969/j.issn.2095-4344.3525 Abstract ( 335 )   PDF (1333KB) ( 39 )   Save BACKGROUND: To obtain a large number of high-purity endothelial cells, so as to carry out better experimental research on endothelial cell-related diseases, this paper updated the separation and culture methods of endothelial cells by improving the ratio of digestive enzymes. OBJECTIVE: To explore the culture method of rabbit aortic endothelial cells in vitro and identify them, so as to lay a foundation for better experimental study of endothelial cell-related diseases. METHODS: The endothelial tissue and cell suspension of rabbit aorta were obtained by compound enzyme digestion. After density gradient centrifugation, high-purity vascular endothelial cells were obtained and cultured in vitro. Furthermore, the rabbit aortic endothelial cells were identified by CD34 immunocytochemical staining and the cell purity was analyzed. RESULTS AND CONCLUSION: (1) The vascular endothelial cells cultured in vitro were arranged in the shape of typical “paving stone”. (2) In addition, immunohistochemistry showed that the isolated cells were strongly positive for CD34-staining, to prove that they were endothelial cells. (3) The quantitative analysis of the immunohistochemical photos showed that all the cells were CD34-positive cells; that is, the purity of the obtained endothelial cells was more than 95%. (4) The endothelial tissue and cell suspension of rabbit aorta were obtained by compound enzyme digestion. After density gradient centrifugation, high-purity vascular endothelial cells were obtained. Rabbit aortic endothelial cells were isolated and cultured successfully in vitro.  Figures and Tables | References | Related Articles | Metrics

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Biological characteristics of hypoxic preconditioned human amniotic mesenchymal stem cells Dai Min, Wang Shuai, Zhang Nini, Huang Guilin, Yu Limei, Hu Xiaohua, Yi Jie, Yao Li, Zhang Ligang 2021, 25 (19):  3004-3008.  doi: 10.3969/j.issn.2095-4344.3527 Abstract ( 468 )   PDF (2112KB) ( 34 )   Save BACKGROUND: Stem cell transplantation has brought hope for many difficult diseases, but the survival number of transplanted cells is small and the secretion function is poor, so it is difficult to play a therapeutic effect, which hinders the clinical application of stem cell transplantation. Hypoxic preconditioning can  effectively improve the biological characteristics of implanted cells, such as proliferation activity, anti-apoptotic ability and secretion function. Therefore, human amniotic mesenchymal stem cells pretreated with hypoxia may play a better therapeutic role in tissue damage repair. OBJECTIVE: To study the effects of hypoxic preconditioning on the biological characteristics of human amniotic mesenchymal stem cells.  METHODS: The mechanical method and enzymatic digestion were used to separate human amniotic mesenchymal stem cells, and then cultured it up to the third generation. After having hypoxic pretreatment (3% O2) for 48 hours, the nomoxic (21% O2) control group was set. The proliferation activity and DNA synthesis rate of human amniotic mesenchymal stem cells  in the two groups were detected by CCK-8 and Edu proliferation experiments. The two groups of cells were cultured by serum-free medium for 24 hours. Apoptosis was detected using Annexin V-FITC/PI assay. The supernatant was collected. The levels of angiogenic factors secreted in the supernatant were detected by using the Proteome Profiler.  RESULTS AND CONCLUSION: Hypoxic preconditioning does not affect the characteristics of human amniotic mesenchymal stem cells, but can improve the proliferation activity of human amniotic mesenchymal stem cells; in serum-free culture conditions, hypoxic preconditioning can enhance the anti-apoptotic effect of human amniotic mesenchymal stem cells, and secrete more angiogenic factors. Figures and Tables | References | Related Articles | Metrics

