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    08 May 2021, Volume 25 Issue 13 Previous Issue    Next Issue
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    Bone marrow mesenchymal stem cells from pigs inhibit inflammatory response induced by lipopolysaccharide and improve islet cell dysfunction in pigs
    Yuan Baohong, Zhao Weishan, Wang Ruotian, Guan Aoran, Wang Yu, Li Ruhong
    2021, 25 (13):  1969-1975.  doi: 10.3969/j.issn.2095-4344.2195
    Abstract ( 226 )   PDF (2663KB) ( 35 )   Save
    BACKGROUND: Porcine pancreatic islet transplantation is a common treatment for diabetes mellitus, but inflammatory reaction and oxidative stress can lead to poor long-term effect. It has been confirmed that transplantation of porcine bone marrow mesenchymal stem cells with islets can improve graft function. However, it has not been reported that porcine bone marrow mesenchymal stem cells regulate the expression of miR-299-5p in islet cells to regulate the function and survival rate of islet β cells.
    OBJECTIVE: To investigate the effects of bone marrow mesenchymal stem cells in pigs on functional impairment of islet in pig by regulating the JNK/C-Jun pathway through the miR-299-5p/SIAH1 molecular axis. 
    METHODS:  Lipopolysaccharide was used to induce functional impairment of porcine islet cells, which were co-cultured with bone marrow mesenchymal stem cells for 24 hours. Interleukin-6, interleukin-1β, tumor necrosis factor-α, reactive oxygen species, superoxide dismutase and insulin levels in islet cells were detected by ELISA. Hoechst 33258 staining was used to observe apoptosis. Annexin V-FITC/PI was used to detect the apoptosis rate of porcine islet cells. Western blotting was used to detect the expression of SIAH1 and proteins associated with JNK/C-Jun pathway. The expression of miRNAs in porcine islet cells was detected by qPCR. The dual-luciferase reporter gene assay verified the targeting relationship between miR-299-5p and SIAH1.  
    RESULTS AND CONCLUSION: (1) Bone marrow mesenchymal stem cells in pigs inhibited the up-regulation of interleukin-6, interleukin-1β, tumor necrosis factor-α, reactive oxygen species and pro-apoptotic effects, and also inhibited the down-regulation of superoxide dismutase and insulin secretion induced by lipopolysaccharide. (2) Bone marrow mesenchymal stem cells of pigs significantly upregulated miR-299-5p expression. miR-299-5p inhibited activation of the JNK/C-Jun pathway by down-regulating SIAH1 expression. (3) Results indicate that bone marrow mesenchymal stem cells of pigs inhibit the activation of the JNK/C-Jun pathway, inhibit the inflammatory response, oxidative stress and apoptosis of islet cells in pigs, and promote the secretion of insulin by regulating the miR-299-5p/SIAH1 axis, hereby improving the functional damage of porcine islet cells.

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    Platelet-derived growth factor BB promotes the proliferation of bone marrow mesenchymal stem cells of Sprague-Dawley rats
    Jiang Tao, Wu Shuo, Li Zhiqiang, Shou Xi, Mayire·Nuermaimaiti, Ma Chuang, Wei Qin
    2021, 25 (13):  1976-1981.  doi: 10.3969/j.issn.2095-4344.2188
    Abstract ( 239 )   PDF (1559KB) ( 22 )   Save
    BACKGROUND: It has been reported that platelet-derived growth factor BB secreted by mouse osteoclasts can promote the formation of osteoblasts and vascular cells, but the optimal concentration and time of platelet-derived growth factor BB on bone marrow mesenchymal stem cells are not clear. 
    OBJECTIVE: To investigate the optimal concentration and intervention time of platelet-derived growth factor BB to promote the proliferation of bone marrow mesenchymal stem cells in Sprague-Dawley rats. 
    METHODS:  Sprague-Dawley rat bone marrow mesenchymal stem cells were isolated and cultured in vitro. The third generation of cells was identified by surface cytometry CD45, CD29 and CD34, and bone marrow mesenchymal stem cells with higher purity were selected for intervention experiments. The selected cells were seeded in 96-well culture plates. Cells in the control group were cultured with α-MEM complete medium. Cells in the remaining groups were cultured with α-MEM complete medium combined with 6.25, 12.5, 25, 50, and 100 μg/L platelet-derived growth factor BB. CCK-8 method was used to detect the proliferation of cells in each group at 1, 3, 5, and 7 days, and the optimal time and concentration of platelet-derived growth factor BB for bone marrow mesenchymal stem cells intervention. 
    RESULTS AND CONCLUSION: (1) Flow cytometry: mesenchymal stem cells were positive for CD29 (94.6%), negative for CD45 (3.3%), and negative for CD34 (0.2%). Rat bone marrow mesenchymal stem cells with higher purity were obtained. (2) Repeated measurement analysis of variance showed that the absorbance of platelet-derived growth factor BB changed at different times after intervention with bone marrow mesenchymal stem cells. The proliferation effect was the strongest on the third day, and the difference was statistically significant (F=27.773, P < 0.001). LSD method for a pairwise comparison of the grouping factors showed that 25 μg/L platelet-derived growth factor BB group had statistically significant differences with the other five groups (P < 0.05). (3) It was concluded that the 25 μg/L platelet-derived growth factor BB group intervened bone marrow mesenchymal stem cells had a proliferation effect on cells on the third day. Platelet-derived growth factor BB concentration greater than 50 μg/L can promote apoptosis.
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    Effects of dynamic pressure on the proliferation and mechanical properties of rabbit adipose mesenchymal stem cells transfected with insulin-like growth factor-1
    Zhang Chuanhui, Li Jianjun, Yang Jun
    2021, 25 (13):  1982-1987.  doi: 10.3969/j.issn.2095-4344.3514
    Abstract ( 231 )   PDF (2287KB) ( 24 )   Save
    BACKGROUND: Adipose mesenchymal stem cells are currently recognized as excellent seed cells for tissue engineering cartilage. Gene transfection technology can effectively induce them to differentiate into cartilage. The bioreactor is used to simulate the mechanical environment in vivo. It is a new idea for the majority of scholars to explore the construction of tissue engineering cartilage in vitro.  
    OBJECTIVE: To investigate the effects of cyclic dynamic compressive stress combined with insulin-like growth factor-1 gene transfection on the proliferation and elastic modulus of rabbit adipose mesenchymal stem cells implanted in chitosan/gelatin scaffold.
    METHODS:  Rabbit adipose mesenchymal stem cells were transfected with pcDNA3.1-IGF-1 gene mediated by liposome. The stable transfected cell lines were screened by G418. The adipose mesenchymal stem cells transfected with or without insulin-like growth factor-1 gene were inoculated in chitosan/gelatin scaffold at the density of 5×1010 L-1 for 2 days, and cultured under dynamic pressure (2% at 1 Hz, 4 hours per day) or static culture conditions for 7 days, respectively. The morphological changes of the cell/scaffold complex were observed by scanning electron microscope, Masson trichrome staining and alcian blue staining. The cell proliferation curve was drawn by MTT assay. The cell proliferation efficiency and distribution were evaluated by CM-Dil fluorescence-labeling method, and the content of total glycosaminoglycan was quantitatively determined by DMMB. The differences of type II collagen among different groups were compared with real time PCR. Compressive mechanical properties of the cell/scaffold constructs were assessed using a BioDynamicTM mechanical tester, and the corresponding elastic modulus was calculated.
    RESULTS AND CONCLUSION: Dynamic pressure combined with insulin-like growth factor-1 transfection could significantly improve the cell proliferation ability of the cell/scaffold complex; the cell distribution was more uniform; glycosaminoglycan and collagen secretion in the cartilage-specific extracellular matrix were increased; the expression levels of type II collagen were up-regulated; and the mechanical properties were significantly improved. The cell proliferation and elastic modulus of insulin-like growth factor-1 group were better than those of single pressure group, but the distribution of cells in scaffolds was more uniform under dynamic pressure. The results indicate that both dynamic pressure and insulin-like growth factor-1 gene transfection can significantly improve the proliferation and mechanical properties of rabbit adipose mesenchymal stem cells; the two have synergistic effect. 

