Research hotspot of biological scaffold materials promoting osteogenic differentiation of bone marrow mesenchymal stem cells北大核心

BACKGROUND: At present, a single biological scaffold material is difficult to meet the osteogenic needs of bone tissue engineering, and bone marrow mesenchymal stem cells have excellent osteogenic characteristics. Composite scaffolds and scaffolds combined with growth factors have better osteogenic ability. It is a research hotspot at present. OBJECTIVE: To review different biological scaffolds and their modified scaffolds to promote the osteogenic differentiation of bone marrow mesenchymal stem cells. METHODS: The related articles published in CNKI, Wanfang, VIP, PubMed and Embase databases from January 2014 to July 2020 were searched by the first author with the keywords of “bone marrow mesenchymal stem cells, scaffolds, osteogenic differentiation, hydroxyapatite, collagen, chitosan” in English and Chinese. Finally, 69 articles were selected. RESULTS AND CONCLUSION: The rapid development of bone tissue engineering can effectively solve the problem of bone defect repair. Seed cells and biological scaffold materials are the core of bone tissue engineering. Bone marrow mesenchymal stem cells have excellent osteogenic differentiation ability and are widely used in bone tissue engineering. The combination of different scaffold materials, the use of advanced preparation technology, or the surface modification of scaffolds and the addition of growth factors can fully combine the advantages of various biological scaffold materials, induce the osteogenic differentiation of bone marrow mesenchymal stem cells and the formation of scaffold blood vessels, and achieve the purpose of repairing bone defects, and is the research focus of bone tissue engineering. © 2022, Publishing House of Chinese Journal of Tissue Engineering Research. All rights reserved.     

瘀胆血清诱导骨髓间充质干细胞向肝细胞的分化

BACKGROUND: Under certain conditions, bone marrow mesenchymal stem cells can be differentiated into hepatocytes, which are an important source of liver cells. Moreover, multiple factors can be involved in this induced differentiation process.OBJECTIVE: To investigate the inducible effect of cholestatic serum on the differentiation of bone marrow mesenchymal stem cells into hepatocytes.METHODS: Cholestatic animal model was prepared in rats to extract cholestatic serum. Bone marrow mesenchymal stem cells isolated from rats were divided into three groups and cultured in serum-free hepatocyte medium, serum-free hepatocyte medium plus cholestatic serum, serum-free hepatocyte medium plus normal serum, respectively.RESULTS AND CONCLUSION: The positive expression of alpha fetoprotein and keratin 18 and mass concentration of albumin were significantly higher in the serum-free hepatocyte medium plus cholestatic serum group than the other two groups (P < 0.05). These findings indicate that cholestatic serum has a certain inducible role in the differentiation of bone marrow mesenchymal stem cells into hepatocytes.  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     

低氧预处理诱导骨髓间充质干细胞Pim-1激酶高表达抑制细胞凋亡

BACKGROUND: Bone marrow mesenchymal stem cells have a low survival rate after implanted into the ischemic myocardium. However, hypoxia preconditioning (HPC) may enhance bone marrow mesenchymal stem cell proliferation and promote its survival rate. OBJECTIVE: To explore whether Pim-1 is involved in HPC protecting against apoptosis of bone marrow mesenchymal stem cells and the relevant mechanism. METHODS: Bone marrow mesenchymal stem cells were respectively subjected to HPC for 0, 6, 12, and 24 hours. The expression of Pim-1 and apoptosis-related genes were detected by RT-qPCR and western blot. Then, the best hypoxic preconditioning time was determined as 12 hours. Then, bone marrow mesenchymal stem cells were assigned to one of the following groups: control (without HPC), 12-hour HPC, 12-hour HPC+Pim-1 inhibitor groups. Flow cytometry analysis was used to detect the cell apoptosis, Transwell assay to analyze the cell migration ability in each group, and JC-1 kit to detect mitochondrial membrane potential. Animal models of myocardial infarction were established. One week after modeling, bone marrow mesenchymal stem cells were given via multi-point injection around the infarct zone of rats. Two weeks after modeling, heart tissues of rats were taken and sliced followed by DiI staining to calculate the survival rate of bone marrow mesenchymal stem cells. Additionally, rat cardiac function was assessed by echocardiography prior to and after modeling as well as at 4 weeks after cell transplantation. RESULTS AND CONCLUSION: At 12 hours after HPC, the expression of Pim-1, p-Akt and Bcl-2 gene in the infarct region was significantly increased, but the expression of caspase-3 and Bax was significantly decreased. Compared with the control group, cell viability in the 12-hour HPC group was increased very significantly at 1 week after cell transplantation (P < 0.001), the migration and anti-apoptosis ability were enhanced significantly (P < 0.01) and the cardiac function of rats was significantly improved in the 12-hour HPC group (P < 0.05). All of these protective effects were blocked by the Pim-1 inhibitor. These findings indicate that HPC can protect bone marrow mesenchymal stem cells from apoptosis through activating Akt and up-regulating Pim-1, and thereby improve the therapeutic effect of bone marrow mesenchymal stem cell transplantation on ischemic heart diseases. 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      