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Radial extracorporeal shock wave therapy regulates the proliferation and differentiation of neural stem cells in the hippocampus via Notch1/Hes1 pathway after cerebral ischemia Su Mingzhu, Ma Yuewen 2021, 25 (19):  3009-3015.  doi: 10.3969/j.issn.2095-4344.3538 Abstract ( 320 )   PDF (1849KB) ( 47 )   Save BACKGROUND: Our previous research found that radial extracorporeal shock wave therapy can promote the proliferation and differentiation of neural stem cells in vitro, and the specific mechanism is related to the upregulation of Notch1 signaling pathway. However, there is no relevant research report on whether the proliferation and differentiation of neural stem cells can also be promoted through this pathway in vivo. OBJECTIVE: To explore whether radial extracorporeal shock wave therapy can promote the proliferation and differentiation of neural stem cells in hippocampus after cerebral ischemia through Notch1/Hes1 signaling pathway in vivo.  METHODS:  Rat models of right cerebral ischemia were established by middle cerebral artery occlusion. After successful modeling, the rats were randomly divided into two groups: the radial extracorporeal shock wave therapy group (treatment group) and the control group. In the treatment group, 72 hours after middle cerebral artery occlusion, radial extracorporeal shock wave therapy was directly applied to the right side of the rats’ head at a dose of 0.1 MPa, 200 impulses, and 10 Hz, every three days. In the control group, 72 hours after middle cerebral artery occlusion, the same dose of radial extracorporeal shock wave therapy was given, but the transmitter probe did not touch the head of the rats, only the sound stimulation. Both groups were observed at 12, 21 and 30 days after middle cerebral artery occlusion. Expression levels of nestin, NSE, Notch1 and Hes1 in the ischemic hippocampus of rats were detected by immunohistochemistry, western blot assay, and RT-PCR. RESULTS AND CONCLUSION: (1) The mNss score of the treatment group was significantly lower than the control group at 12, 21, and 30 days, which indicated that radial extracorporeal shock wave therapy could significantly improve neurological function in rats with cerebral ischemia. (2) Compared with the control group, the expression of Nestin and NSE in ischemic hippocampus of rats increased significantly in the treatment group, which indicated that radial extracorporeal shock wave therapy could promote the proliferation and differentiation of neural stem cells in hippocampus after cerebral ischemia. (3) Compared with the control group, the expression of Notch1 and Hes1 in the ischemic hippocampus of rats in the treatment group was higher than that in the control group, which suggested that radial extracorporeal shock wave therapy could upregulate the expression of Notch1/Hes1 signaling pathway in the hippocampus. (4) The results confirm that radial extracorporeal shock wave therapy can promote the proliferation and differentiation of neural stem cells in the hippocampus after cerebral ischemia, and improve neurological function. The precise mechanism is related to the upregulation of Notch1/Hes1 signaling pathway.  Figures and Tables | References | Related Articles | Metrics

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Chinese medicine compound preparation inhibits proliferation of CD133+ liver cancer stem cells and the expression of stemness transcription factors Qin Yanchun, Rong Zhen, Jiang Ruiyuan, Fu Bin, Hong Xiaohua, Mo Chunmei 2021, 25 (19):  3016-3023.  doi: 10.3969/j.issn.2095-4344.3523 Abstract ( 260 )   PDF (1504KB) ( 47 )   Save BACKGROUND: The malignant transformation of cancer originating from stem cells is increasingly recognized. Liver cancer stem cells have the potential of continuous self-renewal and multi-directional differentiation, which can promote the occurrence and development of liver cancer, postoperative recurrence and the production of drug resistance. OBJECTIVE: To explore the effect of Fuhe preparation formula on proliferation of CD133+ liver cancer stem cells and stemness transcription factor expression.  METHODS:  CD133+ HepG2 liver cancer stem cells were selected by immunomagnetic bead method. CD133+ HepG2 cells were treated with serum containing 2%, 4%, 8%, 10%, 12% and 16% Fuhe preparation formula respectively. The inhibitory rate of CD133+ HepG2 cells was determined by CCK-8 method, and the optimal volume fraction of serum containing drugs was selected. The CD133+ HepG2 liver cancer stem cells were divided into dimethyl sulfoxide group, application and preparation group, serum control group and blank control group. Cells in the dimethyl sulfoxide group were intervened with 0.05% dimethyl sulfoxide. Cells in the application and preparation group were intervened with 16% application and preparation containing serum. Cells in the serum control group were intervened with 16% normal rat serum. After 6 days of intervention, the percentage of CD133+ HepG2 liver cancer stem cells was detected by flow cytometry. The mRNA and protein levels of transcription factors SOX2, NANOG, and OCT4 were detected by RT-PCR and western blot assay.  RESULTS AND CONCLUSION: (1) The serum containing application and preparation formula inhibited the proliferation of CD133+ HepG2 cells, which was related to the time and concentration. The inhibitory effect of 16% application and preparation formula was the most obvious in 72 hours (P < 0.05). (2) Compared with the serum control and blank control groups, the percentage of CD133+ HepG2 liver cancer stem cells was decreased in the application and preparation and dimethyl sulfoxide groups (P < 0.05), and the effect was more obvious in the application and preparation group. (3) Compared with the serum control and blank control groups, SOX2, NANOG, OCT4 mRNA and protein expression levels were downregulated in the application and preparation and dimethyl sulfoxide groups (P < 0.05), and the effect was more obvious in the application and preparation group. (4) These findings conclude that the serum containing application and preparation formula can effectively reduce the expression levels of CD133, a marker on the surface of liver cancer stem cells, and transcription factors SOX2, NANOG and OCT4, and can reduce the malignant degree of liver cancer stem cells.  Figures and Tables | References | Related Articles | Metrics