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    Effect of icaritin on ferroptosis of bone marrow mesenchymal stem cells and their differentiation into cardiomyocytes
    Li Qi, Sun Guicai
    2021, 25 (13):  1988-1992.  doi: 10.3969/j.issn.2095-4344.2194
    Abstract ( 267 )   PDF (861KB) ( 30 )   Save
    BACKGROUND: Iron accumulation or iron overload is closely related to the proliferation and apoptosis of bone marrow mesenchymal stem cells, which may play an important role in the pathological process of cardiovascular diseases.
    OBJECTIVE: To investigate the regulatory effect of icariin on ferroptosis of bone marrow mesenchymal stem cells and its differentiation into cardiomyocytes. 
    METHODS:  Taking bone marrow mesenchymal stem cells as the research object, the blank group was cultured for 14 days. The model group was treated with  0.4 μmol/L Erastin for 14 days to establish ferroptosis model. The treatment group was treated with 80 nmol/L icariin and 0.4 μmol/L Erastin for 14 days. CCK-8 method was used to detect the proliferation of cells in each group, and the levels of malondialdehyde and superoxide dismutase were detected by related kits. Western blot assay was used to detect the expression of TFR1, FPN1, Bcl-2 and Bax protein. RT-PCR was used to detect the mRNA expression of GATA4 and cTnT. 
    RESULTS AND CONCLUSION: (1) Compared with the model group, the cell proliferation ability of the treatment group was significantly improved (P < 0.05). (2) Compared with the model group, the level of malondialdehyde in the lysate of bone marrow mesenchymal stem cells in the treatment group was significantly lower (P < 0.05), while the level of superoxide dismutase was significantly increased (P < 0.05). (3) Compared with the model group, TFR1 protein expression was decreased (P < 0.05), FPN1 protein expression was increased (P < 0.05), and Bcl-2/Bax protein expression ratio was increased significantly (P < 0.05) in the treatment group. (4) Compared with the model group, the expression of GATA4 and cTnT mRNA was significantly increased in the treatment group (P < 0.05). (5) The results showed that icariin could inhibit the ferroptosis of bone marrow mesenchymal stem cells and improve the ability of bone marrow mesenchymal stem cells to differentiate into cardiomyocyte-like cells.  
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    Efficacy and influencing factors of autologous hematopoietic stem cell transplantation in the treatment of malignant lymphoma
    Cao Linlin, Ding Kaiyang, Song Hao, Wu Guolin, Hu Maogui, Fan Dandan, Zhou Chenyang, Wang Cuicui, Feng Yuanyuan
    2021, 25 (13):  1993-1998.  doi: 10.3969/j.issn.2095-4344.3510
    Abstract ( 363 )   PDF (880KB) ( 23 )   Save
    BACKGROUND: Chemotherapy, local radiotherapy, autologous peripheral blood stem cell transplantation and cellular immunotherapy are the treatment options for lymphoma. High-dose chemotherapy combined with autologous hematopoietic stem cell transplantation can significantly prolong the survival time and improve the prognosis of patients. It is recommended as the first-line treatment for relapsed refractory and (or) highly invasive lymphoma.
    OBJECTIVE: To explore the influencing factors of high-dose chemotherapy combined with autologous hematopoietic stem cell transplantation in lymphoma.
    METHODS:  The clinical records of 74 lymphoma patients after high-dose chemotherapy combined with autologous hematopoietic stem cell transplantation in Transplantation Ward, Department of Hematology, West District of The First Affiliated Hospital of University of Science and Technology of China from October 2015 to March 2020 were collected and analyzed retrospectively to evaluate efficacy and prognostic factors of autologous hematopoietic stem cell transplantation for lymphoma. 
    RESULTS AND CONCLUSION: (1) The follow-up period was up to May 15, 2020. The median time from diagnosis to transplantation was 8(3-83) months, and the median follow-up time was 17(2-59) months. (2) All patients obtained hematopoietic reconstruction after transplantation. The median time for granulocyte implantation was +10(+8-+17) days, and the median time for platelet implantation was +12(+9-+22) days. (3) There were 60 cases of progression-free survival after transplantation, 13 cases of recurrence, 11 of the relapsed patients died, and 1 died of lung infection 11 months after transplantation. (4) All four patients with progression disease before transplantation died within 7 months after transplantation due to the progression of the primary disease. (5) The 2-year overall survival rate after receiving autologous hematopoietic stem cell transplantation was 78.5%; the 2-year progression-free survival rate was 75.8%. Patients with international prognostic index ≤ 2 points before transplantation and international prognostic index > 2 points had 93.9% and 66.4% overall survival at 2 years after transplantation (P=0.003); progression-free survival rates at 2 years were 85.6% and 65.5% (P=0.017), respectively. (6) The two-year overall survival rates of patients with bone marrow invasion and no bone marrow invasion before transplantation were 55.5% and 91.9% (P=0.001) respectively. The 2-year progression-free survival rates were 53.1% and 88.7% (P < 0.001), respectively. (7) The 2-year overall survival rate of patients in clinical staging (stages I and II) was better than that in clinical staging (stages III and IV) (100% vs. 82.5%, P=0.026). The 2-year progression-free survival rate of first-line consolidation patients was better than that of rescue group (84% vs. 48.9%, P=0.01). There was no statistically significant difference in the effects of patient age and degree of remission before transplantation on progression-free survival and overall survival. (8) Results found that high-dose chemotherapy combined with autologous hematopoietic stem cell transplantation could significantly improve the survival and prognosis of patients with lymphoma, and had high safety. It can be used as a safe and effective treatment for lymphoma. International prognostic index score, the presence or absence of bone marrow invasion, the timing of transplantation, and the stage of primary disease are relative to the prognosis of involved patients.  