骨髓间充质干细胞移植后在胸腺内的定居

BACKGROUND: Bone marrow mesenchymal stem cells have low immunogenicity and can induce immune tolerance. At present, the mechanism of immune regulation of bone marrow mesenchymal stem cells is not completely understood. It has been rarely reported whether the bone marrow mesenchymal stem cells can migrate to the thymus after transplantation.OBJECTIVE: To observe the distribution and survival of bone marrow mesenchymal stem cells in the thymus of aging rats after transplantation.METHODS:Bone marrow mesenchymal stem cells cultured in vitro were transfected by adenovirus vectors expressing green fluorescent protein. Transfected bone marrow mesenchymal stem cells were injected into the portal vein of aging rats. At days 3, 7, 14, 21 after transplantation, the survival of bone marrow mesenchymal stem cells homing to the thymus was observed under fluorescence microscope. At day 3 after transplantation, thymus tissues were taken and stained with hematoxylin-eosin for pathological observation. RESULTS AND CONCLUSION:Green fluorescent protein-labeled bone marrow mesenchymal stem cells had a strong green fluorescence at days 3 and 7 after transplantation, and the cell contour was clear. There was no significant difference in the mean absorbance values at days 3 and 7 (P > 0.05). Expression of green fluorescent protein was weakened significantly at days 14 and 21 compared with that at day 3 (P < 0.05). At 3 days after transplantation, the transplanted bone marrow mesenchymal stem cells were clearly visible in the thymus, and acute rejection was not observed. The results show that bone marrow mesenchymal stem cells can migrate to the damaged thymus tissue through the blood circulation, and can survive at least 1 week.  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     

间充质干细胞对再生障碍性贫血患者造血支持及T淋巴细胞分泌功能的影响

BACKGROUND: Recently, the role of mesenchymal stem cells in aplastic anemia has been widely explored. However, its underlying mechanism remains unclearly.OBJECTIVE:To study the effect of umbilical cord blood and bone marrow mesenchymal stem cells on hematopoietic support and secretory function of T lymphocytes in patients with aplastic anemia.METHODS:Cord blood and bone marrow samples from 48 cases of aplastic anemia and 48 healthy lying-in women to isolate mesenchymal stem cells using flow cytometry. Mesenchymal stem cells from the cord blood and bone marrow were respectively co-cultured with cord blood mononuclear cells to count burst forming units-erythroid and colony forming units-granulocyte/macrophage. Mesenchymal stem cells were co-cultured with T lymphocytes from aplastic anemia patients undergoing phytohemagglutinin stimulation, and ELISA was used to detect interleukin-2, interleukin-4 and interferon-γ levels secreted from T lymphocytes.RESULTS AND CONCLUSION: The number of burst forming units-erythroid and colony forming units-granulocyte/macrophage significantly increased in normal bone marrow or umbilical cord blood mesenchymal stem cells co-cultured with cord blood mononuclear cells (P < 0.05), but reduced remarkably in umbilical cord blood mesenchymal stem cells from aplastic anemia patients co-cultured with cord blood mononuclear cells (P < 0.05). Levels of interleukin-2, interleukin-4 and interferon-γ from T lymphocytes were inhibited significantly after co-culture with normal bone marrow mesenchymal stem cells compared with phytohemagglutinin-induced T lymphocytes (P < 0.05). There was a similar inhibitory effect after co-culture with normal umbilical cord blood mesenchymal stem cells. There was a significantly reduction in the capacity of inhibiting interleukin-2, interleukin-4 and interferon-γ levels from T lymphocytes after co-culture with bone marrow mesenchymal stem cells from aplastic anemia patients (P < 0.05). Aplastic anemia patients show some functional defects in their bone marrow mesenchymal stem cells that have a weaker inhibitory role than normal bone marrow or umbilical cord blood mesenchymal stem cells in the hematopoietic support and secretory function of T lymphocytes. These findings indicate that mesenchymal stem cells from aplastic anemia patients can influence the pathological progress through weakening hematopoietic support and secretory function of T lymphocytes.  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     