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Construction of miR-146b overexpression lentiviral vector and the effect on the proliferation of hippocampal neural stem cells Dai Yaling, Chen Lewen, He Xiaojun, Lin Huawei, Jia Weiwei, Chen Lidian, Tao Jing, Liu Weilin 2021, 25 (19):  3024-3030.  doi: 10.3969/j.issn.2095-4344.3539 Abstract ( 321 )   PDF (2611KB) ( 48 )   Save BACKGROUND: More and more studies have confirmed that miR-146b plays an important role in the nervous system, which provides a new therapeutic direction for treatment of nervous system diseases. OBJECTIVE: To construct rat miR-146b overexpression lentiviral vector and observe the effect of miR-146b overexpression on the proliferation of primary hippocampal neural stem cells.  METHODS:  (1) PCR extended to obtain the full-length sequence of rat miR-146b, which was ligated into the lentiviral vector pLVX-Luciferase-Puro. After double digestion and DNA sequencing identification, lentivirus was packed in 293T cells and virus supernatant was collected. (2) Primary hippocampal neural stem cells of newborn SD rats were isolated and cultured, and pLVX-Luciferase-rno-miR-146b-Puro lentivirus was transfected into hippocampal neural stem cells. After 24 and 48 hours of transfection, RT-PCR was applied to detect the expression level of miR-146b, while the expression of Nestin was observed by immunofluorescence staining. MTS method and Edu method were used to measure cell proliferation. After 48 hours of transfection, cell cycle was detected by flow cytometry.   RESULTS AND CONCLUSION: (1) The results of sequencing identification showed that rat miR-146b was successfully cloned into pLVX-Luciferase-Puro overexpression vector. (2) After 24 and 48 hours of transfection, expression level of miR-146b in hippocampal neural stem cells increased significantly. (3) The number of Nestin immunofluorescence-positive cells was significantly reduced after miR-146 overexpression, and the proliferation ratio was decreased, and the cell cycle mainly remained in G1 phase. (4) The results confirm that the rat miR-146b overexpression lentivirus vector was successfully packaged and it could inhibit the proliferation of primary hippocampal neural stem cells after transfection, but the mechanism of its regulation of target genes needs further study.  Figures and Tables | References | Related Articles | Metrics