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    Muscle mass evaluation and influencing factors of sarcopenia in allogeneic hematopoietic stem cell transplantation patients
    Zhang Wenjian, Ma Lingfu, Wang Zhimin, Mo Wenjian, Zhou Ruiqing
    2021, 25 (13):  1999-2004.  doi: 10.3969/j.issn.2095-4344.2197
    Abstract ( 259 )   PDF (657KB) ( 26 )   Save
    BACKGROUND:  Muscle tissue plays an important role in completing exercise, maintaining body position and maintaining homeostasis in the body. Muscle quality assessment and intervention can help to improve the quality of life of patients and shorten the length of hospital stay, which has become a research hotspot in recent years. 
    OBJECTIVE: To explore the related influencing factors of muscle mass decline by systematic assessment of limb muscle mass in patients undergoing allogeneic hematopoietic stem cell transplantation.
    METHODS: 146 patients who underwent allogeneic hematopoietic stem cell transplantation were selected as the study subjects. The general information questionnaire was used to collect patients’ age, sex, and education degree. Muscle mass was measured by bioelectrical impedance analysis. Patient’ body mass index, arm muscle circumference, triceps skinfold thickness, body fat rate, conditioning regimen, antithymocyte globuin dose, HLA matching, graft source, albumin, prealbumin and total protein, and ECOG score were collected. The t test, chi square test and binary logistic regression analysis were used to analyze appendicular skeletal muscle. The study was approved by the Ethics Committee of Guangzhou First People’s Hospital. All patients agreed to participate in the study and signed informed consent.
    RESULTS AND CONCLUSION: (1) Muscle mass loss was observed in 89 patients (60.9%) of allogeneic hematopoietic stem cell transplantation, including 51 males and 38 females. Compared with the reference values of the Chinese normal population, it was found that allogeneic hematopoietic stem cell transplantation patients showed lower levels of muscle mass, arm muscle circumference and triceps skinfold thickness, but body fat rate increased significantly, with statistically significant differences (P < 0.05). (2) The patients were divided into the low muscle mass group and the normal muscle mass group. The differences in body weight and body mass index between the two groups were statistically significant (P < 0.05), but the differences in biochemical indexes such as albumin, prealbumin and total protein were not statistically significant (P > 0.05). (3) A single factor comparison of muscle mass showed that there were statistically significant differences in weight, body mass index, conditioning regimen and ECOG score (P < 0.05). Binary logistic regression showed that high body mass index was a protective factor of muscle mass in patients with allogeneic hematopoietic stem cell transplantation (OR=52.804, P < 0.05), and high ECOG score was a risk factor (OR=0.458, P < 0.05). (4) Results indicate that allogeneic hematopoietic stem cell transplantation patients generally have decreased muscle mass in their extremities, and muscle mass can reflect the nutritional status of patients earlier than blood biochemical indicators such as albumin, providing earlier warning for nutritional intervention. Therefore, early evaluation of skeletal muscle mass in allogeneic hematopoietic stem cell transplantation patients should be conducted. 

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    Effects of conditioned medium of human periodontal ligament stem cells on proliferation and osteogenic differentiation of inflammatory tissue-derived human periodontal ligament stem cells
    Liu Yan, Gao Xiang, Zhao Xiaoxia, Chen Qingyu, Gao Junwu
    2021, 25 (13):  2005-2010.  doi: 10.3969/j.issn.2095-4344.3506
    Abstract ( 216 )   PDF (1527KB) ( 20 )   Save
    BACKGROUND: The conditioned medium rich in bioactive substances can maintain the stability of proliferation and biological characteristics of stem cells. Whether the conditioned medium of human periodontal stem cells derived from healthy tissues can affect the proliferation and osteogenesis of human periodontal stem cells derived from inflammatory tissue is significant for periodontal tissue regeneration and reconstruction.  
    OBJECTIVE: To investigate the effect of human periodontal stem cells-conditioned medium derived from healthy tissue on proliferation and osteogenic differentiation of human periodontal stem cells derived from inflammatory tissue.
    METHODS: HPDLSCs from normal periodontal ligaments of healthy adults were isolated, purified and cultured in vitro. Human periodontal stem cells-conditioned medium was obtained by collecting the supernatants from the serum free medium which was used for the third generation cells grown up to 80% of the bottom of the bottle after 24 hours cultivation. Human periodontal stem cells derived from inflammatory tissue were obtained from pericementum of periodontitis patients, and cultured by using limiting dilution assay. Human periodontal stem cells derived from inflammatory tissue were separately cultured under conditioned medium treatment group (conditioned medium containing 50% human periodontal ligament stem cells + 50% conventional medium) and control group (conventional medium). Protein expression levels of vimentin, Pan Cytokeratin, and stromal cell antigen STRO-1 were identified by immunofluorescence staining. The proliferative activity of cells was analyzed by MTT assay and flow cytometry. After osteogenesis in vitro, alkaline phosphatase activity and the expression levels of three osteogenesis related genes (Runx2, OPN, and OCN) were detected using alkaline phosphatase kit and RT-PCR, respectively in both groups.
    RESULTS AND CONCLUSION: (1) Both groups of cells were in accordance with the morphological characteristics of adult stem cells, showing long fusiform or polygonal shapes. There was no significant difference in cell morphology between the two groups under inverted phase contrast microscope. (2) The immunofluorescence staining showed that cells in both groups were positive for the specific antibodies of vimentin and STRO-1, but negative for the specific antibody of Pan Cytokeratin. (3) The results of MTT assay showed that after 3, 5 and 7 days, the proliferative activity of conditioned medium treatment group was higher than that of control group (P < 0.01). (4) Cell cycle analysis showed that compared with the control group, the number of cells in G2/M phase and S phase in conditioned medium treatment group increased significantly (P < 0.05). (5) At 5 and 7 days of osteogenic induction in vitro, alkaline phosphatase activity of conditioned medium treatment group was higher than that of control group (P < 0.05). (6) After 21 days of osteogenic induction, the expression levels of osteogenic related genes Runx2, OPN, and OCN in conditioned medium treatment group were significantly higher than those in control group (P < 0.01, P < 0.05). (7) In conclusion, human periodontal stem cells-conditioned medium derived from healthy tissues can enhance the proliferation and osteogenic differentiation of human periodontal stem cells derived from inflammatory tissue. 

    中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程

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    Therapeutic mechanism of adipose mesenchymal stem cells in mice with systemic sclerosis
    Zhang Jingying, Sun Xiaolin, Geng Lixia
    2021, 25 (13):  2011-2017.  doi: 10.3969/j.issn.2095-4344.3512
    Abstract ( 208 )   PDF (3343KB) ( 28 )   Save
    BACKGROUND: Although clinical studies have found that autologous adipose mesenchymal stem cells can effectively reduce facial fibrosis in patients with radiation-induced systemic sclerosis, but the mechanism of action has not been thoroughly analyzed. 
    OBJECTIVE: To study the mechanism of action of adipose mesenchymal stem cells on bleomycin-induced systemic sclerosis in mice. 
    METHODS:  Forty SPF C57BL/6J female mice aged 6-8 weeks were randomly assigned to normal control group, adipose mesenchymal stem cells group, bleomycin group, and PBS group. Mice in the latter three groups were subjected to subcutaneous injection with bleomycin every other day for 28 days, and mouse models of systemic sclerosis were established. After successful model establishment, mice in the adipose mesenchymal stem cells group were subcutaneously injected with adipose mesenchymal stem cells; mice in the PBS group were subcutaneously injected with PBS; the treatments lasted for 14 days. Enzyme-linked immunosorbent assay was used to determine the levels of serum interleukin-17, transforming growth factor-β, interleukin-6, and tumor necrosis factor-α. Hematoxylin-eosin staining and Masson staining were utilized to measure histopathological changes in the skin and lung of systemic sclerosis mice. Immunofluorescence method was applied to examine collagen I, III, and V and CD31 expression levels in the skin and lung. 
    RESULTS AND CONCLUSION: (1) Compared with the bleomycin group, the expression levels of interleukin-17, transforming growth factor-β, interleukin-6, and tumor necrosis factor-α were significantly decreased in the adipose mesenchymal stem cells group (P < 0.01). (2) Compared with the normal control group, the skin dermis of mice was thickened; inflammatory cells infiltrated; skin appendages reduced; the alveoli were atrophic and collapsed; with a lot of inflammatory cell infiltration, pulmonary arteriole wall thickening, microvascular basement membrane thickening, and fibrinoid necrosis, and the inflammatory symptoms improved after treatment in the adipose mesenchymal stem cells group. (3) Compared with the normal control group, the skin and lung tissues of bleomycin group mice showed a large aggregation of collagen fibers, and the collagen fibers were reduced after adipose mesenchymal stem cells treatment. (4) After treatment with adipose mesenchymal stem cells, the expression levels of collagen I, III, and V were decreased in the skin and lung tissue of mice, but the expression of CD31 in the skin tissues was increased in the bleomycin group (P < 0.01). (5) The results suggested that adipose mesenchymal stem cells can regulate the immune response of bleomycin mice and reduce fibrosis, inflammation and vascular lesions.