骨组织工程中的间质干细胞：成骨活性、免疫特性、促血管化及成骨效应

BACKGROUND: It is still a challenge to repair bone defects caused by trauma, infection, tumor and congenital diseases. Bone tissue engineering is a promising method for bone defect repair showing important guiding significance in the clinic. OBJECTIVE: To review the progress of proliferation, osteogenic activity, immunogenicity, proangiogensis and in vivo osteogenic effect of mesenchymal stem cells in bone tissue engineering. METHODS: The first author retrieved Wanfang and PubMed datebase for literatures published from 2008 to 2016, using the keywords of “mesenchymal stem cell, tissue engineering, osteogenesis, immune property, angiogenesis” in Chinese and English, respectively. Articles regarding mesenchymal stem cells, tissue engineering, osteogenesis, immune property and angiogenesis were included, and repetitive and dated studies were excluded. Totally 1 772 articles were retrieved initially, and in accordance with inclusion and exclusion criteria, 41 eligible articles were included for review analysis. RESULTS AND CONCLUSION: Bone marrow mesenchymal stem cells and adipose-derived mesenchymal stem cells are extensively applied in bone tissue engineering. Studies have shown that the osteogenic activity of bone marrow mesenchymal stem cells is higher than that of adipose-derived mesenchymal stem cells, but its immune regulation effect is weaker than that of adipose-derived mesenchymal stem cells. Mesenchymal stem cells hold remarkable immune regulation (immunosuppression and immune enhancement) and tissue repair capacity, which can eliminate inflammatory reactions at injured sites, promoting tissue repair. Adipose-derived mesenchymal stem cells cultured under hypoxia environment can secret more angiogenic cytokines generating more vascular structures. Furthermore, increasing proof have confirmed that porous nano-polylactic acid combined with nano-carbon biological material can significantly promote the proliferation and osteogenesis of bone marrow mesenchymal stem cells. Taking its tumorigenesis into consideration, mesenchymal stem cells should be prudently used in the clinic. 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

同种异体来源骨髓间充质干细胞移植可改善衰老心脏的功能

BACKGROUND: Bone marrow mesenchymal stem cells can secrete a variety of factors in the local lesion, and these factors can promote cell proliferation and inhibit cell apoptosis. OBJECTIVE: To observe the curative effect of bone marrow mesenchymal stem cell transplantation on the aging heart of rats and to explore the possible mechanism of action. METHODS: Thirty Sprague-Dawley rats were randomized into three groups: normal blank group, model group and treatment group. Aging models were made in the latter two groups by injection of D-galactose. Rats in the treatment group were given allogeneic bone marrow mesenchymal stem cell injection, once a week, totally four times. At 1 week after final injection, the heart tissues were sliced into sections to observe the pathological changes using hematoxylin-eosin staining. Western blot assay was used to detect the expression of basic fibroblast growth factor in the heart tissues. Real-time PCR was used to measure the expression of p53 mRNA in the heart tissues. RESULTS AND CONCLUSION: Bone marrow mesenchymal stem cell transplantation could improve the pathological morphology of the aging heart. Compared with the model group, the expression of basic fibroblast growth factor in the heart tissues was significantly higher in the treatment group (P < 0.05), but the mRNA expression of p53 was lower (P < 0.05). It is speculated that bone marrow mesenchymal stem cells can interact with heart cells to secrete basic fibroblast growth factor and reduce p53 mRNA expression, thereby playing a curative effect on the aging heart.  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     