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Mesenchymal stem cells for treatment of intervertebral disc degeneration: a bibliometric and visualization analysis based on Web of Science database Zhang Kai, Zhang Xiaobo, Shi Jintao, Wang Keping, Zhou Haiyu 2021, 25 (19):  3031-3038.  doi: 10.3969/j.issn.2095-4344.3535 Abstract ( 329 )   PDF (2545KB) ( 157 )   Save BACKGROUND: Mesenchymal stem cells have the characteristics of self-renewal and multi-directional differentiation, and have great potential and application prospects in the treatment of intervertebral disc diseases.  OBJECTIVE: To analyze the literature of mesenchymal stem cells in the treatment of intervertebral disc degenerative diseases using bibliometric analysis, and to understand the research trends and hotspots  in this field, and to provide basis and suggestions for its follow-up development. METHODS:  With the theme of mesenchymal stem cell therapy for intervertebral disc degeneration, we searched the relevant literature included in the Web of Science database from 2000 to 2019, analyzed the annual number of paper published, and scientific research funding. Citespace5.5.R2 software was used to analyze the cooperation relationship of authors, countries and research institutions, the co-citation of journals or literatures. Finally, cluster analysis, burst analysis and time zone graph analysis were performed on keywords.   RESULTS AND CONCLUSION: (1) A total of 648 papers were included, with journal articles as the main type of literature. (2) Most of the funding were sponsored by China and USA (more than 50%). (3) A total of 206 authors were included, out of whom 70 authors published more than 3 papers, and the principal researchers were Daisuke Sakai (Japan) focusing on mesenchymal stem cells transplantation for intervertebral disc degeneration, Judith A Hoyland (Great Britain) focusing on regulation of myeloid cell phenotype by mesenchymal stem cells, and Makarand V Risbud (US) focusing on induction of mesenchymal stem cell differentiation. (4) 125 countries and institutions were included: China and USA were the two main countries. (5) 154 journals were included, as SPINE was the journal with the most published articles. (6) The keyword analysis showed that the research in this field can be divided into three phases: phase 1 from 2005 to 2012, mainly investigating gene expression differences, chondrogenic differentiation of mesenchymal stem cells, and extracellular matrix changes in the intervertebral disc; phase 2 from 2012 to 2017, mainly investigating mesenchymal stem cell injection therapy and changes in the microenvironment of the intervertebral disc; phase 3 from 2017 to 2019, the main study is cell therapy and disc regeneration promoted by mesenchymal stem cells. (7) The probably research direction was to extract mesenchymal stem cells and induce their differentiation to nucleus pulposus, paracrine secretion of mesenchymal stem cells on the function of disc cells and mesenchymal stem cells combined with tissue engineering technology to promote intervertebral disc regeneration.  Figures and Tables | References | Related Articles | Metrics

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Problems and challenges in regeneration and repair of spinal cord injury Tian Ting, Li Xiaoguang 2021, 25 (19):  3039-3048.  doi: 10.3969/j.issn.2095-4344.2198 Abstract ( 501 )   PDF (1419KB) ( 106 )   Save BACKGROUND: Spinal cord injury leads to severe sensory and motor dysfunctions, abnormal reflexes, and autonomic nerve disorders. At present, there are no effective clinical therapies for spinal cord injury. In recent years, researchers have developed a variety of novel approaches, opening up new avenues for clinical treatment of spinal cord injury. OBJECTIVE: To characterize the pathophysiological process of spinal cord injury, summarize recent advances in regeneration and repair of spinal cord injury, analyze the current status and challenges with respect to clinical translation, and consider the future development trend for treatment of spinal cord injury. METHODS: The relevant articles were searched in PubMed database from 2003 to 2020 using the key words of “spinal cord injury, neuroplasticity, functional recovery, therapeutic strategy, combinatory therapies, clinical translation”. 398 articles were initially retrieved. After sorting and screening, 116 articles were eventually included for analysis and summary.  RESULTS AND CONCLUSION: The pathophysiology of spinal cord injury involves primary injury and secondary injury. Targeting the pathophysiology of spinal cord injury, the potential therapeutic strategies for spinal cord injury include (1) enhance neuroprotection: reduction of secondary injury; (2) promote regenerative repair: activate the intrinsic regenerative capacity of neurons, ameliorate microenvironment, cell transplantation, neuromodulation and rehabilitation, brain-machine interface, and combinatory therapies. The pathological process of spinal cord injury is very complicated, and individual treatment is insufficient to promote nerve regeneration and functional recovery after spinal cord injury in humans. Combinatory strategies have demonstrated greater beneficial outcomes than individual treatment by addressing multiple aspects of spinal cord injury pathology. Clinical trials in the future should strengthen multidisciplinary conversation and cooperation, to determine the optimal combinatory approaches, promoting functional recovery of patients with spinal cord injury. Figures and Tables | References | Related Articles | Metrics

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Effectiveness and clinical application limitations of stem cells in the treatment of multiple sclerosis and optic neuromyelitis spectrum diseases Zhang Hongqing, Xie Xufang, Wu Xiaomu 2021, 25 (19):  3049-3056.  doi: 10.3969/j.issn.2095-4344.3501 Abstract ( 645 )   PDF (708KB) ( 65 )   Save BACKGROUND: The self-renewal and differentiation potential of stem cells make it a research hotspot in the medical field. Its immune regulation and neuroprotective effects make stem cells applications in multiple sclerosis and optic neuromyelitis spectrum diseases favored by clinicians. OBJECTIVE: To summarize the research progress of stem cells in multiple sclerosis and optic neuromyelitis spectrum diseases in recent years. METHODS: The PubMed and Web of Science databases were searched for documents related to stem cell therapy for multiple sclerosis and optic neuromyelitis spectrum diseases published in recent years. Search terms are “stem cells, multiple sclerosis, MS, EAE, neuromyelitis optica spectrum diseases, neuromyelitis optica, NMO, NMODS”. According to inclusion and exclusion criteria, 75 related articles were included for careful reading and comprehensive analysis.  RESULTS AND CONCLUSION: Compared with past immunosuppressive therapies, stem cell transplantation has great potential for the treatment of multiple sclerosis and optic neuromyelitis spectrum diseases. However, cell selection, donor source, transplantation time, route, post-transplantation long-term safety and effectiveness limit clinical applications.  Figures and Tables | References | Related Articles | Metrics