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    A downtrend of mesenchymal cells derived from the second heart field and cardiac neural crest in the outflow tract of Cx43 knockout embryonic mouse heart
    Li Hang, Jing Ya, Li Yunhua, Li Hairong, Yang Yanping
    2021, 25 (13):  2018-2024.  doi: 10.3969/j.issn.2095-4344.2992
    Abstract ( 223 )   PDF (8388KB) ( 37 )   Save
    BACKGROUND: Cx43 plays an important role in human congenital heart disease. However, there is still no consistent conclusion about the formation mechanism of cardiac malformation in Cx43 knockout mouse embryos.
    OBJECTIVE: To investigate the cardiac development defects and the migration and differentiation of progenitor cells of the second heart field and cardiac neural crest in Cx43 knockout mouse embryo.
    METHODS: Serial sections of Cx43 gene knockout homozygous (Cx43-/-) mouse and Cx43 wild-type (Cx43+/+) mouse embryos from embryonic day (ED) 10  to ED13 were made for immunohistochemical and immunofluorescent staining, and three-dimensional reconstruction of the heart. 
    RESULTS AND CONCLUSION: (1) In Cx43 gene knockout mouse embryos at ED10-ED11, Isl1 positive second heart field cells in the ventral mesenchyme of the foregut extended through the area between the bilateral arch arteries to the dorsal wall of pericardial cavity. Meanwhile, Isl1 positive cells in the core mesenchyme of the branchial arches were continuous with those in the dorsal wall of pericardial cavity and the distal wall of the outflow tract. At ED13, the distribution of Isl1 positive cells was observed in the wall of the ascending aorta and pulmonary trunk as well as the wall of the left and right outflow tracts of the septated ventricles. However, compared with wild-type mouse embryos, fewer Isl1 positive second heart field cells were found in Cx43 gene knockout mouse embryos (P < 0.01). (2) During ED10 to ED11, Ap2α positive neural crest cells were still found in the wall of the arch artery and the dorsal and ventral walls of the aortic sac in Cx43 gene knockout mouse embryos, but the number of neural crest cells was less than that of wild-type mouse embryos (P < 0.01). (3) These results indicate that the migration path and distribution pattern of Isl1 positive second heart field cells and Ap2α positive cardiac neural crest cells are similar between the Cx43 gene knockout and wild-type mouse embryos, but the number of two kinds of migrating cells is reduced after Cx43 gene knockout. This suggests that in addition to cardiac neural crest derived cells, the decrease of second heart field progenitor cells might be involved in the formation of outflow tract malformations in Cx43 knockout mouse embryos.
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    Effect of immature dendritic cells derived from bone marrow on rejection of orthotopic liver transplantation in rats
    Li Liqiang, Jiao Longxing, Zhang Wu, Yan Wentao, Li Jian, Li Minghao
    2021, 25 (13):  2025-2029.  doi: 10.3969/j.issn.2095-4344.3509
    Abstract ( 304 )   PDF (1526KB) ( 17 )   Save
    BACKGROUND: Immature dendritic cells have strong antigen uptake and processing ability, but the lack of a variety of costimulatory molecules cannot activate and proliferate initial T cells to produce immune response, which can lead to T cell anergy, thus inducing low immune response or antigen immune specific tolerance. Simultaneously, immature dendritic cells can induce hyporeactivity of allogeneic antigen-specific T cells, thus prolonging the survival time of transplanted organs.  
    OBJECTIVE: To investigate the effect of immature dendritic cells on liver rejection after orthotopic liver transplantation in rats and its mechanism.
    METHODS:  According to the weight of DA and Lewis rats, the rats were randomly divided into three groups, and the liver transplantation model of DA-Lewis rats was established by “two-cuff” method. The rats of control group received no measures. The rats of cyclosporine group were treated with 10 mg/kg 
    cyclosporine from the second day after operation, once a day, for 7 days. The rats of the immature dendritic cell group were injected with 1×106 immature dendritic cells from bone marrow of DA rats one day before operation through dorsal penile vein; the injection was repeated twice with an interval of 10 minutes. The livers of all these rats were removed 7 days after operation. Hematoxylin-eosin staining was used to observe the pathological changes. The mRNA and protein expressions of SHIP, AKT, IKK and IKβ in these three groups were detected by qRT-PCR and western blot assay.
    RESULTS AND CONCLUSION: (1) Compared with the control group, the survival time of cyclosporine group and immature dendritic cell group was significantly longer (P < 0.05). (2) In cyclosporine group and immature dendritic cell group, the number of infiltrating mononuclear cells and lymphocytes in the portal area of liver tissue was less, the structure of hepatic lobule was not significantly damaged, and the inflammatory cells in hepatic artery, portal vein and bile duct were significantly less than those in control group, which did not reach the level of severe acute rejection. (3) Compared with the control group, the mRNA expression of IKβ in the cyclosporine group and immature dendritic cell group was increased, while the mRNA expression of SHIP, AKT and IKK significantly decreased (P < 0.05). (4) Compared with the control group, the expression of SHIP and IKβ protein significantly increased, IKK and AKT protein significantly decreased in the immature dendritic cell group (P < 0.05). Compared with the control group, the expression of SHIP and IKK protein significantly decreased, AKT and IKβ protein expression significantly increased in the cyclosporine group (P < 0.05). (5) Results confirm that immature dendritic cells can slow down the severe acute rejection, delay the survival time of liver and reduce the T cell immune response ability of allogeneic liver transplantation. 