妇科养坤丸与骨髓间充质干细胞移植修复薄型子宫内膜

BACKGROUND: Studies have found that endometrial cells from bone marrow donors can be detected in the endometrium of female patients after bone marrow suppression.OBJECTIVE:To investigate the effect of Fukeyangkun pills combined with bone marrow mesenchymal stem cells (BMSCs) transplantation in the treatment of thin endometrium.METHODS: Thirty female rats at rutting period were randomized into control, model, Fukeyangkun pills, cell transplantation and combined group (n=6 per group). Rat models of thin endometrium were made in the latter five groups. Rats in the six groups were respectively subjected to routine feeding, tail vein injection of normal saline, tail vein injection of bone marrow mesenchymal stem cells (1 mL) at 6 hours and 10 days after modeling, intragastric administration of 5 mL/kg Fukeyangkun pill solution for continuous 20 days, or tail vein injection of bone marrow mesenchymal stem cells (1 mL) at 6 hours and 10 days after modeling plus intragastric administration of 10 mL/kg Fukeyangkun pill solution for continuous 20 days. At 21 days after modeling, hematoxylin-eosin staining was used to observe the morphological changes of the endometrical tissues and measure the endometrium thickness. The expression of cytokeratin and vimentin was determined by western blot assay.RESULTS AND CONCLUSION: Compared with the model group, the endometrium thickness and the expression of cytokeratin and vimentin (P < 0.05) were increased successively in the Fukeyangkun pills group, cell transplantation group, and combined group to different extents. Of these groups, the endometrium thickness and the expression of cytokeratin and vimentin in the combined group were the most close to normal levels. Our data demonstrate that bone marrow mesenchymal stem cell transplantation can induce regeneration of the endometrial cells and repair endometrial tissue. Furthermore, treatment of Fukeyangkun pills obviously augments the repair effect of bone marrow mesenchymal stem cell transplantation on thin endometrium.  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     

Biological characteristics and immunoregulation of exosomes derived from mesenchymal stem cells北大核心

BACKGROUND: Clarifying the synthesis and regulation of exosomes derived from mesenchymal stem cells is of great significance to the research and application of exosomes in the future. OBJECTIVE: To summarize the biological characteristics in exosomes derived from different mesenchymal stem cells and the role of these exosomes in the immune regulation, which hopes to find new breakthroughs in the study of exosomes in the future and provide ideas for cell-free therapy. METHODS: The articles were searched on PubMed, CNKI and Wanfang using the keywords of “stem cells, mesenchymal stem cells, exosomes, immunomodulation, inflammatory mediator, biological characteristics of exosomes, biological characteristics of mesenchymal stem cells, regeneration” in Chinese and English. Finally, 105 articles were included for review. RESULTS AND CONCLUSION: Mesenchymal stem cells are a type of pluripotent stem cells that exist widely in various tissues of the body. Mesenchymal stem cells not only have stem cell characteristics, but also play an important role in the immunosuppressive properties. Mesenchymal stem cells had been clinically applied for the treatment of many diseases. Therefore, mesenchymal stem cells were used to manage novel coronavirus pneumonia, and had ideal treatment effect. Exosomes are endosome-derived nanometer-scale vesicles (40–200 nm in diameter). Exosomes derived from mesenchymal stem cells have the same immune regulation function as its maternal cells, including that carrying immunosuppressive factors, promoting macrophages polarization into M2 type, preventing differentiation of pro-inflammatory T cell subsets and inhibiting antigen presentation. © 2022, Publishing House of Chinese Journal of Tissue Engineering Research. All rights reserved.     

骨髓间充质干细胞经尾静脉移植治疗肝纤维化

BACKGROUND: Liver fibrosis is the early stage of terminal liver diseases. Effective treatment for liver fibrosis can prevent the occurrence of terminal liver diseases. Bone marrow mesenchymal stem cell transplantation is a promising method to treat liver fibrosis. OBJECTIVE: To study the therapeutic effect of bone marrow mesenchymal stem cells on liver fibrosis in rats. METHODS: Eighteen Sprague-Dawely rats were randomized into three groups: control, model and cell transplantation groups. Animal models of carbon tetrachloride-induced liver fibrosis were made in the latter two groups. After modeling, 1 mL bone marrow mesenchymal stem cells (5×105) or the same volume of normal saline was injected via the tail vein into the rats in the cell transplantation and model groups, respectively. Rats in the control group were given no treatment. Degree of liver fibrosis, liver function, histological changes of the liver were detected and observed in the three groups at 4 weeks after treatment. RESULTS AND CONCLUSION: In the control group, the liver tissues had normal structure with no fibrosis; in the model group, proliferation of fibrous tissues in the portal area of the liver, inflammatory cell infiltration, vacuolar degeneration and irregular arrangement of liver cells, and tissue structure damage were observed; in the transplantation group, liver tissue damage was severer than the control group but milder than the model group. Levels of serum hyaluronidase, type IV collagen and procollagen III were significantly lower in the cell transplantation group than the model group (P < 0.05). These findings indicate that bone marrow mesenchymal stem cell transplantation can alleviate liver fibrosis and improve liver function in rats with carbon tetrachloride-induced liver fibrosis.  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