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Stem cells, cytokines, hormones, neuropeptides and genes in traumatic brain trauma to promote fracture healing Li Xiangze, Bu Xianmin, Li Dongmei, Chi Yulei, Su Qiang, Jin Xintong, Zhao Jian, Zhang Gaotian, Wu Bin, Meng Chunyang 2021, 25 (19):  3057-3063.  doi: 10.3969/j.issn.2095-4344.2199 Abstract ( 454 )   PDF (726KB) ( 231 )   Save BACKGROUND: Delayed fracture healing and nonunion are common complications in clinic. The mechanism of brain injury promoting fracture healing is the focus of current research.   OBJECTIVE: To summarize the latest research progress on the mechanism of promoting fracture healing by traumatic brain injury, and provide theoretical basis for clinical application.  METHODS: The first author searched CNKI, Wanfang, VIP, PubMed, Embase and Web of Science databases from January 2009 to March 2020. Search terms were “traumatic brain injury, fracture healing, bone marrow mesenchymal stem cells, fat stem cells, cytokines, hormones, neuropeptides, genes” in Chinese and English. Totally, 63 articles that met the inclusion criteria were selected.  RESULTS AND CONCLUSION: Fracture healing is a complex and orderly pathological process, involving a variety of pathophysiological mechanisms and many factors affect bone regeneration. Large numbers of clinical studies have shown that traumatic brain injury can promote healing of fracture, but there is no systematic conclusion on the specific mechanism of fracture repair. Moreover, the current research is aimed at detection of the role of one or several factors alone. There are gaps in systematic research and dynamic detection of all relevant factors. Therefore, in the future clinical research, we should observe the expression of related factors at different time points during post-traumatic bone regeneration, and further explore the action mechanism of their interaction, so as to provide sufficient theoretical basis for clinical fracture nonunion, delayed fracture healing, heterotopic ossification and guide clinical treatment. Figures and Tables | References | Related Articles | Metrics

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Bone morphogenetic protein 9 regulates stem cell differentiation and bone regeneration Wang Liu, Song Dongzhe, Huang Dingming 2021, 25 (19):  3064-3070.  doi: 10.3969/j.issn.2095-4344.3515 Abstract ( 475 )   PDF (1691KB) ( 47 )   Save BACKGROUND: Bone morphogenetic protein 9 (BMP9) possesses the potential to regulate the osteogenic differentiation of stem cells. A large number of studies have shown that BMP9 can promote the repair of bone defects in animals. OBJECTIVE: To explore the mechanism of BMP9 regulating stem cell differentiation, to discuss the potential factors affecting the promotion of stem cell osteogenic differentiation by BMP9, and to explore the application perspective of BMP9 in bone tissue engineering.  METHODS: In PubMed, Web of Science, Wanfang, Weipu and CNKI, the authors searched the relevant literature from 1990 to 2020 with the keywords “bone morphogenetic protein 9/BMP9, mesenchymal stem cell, stem cell, bone regeneration, bone reconstruction”. According to the inclusion and exclusion criteria, the repetitive, unrelated, or low-quality articles were excluded. Finally, 67 articles were summarized and analyzed. RESULTS AND CONCLUSION: As a key molecule of bone morphogenetic protein family, BMP9 has a strong ability to promote stem cell differentiation and bone tissue regeneration. BMP9 regulates stem cell differentiation mainly through BMP9-SMAD signal pathway and BMP9-MAPK signal pathway. TGFβ, Wnt/β-catenin and Notch signaling pathways can regulate the expression of key molecules in BMP9 signaling pathway to indirectly affect the osteogenic differentiation of BMP9. In oral and maxillofacial bone tissue engineering and osteoarticular disease model, BMP9 can significantly promote bone tissue regeneration, bone defect repair and bone tissue reconstruction. However, with the limitations of the existing research, the specific mechanism of BMP9 regulating stem cell differentiation and bone tissue regeneration remains to be further explored, and the toxic and side effects of stimulating BMP9 on other tissues and organs still need to be evaluated.  Figures and Tables | References | Related Articles | Metrics