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    Nerve growth factor interferes with proliferation and alpha-actin expression of skeletal muscle satellite cells in rats
    Yan Nan, Si Xiaofeng, Zeng Liang, Tian Wei, Shan Guangdong, Xiong Lishuo, Yang Weijie, Wang Zhengdong
    2021, 25 (13):  2030-2035.  doi: 10.3969/j.issn.2095-4344.3513
    Abstract ( 199 )   PDF (3001KB) ( 26 )   Save
    BACKGROUND: Clinical studies have confirmed that the injection of nerve growth factor into the nerve damage site can improve the motor function of skeletal muscle.
    OBJECTIVE: To observe the effect of nerve growth factor on the proliferation of primary skeletal muscle satellite cells in rats. 
    METHODS:  The original generation of rat skeletal muscle satellite cells were cultivated by the tissue block method, and the third generation of skeletal muscle satellite cells were divided into three groups. The control group was added with culture medium; the low concentration group and the high concentration group were added with culture medium containing 10, 20 U/mL nerve growth factors, respectively. At 2, 4 and 6 days after culture, the cell morphology was observed by inverted phase contrast microscope and hematoxylin-eosin staining, and the expression of α-actin was observed by immunohistochemistry. At 1, 2, 3, and 4 days after culture, CCK-8 assay was used to detect the cell proliferation activity. 
    RESULTS AND CONCLUSION: (1) Inverted phase contrast microscope displayed that with the increase of culture time, the number of skeletal muscle satellite cells in each group increased gradually, and the cell morphology gradually changed from round to fusiform, spindle or polygonal, and gradually fused and arranged along the same direction, and the number of cells in high concentration group was more than that in low concentration group and control group 
    (P < 0.05). (2) Hematoxylin-eosin staining showed that the outline of satellite cells in skeletal muscle of each group was clear and densely distributed, and the nucleus was large and deeply stained; there was no significant difference among groups. (3) Immunohistochemical results showed that the expression of α-actin in skeletal muscle in each group was positive, but there was no statistical difference in the optical density of α-actin positive particles in each group (P > 0.05). (4) The CCK-8 assay results showed that cell viability of low and high concentration groups was higher than that of control group (P=0.000). (5) Above results confirm that high and low concentrations of nerve growth factors could promote the proliferation of skeletal muscle satellite cells, but had no effect on the expression of α-actin in skeletal muscle satellite cells. 
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    Exosomal miR-1307 of osteosarcoma and the proliferation and apoptosis of osteosarcoma cells
    Han Fei, Pu Peidong, Ma Qingyuan, Zhu Zhoujun, Wang Mengyu Wang Chao, Shi Chong, Shi Chenhui, Wang Weishan
    2021, 25 (13):  2036-2042.  doi: 10.3969/j.issn.2095-4344.2185
    Abstract ( 209 )   PDF (1736KB) ( 43 )   Save
    BACKGROUND: Studies have shown that the occurrence of osteosarcoma is associated with abnormal expression of various microRNAs (miRNAs). Exosomes (Exos) containing miRNAs get much more attentions in intracellular communications. 
    OBJECTIVE: To investigate the effects of exosomal miR-1307 from osteosarcoma on proliferation and apoptosis of osteosarcoma cells and its mechanism. 
    METHODS:  Human osteosarcoma cell lines (143B, MG63, U2OS, Saos-2 and SW1353) and human normal osteoblastic cell line (hFOB 1.19) were purchased. The expression level of miR-1307 in five kinds of osteosarcoma cell lines and normal osteoblastic cell line was detected by qRT-PCR. Finally, SW1353 cell line was selected for functional verification of osteosarcoma cells. Osteosarcoma cells and normal osteoblasts were cultured. Osteosarcoma exosomes and normal osteoblastic exosomes were extracted by differential centrifugation. Then miR-1307 inhibitor and miR-NC mimic were transfected into SW1353 osteosarcoma cells and normal osteoblasts, and then SW1353 osteosarcoma cell exosomes and normal osteoblast exosomes were extracted. The above exosomes (25 mg/L) were added to SW1353 osteosarcoma cells to intervene for 24 hours. Cell proliferation assay and flow cytometry were used to observe the proliferation and apoptosis of osteosarcoma cells. Targetscan, miRBase and miRDIP databases were used to predict the target genes of miR-1307. The activity of luciferin was assayed by luciferase reporter gene. mRNA and protein expression levels of AGAP1 were assayed by qRT-PCR and western blot assay in osteosarcoma cells.   
    RESULTS AND CONCLUSION: (1) Compared with hFOB 1.19-exosomes of osteoblasts, SW1353 osteosarcoma cell exosomes significantly promoted the proliferation and inhibited the apoptosis of osteosarcoma cells (P < 0.01). Compared with SW1353 osteosarcoma cell exosomes, the level of miR-1307 in SW1353 osteosarcoma cell exosomes was down-regulated; the proliferation of osteosarcoma cells was significantly decreased but the apoptosis rate was significantly increased (P < 0.01). (2) AGAP1 was verified as a direct target gene of miR-1307. Compared with miR-NC, miR-1307 significantly inhibited the mRNA and protein levels of AGAP1 (P < 0.01). Compared with miR-NC, miR-1307 significantly inhibited the luciferase activity of wild-type PGLO-AGAP1-WT 3'-UTR (P < 0.05). (3) The results show that exosomal miR-1307 of osteosarcoma promoted the proliferation and inhibited the apoptosis of osteosarcoma cells via targeting AGAP1.
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    Difference in the culture of dorsal root ganglion cells in serum-free medium and serum medium
    Xu Jinhui, Qin Xuzhen, Zhang Hongcheng, Ma Yanxia, Qi Shibin, Saijilafu
    2021, 25 (13):  2043-2048.  doi: 10.3969/j.issn.2095-4344.2191
    Abstract ( 197 )   PDF (1847KB) ( 22 )   Save
    BACKGROUND: Both serum-free and serum media have been used to culture dorsal root ganglion cells, but the difference between the two remains unclear.
    OBJECTIVE: To explore whether serum-free medium can completely replace serum medium for culture of dorsal root ganglion cells. 
    METHODS:  The dorsal root ganglion of ICR mice at 8-10 weeks was taken and treated with collagenase and trypsin. After that, the mice were divided into the electroporation + serum group, electroporation + serum-free group, non-electroporation + serum group and non-electroporation + serum-free group. In the electroporation groups, the dorsal root ganglion cells were transfected with electroporation buffer and enhanced green fluorescent protein particles. Cells were cultured for three days. After Tuj1 antibody staining, in the non-electroporation + serum group and non-electroporation + serum-free group, axon branches, axon regeneration length, number of cell survival and the expression of proteins related to axon regeneration were counted. In the electroporation + serum group and electroporation + serum-free group, axon branches, length of axon regeneration, number of cell survival, and electroporation efficiency were measured. This study was approved by the Laboratory Animal Ethics Committee of the First Affiliated Hospital of Soochow University.  
    RESULTS AND CONCLUSION: (1) In the non-electroporation + serum group and non-electroporation + serum-free group, there was no significant difference in axon branches, axon regeneration length, number of cell survival and the expression of axon regeneration related proteins (P > 0.05). (2) In the electroporation + serum group and electroporation + serum-free group, there was no significant difference in axon branches, axon regeneration length and electroporation efficiency (P > 0.05). Compared with electroporation + serum group, the number of cell survival of the electroporation + serum-free group was significantly lower (P < 0.05). (3) There was no significant change in the length of cell axon regeneration between the electroporation + serum group and the non-electroporation + serum group (P > 0.05). The number of cell survival of the non-electroporation + serum group was significantly higher than that of the electroporation + serum group (P < 0.05). (4) The results showed that, in the condition of non-electroporation, the absence of serum does not affect the culture of dorsal root ganglion in vitro, and serum-free medium can replace serum medium. However, under the condition of electroporation, the number of cell survival would be decreased without serum medium, suggesting that serum plays an important role in the culture of dorsal root ganglion in vitro under the condition of electroporation. Therefore, serum-free media cannot replace serum media.
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    Severe aplastic anemia treated with unrelated cord blood combined with matched sibling allogeneic hematopoietic stem cell transplantation
    Wei Zhongling, Jiang Yizhi, Huang Laiquan, Yan Jiawei, Yu Zhengzhi, Wang Nana, Huang Chen, Wang Ran, Huang Dongping
    2021, 25 (13):  2049-2054.  doi: 10.3969/j.issn.2095-4344.3516
    Abstract ( 286 )   PDF (756KB) ( 18 )   Save
    BACKGROUND: Sibling matched allogeneic hematopoietic stem cell transplantation is still the first-line treatment for severe aplastic anemia. However, with the increase of patients’ age, the effect of transplantation decreases significantly.
    OBJECTIVE: To explore the efficacy and safety of unrelated cord blood combined with matched sibling hematopoietic stem cell transplantation in the treatment of severe aplastic anemia. 
    METHODS:  A total of four severe aplastic anemia patients who underwent unrelated cord blood combined with matched sibling hematopoietic stem cell transplantation in First Affiliated Hospital (Yijishan Hospital) of Wannan Medical College from July 2017 to February 2018 were enrolled and their clinical data were used for retrospective analysis. 
    RESULTS AND CONCLUSION: (1) All the four patients were male. The median age was 40 years old and the median time from diagnosis to transplantation was 2.5 months. Bone marrow and peripheral blood stem cells from a sibling donor as well as a unit of unrelated cord blood with HLA matching ≥ 4/6 were applied. (2) The median stem cells of total nucleated cells and CD34+ were 13.67×108/kg and 2.7×106/kg of the sibling donor, 2.1×107/kg and 1.21×105/kg of the unrelated cord blood, respectively. (3) The median implantation time of neutrophils and platelets was +10 days and +20 days, respectively. (4) After transplantation, one patient was sibling donor chimerism while that of another three patients was double donors. At the follow-up date, among the three cases of mixed chimerism from two donors, one was completely implanted with unrelated cord blood; one was completely implanted with sibling donor; the third case had mixed chimerism with sibling donor and recipient giving up treatment because of infection. (5) Only one patient developed grade II acute graft versus host disease. The incidence of III-IV acute graft versus host disease and chronic graft versus host disease was 0%. (6) Two-year post-transplant disease free survival and overall survival rates were both 75% and graft versus host disease-free and relapse-free survival was 100%. (7) The results show that sibling allogeneic hematopoietic stem cell transplantation combined with unrelated cord blood transfusion for the treatment of older patients with severe aplastic anemia has a low incidence of graft versus host disease and a positive effect, but the dynamics for the implantation of two kinds of donor stem cells is worthy of further study. 