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Application prospects and problems of peripheral blood derived mesenchymal stem cells in cartilage repair of osteoarthritis Yang Tengyun, Li Yanlin, Liu Dejian, Wang Guoliang 2021, 25 (19):  3071-3076.  doi: 10.3969/j.issn.2095-4344.3520 Abstract ( 668 )   PDF (613KB) ( 146 )   Save BACKGROUND: With the application of tissue engineering technology to the cartilage repair research field in recent years, mesenchymal stem cells as a kind of adult stem cells with the characteristics of self-renewal, strong proliferation ability, clonal cell population and multidirectional differentiation, are ideal seed cells for cartilage repair. Moreover, peripheral blood derived mesenchymal stem cells, due to its conveniently, minimally invasive to the patient, have become the research focus in the field. OBJECTIVE: To review research status of peripheral blood derived mesenchymal stem cells and their applications in cartilage repair of osteoarthritis, to analyze the main problems of limited clinical application and possible solutions, so as to rationally utilize peripheral blood derived mesenchymal stem cells and find suitable seed cells for the treatment of cartilage injury. METHODS: Relevant articles collected from PubMed database, Wanfang database and CNKI Chinese journal full-text database were searched. The key words were “peripheral blood derived mesenchymal stem cells, circulating mesenchymal stem cells, cartilage repair, osteoarthritis treatment” in English, and “peripheral blood derived mesenchymal stem cells, circulating mesenchymal stem cells, cartilage repair, osteoarthritis” in Chinese. Finally, 57 articles were included for summary. RESULTS AND CONCLUSION: The recent research on cartilage tissue engineering has increased significantly and continuously in recent years. Peripheral blood derived mesenchymal stem cells have the advantage of chondrogenesis, can be used as more ideal seed cells in cartilage tissue engineering and have a good clinical application prospect. Figures and Tables | References | Related Articles | Metrics

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Application and effect of induced pluripotent stem cells in bone surgery tissue engineering Xia Guoming, Xu Qiang, Liu Xuqiang, Yu Xiaolong, Dai Min 2021, 25 (19):  3077-3082.  doi: 10.3969/j.issn.2095-4344.3503 Abstract ( 395 )   PDF (600KB) ( 75 )   Save BACKGROUND: Induced pluripotent stem cells have many advantages such as differentiation totipotency, wide source, easy access and no ethical constraints, so they rapidly become promising seed cells in the field of tissue engineering. OBJECTIVE: To review the progress of induced pluripotent stem cells in bone surgery tissue engineering.  METHODS: The electronic database PubMed was searched by the first author. The key words were “iPSCs, osteanagenesis, tendon, spinal cord, spinal cord, tissue engineering, regenarative medicine”. The literature published from 2000 to 2020 was searched. A total of 50 articles were selected as references for review, screening the documents with strong relevance and excluding those with little content.  RESULTS AND CONCLUSION: Compared with mesenchymal stem cells and embryonic stem cells, induced pluripotent stem cells have many advantages, such as wide source, easy access, no ethical constraints and controllable gene instability, reducing immune rejection. Induced pluripotent stem cells technology in bone surgery tissue engineering research showed satisfactory results. Figures and Tables | References | Related Articles | Metrics

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Effect of stem cell derived exosomes on repairing peripheral nerve injury Wang Kang, Zhi Xiaodong, Wang Wei 2021, 25 (19):  3083-3089.  doi: 10.3969/j.issn.2095-4344.3528 Abstract ( 462 )   PDF (1167KB) ( 107 )   Save BACKGROUND: Stem cell-derived exosomes carry biologically active substances such as miRNAs and proteins that contribute to intercellular signal transduction, which have an important and positive impact on the nerve repair. They have a therapeutic effect similar to stem cell transplantation and can be used to replace stem cell transplantation for treating peripheral nerve injury.  OBJECTIVE: To summarize the application of exosomes from stem cells in the treatment of peripheral nerve injury, so as to provide reference and basis for exosomes applied in the treatment of peripheral nerve injury. METHODS: Articles in PubMed database from 2000 to 2020 were searched using the search terms of “peripheral nerve, injury, damage, stem cells, embryonic stem cells, induced pluripotent stem cells, mesenchymal stem cells, exosomes, repair, regenerate.” Articles in databases of CNKI, VIP and WANFANG from 2000 to 2020 were retrieved with the search terms of “peripheral nerve, injury, damage, stem cells, embryonic stem cells, induced pluripotent stem cells, mesenchymal stem cells, exosomes, repair, regenerate.” The literature and references were reviewed one by one.  RESULTS AND CONCLUSION: Stem cell-derived exosomes exert powerful tissue repair, regeneration and protection capabilities similar to those of stem cells. Stem cell-derived exosomes are a new strategy for “cell-free” therapy, because they can avoid immune rejection, tumorigenic risks and other problems during treatment with stem cell transplantation and have better capabilities of binding extracellular matrix. However, the application of stem cell-derived exosomes in peripheral nerve research still needs a lot of basic researches to be accumulated, and the combination with tissue engineering and genetic engineering needs further exploration.  Figures and Tables | References | Related Articles | Metrics

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Bladder cancer stem cell markers and related signaling pathways: antibody targeted therapy Chen Jie, Liao Chengcheng, Chen Zhiwei, Wang Yan 2021, 25 (19):  3090-3096.  doi: 10.3969/j.issn.2095-4344.3504 Abstract ( 489 )   PDF (670KB) ( 50 )   Save BACKGROUND:  Bladder cancer is one of the most common malignancies of the urinary system and is a serious threat to patient. The continuous in-depth study of cancer stem cells provides a new therapeutic direction for the cure of bladder cancer, in which important markers and signaling pathways of bladder cancer stem cells provide a strong basis for targeted therapy of bladder cancer.  OBJECTIVE: To review the research progress of major markers and signaling pathways of bladder cancer stem cells. METHODS: A computer-based search for articles published from 2004 to 2020 was performed in CNKI and PubMed databases. The key words were “bladder cancer, cancer stem cells (CSCs)” in Chinese and English. We selected articles related to bladder cancer stem cell markers and signaling pathways, and summarized, sorted and discussed the role of important markers and signaling pathways in the initiation, recurrence, metastasis and drug resistance of bladder cancer. RESULTS AND CONCLUSION: The markers and signaling pathways of bladder cancer stem cells play an important role in the development, progression, invasion, metastasis, and drug resistance of bladder cancer. The further study of them can provide new ideas for the further development of antibody targeted therapy against cancer stem cells.  Figures and Tables | References | Related Articles | Metrics

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Role and mechanism of exosomes derived from mesenchymal stem cells in reproductive system diseases Zhao Shuangdan, Zheng Jiahua, Qi Wenbo, Huang Xianghua 2021, 25 (19):  3097-3102.  doi: 10.3969/j.issn.2095-4344.3521 Abstract ( 592 )   PDF (940KB) ( 89 )   Save BACKGROUND: Mesenchymal stem cells are one of the most commonly used cell types in regenerative medicine. In recent years, exosomes derived from mesenchymal stem cells play an important role in some reproductive diseases and have become a new hot spot of research in the field of reproductive medicine. OBJECTIVE: To review the research progress of exosomes derived from mesenchymal stem cells in premature ovarian failure, polycystic ovary syndrome, intrauterine adhesions and common reproductive system tumors, and discuss the application and research of exosomes derived from mesenchymal stem cells in the future. METHODS: The literature search was performed in PubMed and CNKI databases, and the key words were “mesenchymal stem cells, exosome, premature ovarian insufficiency, premature ovarian failure, polycystic ovary syndrome, intrauterine adhesions, endometrium, Asherman’s syndrome, ovarian cancer, cervical cancer, endometrial carcinoma, embryo” in English and Chinese, respectively. Fifty-six articles were finally reviewed. RESULTS AND CONCLUSION: Exosomes derived from mesenchymal stem cells can not only be used as a therapeutic carrier for some reproductive diseases, but also become an important target for studying the pathogenesis of diseases. Exosome derived from mesenchymal stem cells is expected to become a new “cell-free” therapy for reproductive system diseases. Figures and Tables | References | Related Articles | Metrics