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    Glia maturation factor-gamma inhibits the proliferation of human colorectal cancer LoVo cells and affects the cytoskeletal motion of human umbilical vein endothelial cells
    Wang Huili, Chen Zhijiang, Wu Bingyi
    2021, 25 (13):  2055-2059.  doi: 10.3969/j.issn.2095-4344.3507
    Abstract ( 245 )   PDF (1621KB) ( 24 )   Save
    BACKGROUND: Glial maturation factor-gamma (GMFG) is one of the members of the ADF/cofilin superfamily protein in the process of cytoskeleton remodeling. It can regulate the cell movement by regulating actin-mediated cytoskeleton reorganization. The authors previously found that the high expression of GMFG is associated with the clinicopathological features of colorectal cancer patients, but the specific upstream and downstream mechanisms need to be explored.
    OBJECTIVE: To study the effects of GMFG on cytoskeleton and LoVo cell proliferation.
    METHODS:  (1) Human umbilical vein endothelial cells were inoculated in a laser confocal dish. After the cells grew stably, the correlation between the expression of GMFG and the expression of cytoskeletal protein F-actin was observed by immunofluorescence staining. Colchicine inhibited mitosis. The cells were divided into control group, 0.5 mg/L colchicine group and 1.0 mg/L colchicine group. The cell cycle was observed by flow cytometry and GMFG protein expression was observed by western blot assay. (2) Human colorectal cancer LoVo cells were inoculated in a laser confocal dish. After the cells grew stably, the correlation between GMFG expression and cell cycle was observed by immunofluorescence staining. Afterwards, siRNA was used to interfere the expression of GMFG in LoVo cells. The LoVo cells were divided into blank control group, empty transfer group and siRNA-GMFG group. The cell proliferation rate was detected by Edu assay. 
    RESULTS AND CONCLUSION: (1) In human umbilical vein endothelial cells, the expression of GMFG was associated with the cytoskeletal motion of human umbilical vein endothelial cells, and the expression of GMFG increased when the cytoskeleton retracted. After colchicine inhibited the mitosis of human umbilical vein endothelial cells, the proportion of cells in G2/M phase increased and the expression of GMFG protein decreased with the increase of colchicine dosage. (2) In LoVo cells, the expression intensity of GMFG was associated with mitosis, and the expression of GMFG was enhanced in the middle and late stages of cell mitosis. (3) After siRNA interference with GMFG in LoVo cells, the cell proliferation rate was decreased. (4) Results verify that interference with GMFG can inhibit the proliferation rate of LoVo cells of human colorectal cancer, and there is a certain correlation between cytoskeletal motion and GMFG expression. 

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    Effect and mechanism of traditional Chinese medicine for replenishing qi and promoting blood combined with bone marrow mesenchymal stem cells in promoting angiogenesis in ischemic stroke
    Fan Feiyan, Zhang Yunke
    2021, 25 (13):  2060-2069.  doi: 10.3969/j.issn.2095-4344.3505
    Abstract ( 275 )   PDF (819KB) ( 34 )   Save
    BACKGROUND: Bone marrow mesenchymal stem cells have the effect of promoting angiogenesis, and have shown a good therapeutic effect in the study of ischemic stroke. Traditional Chinese medicine for replenishing qi and activating blood also has a significant effect in promoting angiogenesis.
    OBJECTIVE: To summarize the mechanism of traditional Chinese medicine for replenishing qi and activating blood combined with bone marrow mesenchymal stem cells in promoting angiogenesis in ischemic stroke, so as to provide reference for the research and treatment of ischemic stroke.
    METHODS: “Bone marrow mesenchymal stem cells, angiogenesis, ischemic stroke, traditional Chinese medicine” were used as the English and Chinese key words. We searched the literatures regarding the related mechanism of angiogenesis and the literature related to angiogenesis promoted by traditional Chinese medicine combined with bone marrow mesenchymal stem cells in PubMed, CNKI and Wanfang databases from 2009 to 2020. The literatures with weak correlation and repetition were excluded, and 145 literatures were summarized and analyzed.
    RESULTS AND CONCLUSION: (1) The definition of bone marrow mesenchymal stem cells and angiogenesis and the mechanism of promoting angiogenesis were combed. (2) The related factors and signal pathways of replenishing qi and activating blood traditional Chinese medicine combined with bone marrow mesenchymal stem cells to promote angiogenesis were summarized, such as vascular endothelial growth factor, brain-derived neurotrophic factor, basic fibroblast growth factor, hypoxia-inducible factor-1α, angiopoietin, integrin αvβ3, matrix metalloproteinase-9 and Wnt signal pathway, Notch signal pathway, PI3K/Akt signal pathway and SDF-1/CXCR4 signal axis. (3) It is found that the combination of traditional Chinese medicine for replenishing qi and activating blood and bone marrow mesenchymal stem cells can promote angiogenesis and improve the therapeutic effect on ischemic stroke.
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    Important role of mesenchymal stem cells in immune tolerance induction in heart transplantation
    Mao Xin, Yu Limei, Wang Feng
    2021, 25 (13):  2070-2078.  doi: 10.3969/j.issn.2095-4344.2196
    Abstract ( 245 )   PDF (708KB) ( 29 )   Save
    BACKGROUND: Heart transplantation is an important treatment for end-stage heart disease. The use of immunosuppressive drugs is indispensable for the maintenance of transplantation. Given the enormous side effects of immunosuppressive drugs, it may even have a significant impact on the quality of life of patients. People began to explore new ways to induce transplantation tolerance to avoid the use of immunosuppressive drugs. The immunomodulation characteristics of mesenchymal stem cells have attracted the attention of researchers and a large number of related researches have been carried out.
    OBJECTIVE: To summarize and investigate the characteristics of immune regulation of mesenchymal stem cells and immune tolerance induction in heart transplantation and their relationship. 
    METHODS: We searched relevant literature in PubMed database. Key words were “stem cell; mesenchymal stem cells; MSC; MSCs; heart transplantation; cardiac allograft; heart allograft; immune tolerance; tolerance; immunological rejection”. The repetitive studies were excluded after screening, and the related literature was arranged and summarized. 
    RESULTS AND CONCLUSION:  On one hand, mesenchymal stem cells have different effects on a variety of immune cells. On the other hand, mesenchymal stem cells regulate or directly produce a large number of biological active factors so as to constitute a complex network, creating a microenvironment conducive to immune regulation. The application of mesenchymal stem cells in heart transplantation is limited to animal experiments, and the results are relatively optimistic. Researchers’ exploration of induction of immune tolerance in heart transplantation will help people to understand the field further and provide more inspiration to relevant clinicians.

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    Application and progress of umbilical cord mesenchymal stem cells in bone tissue engineering
    Han Ningning, Zuo Jinfu, Sun Miao, Tang Shengjian, Liu Fangjun
    2021, 25 (13):  2079-2086.  doi: 10.3969/j.issn.2095-4344.2193
    Abstract ( 232 )   PDF (797KB) ( 37 )   Save
    BACKGROUND: As seed cells, human umbilical cord mesenchymal stem cells have many advantages, such as a broad array of sources, easy access, low immunogenicity, osteogenic differentiation potential, high proliferation and self-renewal ability. In recent years, there are more and more reports about their application for bone tissue engineering. 
    OBJECTIVE: To summarize isolation, culture, osteogenic induction and scaffolds. 
    METHODS: The first author searched CNKI and PubMed databases with key words of “human umbilical cord mesenchymal stem cells, isolation, culture, osteogenic differentiation, scaffold, bone tissue engineering” in both Chinese and English, so as to review the relevant literature from 2004 to 2020. Finally, 104 articles were included. 
    RESULTS AND CONCLUSION: There are different methods of isolation and culture of umbilical cord mesenchymal stem cells. Serum-free or animal serum substitute culture system and co-culture technique have made great progress, and three-dimensional culture system will be the development direction in the future. The exact mechanisms of osteogenic differentiation of umbilical cord mesenchymal stem cells are unclear, which need further elucidation. To date, it is still the focus of researchers to develop composite scaffolds with better properties. Bio-printing technology has primarily solve the difficult problem of controlling precisely the complex inner structure of the scaffolds at the micron scale and fabricating individual scaffolds, bringing great hope for bone tissue engineering. The design and fabrication of scaffolds with multiple ideal compositions (including biocompatibility, high porosity at the micro and macro level, mechanical properties, related absorption and so on) and the less clinical side effects remain one of the key challenges in bone tissue engineering.

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    Role and potential of adipose-derived stem cells in cranio-maxillofacial bone regeneration
    Chen Jufang, Tian Yulou, Hao Xin
    2021, 25 (13):  2087-2096.  doi: 10.3969/j.issn.2095-4344.2192
    Abstract ( 249 )   PDF (990KB) ( 29 )   Save
    BACKGROUND: The repair of cranio-maxillofacial bone defects is still facing severe challenges, and the introduction of the concept of bone regeneration points out a new direction for this problem. Adipose-derived stem cells are easy to access and have strong osteogenic differentiation capacity, which are considered as ideal seed cells for cranio-maxillofacial bone regeneration.
    OBJECTIVE: To review the influencing factors of osteogenic differentiation of adipose-derived stem cells as well as the research progress in cranio-maxillofacial bone regeneration, thus providing ideas for further study on adipose-derived stem cells in promoting cranio-maxillofacial bone regeneration. 
    METHODS: A computer-based online search of PubMed, Wanfang, and CNKI databases was performed to retrieve papers published from January 2013 to February 2020 with the search terms of “adipose-derived stem cells, cranio-maxillofacial, oral tissue regeneration, periodontal tissue regeneration, bone regeneration, bone defects, osteogenesis” in English and Chinese. Finally, 88 papers were included for summary. 
    RESULTS AND CONCLUSION: Adipose-derived stem cells can be induced to differentiate to osteoblasts and are easy to acquire in large quantities. It has a strong ability of expansion in vitro and has a broad application prospect in the field of cranio-maxillofacial bone regeneration. miRNAs/microRNAs play a role in the osteogenic differentiation of adipose-derived stem cells. The osteogenic differentiation ability of adipose-derived stem cells can be improved by the means of co-culture with other cells, combined with platelet-rich plasma or modified titanium and gene technology. Compared with conventional extracorporeal scaffolds, adipose-derived stem cells combined with injectable scaffolds have greater potential in osteogenesis. Some progress has been made in repairing cranio-maxillofacial bone defects with adipose-derived stem cells, but there is still a lack of sufficient evidence in large-scale clinical trials. 

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    Therapeutic application of adipose stem cell-free liquid extracts: skin aging, wound healing, scar recovery and nerve regeneration
    Cai Yuan, Deng Chengliang
    2021, 25 (13):  2097-2102.  doi: 10.3969/j.issn.2095-4344.2190
    Abstract ( 424 )   PDF (807KB) ( 41 )   Save
    BACKGROUND:  Adipose stem cell-free liquid extracts include adipose stem cell conditioned medium, adipose stem cell exosomes, because they do not contain cells and have the advantages of being easy to carry, store, and transport, which has gradually become one of the most promising therapies currently.
    OBJECTIVE: To review the research progress in the therapeutic application of adipose stem cell-free liquid extracts.
    METHODS: The first author searched the CNKI, Wanfang and PubMed databases for relevant articles published from January 2005 to March 2020. The key words were “adipose stem cell, stromal cell and conditioned medium”, “adipose stem cell, stromal cell and exosomes” in Chinese, and “adipose stem cell, adipose stromal cell and conditioned medium” and “adipose stem cell, adipose stromal cell and exosomes” in English. Repetitive articles and those lacking of originality were eliminated. Totally 123 articles were searched initially, and 62 articles were included in result analysis.  
    RESULTS AND CONCLUSION: Adipose stem cell-free liquid extracts have broad therapeutic potential in a variety of disease areas, such as anti-aging, wound healing, scar recovery, and nerve regeneration. However, the specific mechanism of action is not very clear, and further research is needed.

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    Pathological changes and functional reconstruction of radiation-induced salivary glands repaired by stem cells and biomaterials
    Liu Lu, Zhang Nini, Dai Min, Huang Guilin
    2021, 25 (13):  2103-2107.  doi: 10.3969/j.issn.2095-4344.3502
    Abstract ( 287 )   PDF (727KB) ( 29 )   Save
    BACKGROUND: Radiation therapy is currently one of the main treatments for head and neck cancer. Radiation therapy can kill cancer cells, but it can also damage normal cells or tissues.
    OBJECTIVE: To summarize the research progress of the changed structure of radioactive salivary glands and repair in recent years.
    METHODS: PubMed database, Wanfang database and China Full-Text Journal Database were searched. The search terms were “salivary glands; radiation injury; histological change; cell therapy” in English and Chinese. The time range was from 1991 to 2020. By reading the title, abstract and full text, repetitive studies were excluded. Finally, 57 articles were summarized. 
    RESULTS AND CONCLUSION: In the treatment of head and neck cancer patients, xerostomia caused by radioactive damage to salivary gland tissue is its typical chronic side effect. At present, it is believed that radiation will mainly affect the structure of salivary gland tissues and lead to the decline of its function, including changes in the structure of salivary glands and ducts, as well as changes in saliva secretion and excretion after blood vessel and nerve injury. However, the mechanism of radiation damage has not been pointed out. Studies have shown that stem cells derived from fat, bone marrow and human amniotic membrane epithelium can treat radiation-induced salivary gland damage, improve salivary secretion, and the transplanted cells can form secretory alveoli and duct structures in the body.