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Mesenchymal stem cell transplantation in the treatment of myocardial infarction: problems, crux and new breakthrough Sun Weixing, Zhao Yongchao, Zhao Ranzun 2021, 25 (19):  3103-3109.  doi: 10.3969/j.issn.2095-4344.3536 Abstract ( 466 )   PDF (716KB) ( 101 )   Save BACKGROUND: Myocardial infarction is a serious threat to human health, and existing curative treatments are limited. The development of stem cell biology and tissue engineering has shed light on the treatment of myocardial infarction. OBJECTIVE: We intended to review the biological characteristics, effectiveness of treatment, number, route, timing and mechanism of action of transplanted cells, and to provide a theoretical reference to promote translation and application of stem cell transplantation in the treatment of myocardial infarction. METHODS: Key words were “mesenchymal stem cells, stem cells, biological characteristics, differentiation, proliferation, immunomodulation, homing, paracrine, miocardial infarction, transplantation, RNA methylation” in English and Chinese. We mainly searched similar reviews published from 2016 to 2020, especially in recent 3 years, through CNKI and PubMed. The repeated and irrelevant literature was removed. Finally, 53 articles were included for review.   RESULTS AND CONCLUSION: Successful advances have been made in the prevention and treatment of myocardial infarction, such as the differentiation into myocardium, immune regulation, homing, and therapeutic mechanism. However, controversies still exists, such as the effectiveness of transplantation therapy, the number of cells required for transplantation, as well as the route and timing, which limited the development of stem cell transplantation. Recently, with the deepening of epigenetic research, RNA methylation is expected to achieve a new breakthrough in the treatment of myocardial infarction by stem cell transplantation.  Figures and Tables | References | Related Articles | Metrics

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Stem cell transplantation for diabetic patients with lower-extremity arterial disease: a meta-analysis Xia Wenshen, He Renjiao, Ai Jinwei, Wang Jun, Li Desheng, Pei Bin 2021, 25 (19):  3110-3116.  doi: 10.3969/j.issn.2095-4344.3524 Abstract ( 317 )   PDF (804KB) ( 37 )   Save OBJECTIVE: Stem cell transplantation has been used in the clinical treatment of diabetic lower limb vascular diseases. The conclusions were inconsistent due to the small sample size of each study. This article systematically reviewed the safety and efficacy of stem cells transplantation for diabetic patients with lower-extremity arterial disease.  METHODS: PubMed, The Cochrane Library (Issue 11, 2019), EMbase, CNKI, CBM, VIP and Wanfang databases were electronically searched to collect randomized controlled trials of stem cell transplantation for diabetic patients with lower-extremity arterial disease from inception to December 10, 2019. Two reviewers independently screened literature, extracted data and assessed risk of bias of included studies. Meta-analysis was then performed using RevMan 5.3 software.  RESULTS:  A total of 13 randomized controlled trials involving 546 patients, with 287 patients in stem cell transplantation group and 259 patients in conventional treatment group were included. The meta-analysis results showed that compared with the conventional treatment group, stem cell transplantation could significantly decrease the rate of lower limb amputation (RR=0.29, 95%CI: 0.10-0.84, P=0.02], improve the collateral angiogenesis (RR=3.16, 95%CI: 2.12-4.70, P < 0.000 01), increase ankle brachial pressure index (MD=0.17, 95%CI: 0.10-0.24, P < 0.000 01), transcutaneous oxygen pressure (MD=7.71, 95%CI: 3.99-11.43, P < 0.000 01), skin temperature (MD=1.90, 95%CI: 1.28-2.53, P < 0.000 01) and intermittent limp distance (MD=150.61, 95%CI: 43.49-257.74, P=0.006), reduce the scores of rest pain (MD=-1.16, 95%CI: -1.92 to -1.30, P < 0.000 01), and cold feeling (MD=-2.00, 95%CI: -2.49 to -1.50, P < 0.000 01). No severe complications such as death, neoplasm, or hepatorenal function impairment were observed in all of our included studies.  CONCLUSION: Stem cell transplantation maybe an effective and safe therapeutic method for diabetic patients with lower-extremity arterial disease. However, due to the limited quantity and quality of included studies, more high-quality, long-term follow-up and large sample size randomized controlled trials are needed to confirm the above conclusions. Figures and Tables | References | Related Articles | Metrics