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    Effects and mechanisms of enamel matrix derivatives on osteogenic differentiation of bone marrow mesenchymal stem cells
    Meng Maohua, Li Ying, Chen Xin, Cheng Lu, Dong Qiang
    2021, 25 (13):  2108-2113.  doi: 10.3969/j.issn.2095-4344.2187
    Abstract ( 264 )   PDF (635KB) ( 31 )   Save
    BACKGROUND: Bone marrow mesenchymal stem cells have good potential for directional differentiation, but the effect and mechanism of enamel matrix derivatives on osteogenic differentiation are still unclear.
    OBJECTIVE: To summarize the latest research progress on osteogenic induction of bone marrow mesenchymal stem cells by enamel matrix derivatives.
    METHODS: Related literature from 2000 to 2020 was searched in CNKI, Wanfang Data, VIP Database, PubMed databases. The key words are “Emdogain® or enamel matrix derivatives, bone marrow mesenchymal stem cells”. The languages of the literature were set to Chinese and English. When retrieving some classic articles, the publication date could be extended appropriately. Finally, 62 English articles and 5 Chinese articles meeting the inclusion criteria were selected. 
    RESULTS AND CONCLUSION: There are different reports on the osteogenic effect of enamel matrix derivatives on bone marrow mesenchymal stem cells. Enamel matrix derivatives may enhance the osteogenic induction ability of bone marrow mesenchymal stem cells, and may enhance the osteogenic effect by affecting cells or cell membranes, but the relevant mechanism is unclear.
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    Mesenchymal stem cells in the treatment of spinal cord injury: cell therapy and combination of new drugs and biomaterials
    Qian Nannan, Zhang Qian, Yang Rui, Ao Jun, Zhang Tao
    2021, 25 (13):  2114-2120.  doi: 10.3969/j.issn.2095-4344.2184
    Abstract ( 328 )   PDF (992KB) ( 80 )   Save
    BACKGROUND: The treatment of spinal cord injury is mainly to improve the inflammation microenvironment of the injury site, as well as the regeneration and repair of neural function. Mesenchymal stem cells have the characteristics of easy proliferation in vitro, multi-directional differentiation, and suppression of secondary inflammation and immunomodulation, which makes the transplantation of mesenchymal stem cells for various refractory tissue injury diseases including spinal cord injury become a potential cell therapy. 
    OBJECTIVE: To summarize the preclinical and clinical research of mesenchymal stem cells in the treatment of spinal cord injury in recent years, and put forward the problems and development directions of mesenchymal stem cells in experimental research. 
    METHODS: We searched the articles published in Wanfang databases, CNKI and PubMed databases from 2000 to 2020. The key words were “mesenchymal stem cells, spinal cord injury, cell transplantation, immunomodulation, combination therapy, biomaterials” in Chinese and English, respectively.  
    RESULTS AND CONCLUSION: (1) Mesenchymal stem cells from different sources play the role of anti-inflammatory, inducing axon and neuron regeneration in animal models and clinical experiments, and effectively improve the neural function of the damaged area. (2) The exosomes derived from mesenchymal stem cells show the effects of immunomodulation and angiogenesis in the disease model of spinal cord injury. (3) In order to maximize the potential of mesenchymal stem cells, exploring cell pretreatment, combined with new drugs or biological materials is the research direction of mesenchymal stem cells in the treatment of spinal cord injury.  

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    Relationship between extracellular vesicles and radiation-induced tissue injury
    Liu Tao, Zhang Nini, Huang Guilin
    2021, 25 (13):  2121-2126.  doi: 10.3969/j.issn.2095-4344.3508
    Abstract ( 281 )   PDF (767KB) ( 86 )   Save
    BACKGROUND: Radiation-induced tissue injury is one of the more serious side effects of cancer patients after radiotherapy. Recent studies have shown that in the radiation-induced tissue injury model, extracellular vesicles as intercellular information carriers have two sides. On the one hand, they participate in the radiation-induced tissue injury process to mediate tissue damage. On the other hand, they participate in radiation-induced tissue injury repair by transferring biologically active substances. 
    OBJECTIVE: To summarize the damage and repair effects of extracellular vesicles from different sources on radioactive tissue damage and to clarify the relationship between extracellular vesicles and radiation-induced tissue injury, which will be beneficial to explore new treatment strategies for radiation-induced tissue injury. 
    METHODS: Databases of PubMed and CNKI were retrieved with the keywords of “extracellular vesicles, radiation-induced tissue damage (bone, brain, intestine, etc.), WNT signal” in Chinese and “radiation-induced tissue injury, extracellular vesicles, tissue repair and regeneration, vascular endothelial cells, bystander effects” in English. The retrieval time was from 1989 to 2020. After initial screening of titles and abstracts, irrelevant articles were excluded, and 61 eligible articles were included for result analysis. 
    RESULTS AND CONCLUSION: Extracellular vesicles are membrane-closed vesicles that are naturally released from cells under normal physiological or abnormal pathological conditions. On the one hand, under pathological conditions, radioactive tissue damage cannot be separated from the mediation of extracellular vesicles; on the other hand, extracellular vesicles carrying information molecules can promote the repair of radioactive tissue damage. Therefore, in the field of radioactive tissue damage repair and regeneration, extracellular vesicles have the potential to become a new cell-free therapy, but whether it can be applied to clinical use requires more in-depth research and exploration.

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    Application and prospect of induced pluripotent stem cells in tumor diseases
    Ni Jinghua, Luo Jia, Jiang Sen, Li Heng, Zhu Jianzhong
    2021, 25 (13):  2127-2132.  doi: 10.3969/j.issn.2095-4344.2189
    Abstract ( 303 )   PDF (786KB) ( 291 )   Save
    BACKGROUND: Cancer is becoming more common worldwide, affecting one third of the world’s population, and its morbidity and mortality are high. With the deep understanding of the cancer molecular biology, new cancer treatment programs continue to appear, and monoclonal antibody targeted drug therapy and immunotherapy have brought new hope to cancer patients. However, the lack of good models has hindered our understanding of tumor biology and the discovery of real drug targets. Effective in vitro tumor models are of great significance for the biological screening of anticancer drugs.
    OBJECTIVE: To summarize the application and prospect of induced pluripotent stem cells in tumor diseases.
    METHODS: PubMed, Web of Science and CNKI databases were searched for the articles concerning the induced pluripotent stem cells. The keywords were “induced pluripotent stem cells, tumor diseases, gene editing, regenerative medicine” in English and Chinese, respectively. After screening based on the inclusion and exclusion criteria, the articles with high relevance were included for review 
    RESULTS AND CONCLUSION:  Induced pluripotent stem cells have the advantages of wide sources, direct isolation from human peripheral blood, and being induced to differentiate into tumor tissues in vitro. Thus, more and more induced pluripotent stem cells for disease modeling and drug screening are being explored. With the continuous development of gene editing technology (CRISPER/Cas9), gene editing of stem cells has become possible to treat tumor diseases. 

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