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    03 December 2014, Volume 18 Issue 50 Previous Issue    Next Issue
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    In vitro osteogenic induction of bone marrow mesenchymal stem cells after co-transfection with Ad-hBMP-2 and Ad-hTGF-β1
    Chen Jian-ping, Qiu Jun-qin, Zeng Zhao-xun, Chen Zong-xiong, Yin Cheng-hui
    2014, 18 (50):  8037-8041.  doi: 10.3969/j.issn.2095-4344.2014.50.001
    Abstract ( 261 )   PDF (654KB) ( 537 )   Save

    BACKGROUND: Advances in recombinant DNA technology provide a huge impetus to the development of bone tissue engineering research, which used for tissue-engineered bone construction can significantly improve the quality and efficiency of bone repair.
    OBJECTIVE: To evaluate the in vitro osteogenic induction of Ad-hBMP-2 and Ad-hTGF-β1 co-transfected bone marrow mesenchymal stem cells and to elucidate their relationship in bone formation.
    METHODS: Bone marrow mesenchymal stem cells from Sprague-Dawley rats were infected by high-titer recombinant adenoviruses carrying transforming growth factor-β1 and bone morphogenetic protein-2 genes, and then transfected cells were induced by exogenous genes detected with RT-PCR, ELISA, MTT and alkaline phosphatase test.
    RESULTS AND CONCLUSION: Adenovirus-infected bone marrow mesenchymal stem cells could express exogenous genes detected by RT-PCR. MTT test and alkaline phosphatase test showed the proliferation ability of co-transfected bone marrow mesenchymal stem cells was the strongest and the alkaline phosphatase activity was the highest. It has been observed that bone marrow mesenchymal stem cells co-transfected with Ad-hBMP-2 and Ad-hTGF-β1 can be induced to form bone tissue cooperatively and synergistically.


    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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    Isolation and culture of rat bone marrow mesenchymal stem cells: passage 3 cells exhibit rapid proliferation and high purity
    Zeng Zhi-mou, Fan Zhong-cheng, Zhang Shou, Liu Yi-heng, Wu Duo-qing, Wang Cong-ren
    2014, 18 (50):  8042-8047.  doi: 10.3969/j.issn.2095-4344.2014.50.002
    Abstract ( 247 )   PDF (858KB) ( 455 )   Save

    BACKGROUND: The first step of tissue engineering research is to produce a large number of seed cells with good biological activity, fast proliferation and high purity.
    OBJECTIVE: To explore the biological characteristics of rat bone marrow mesenchymal stem cells isolated and cultured by the whole bone marrow adherence method.
    METHODS: Rat bone marrow mesenchymal stem cells were isolated and cultured, and then passage 3 cells were enrolled to draw a cell growth curve. Morphological changes of cells at different passages were observed. Cells in passage 2 and passage 3 were characterized by their surface marker expressions of CD29, CD90, CD34 and CD45.
    RESULTS AND CONCLUSION: Bone marrow mesenchymal stem cells at passages 1-3 exhibit classic morphology of fibroblast-like cells and presented plastic-adherent property. Phenotypes of P2 generation were detailed as: expressions of CD29, CD90, CD34, CD45 were 91.5%, 96.2%, 1.3%, and 8.0%, respectively. Phenotypes of passage 3 cells were detailed as: expressions of CD29, CD90, CD34, CD45 were 98.2%, 98.1%, 0.6%, 2.0%, respectively. The cell growth curve indicated the cell proliferation reached the peak at an inoculation 
    concentration of 8×107/L. Overall, bone marrow mesenchymal stem cells at passage 3 with good viability, rapid proliferation and high purity can be used as seed cells for tissue engineering research.


    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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    Recombinant adeno-associated virus type 9 transfection of mouse bone marrow mesenchymal stem cells
    Dong Shuo, Huang Ying, Ma Yi-tong, Meng Lin-lin, Liu Fen, Chen Bang-dang, Chen Xiao-cui
    2014, 18 (50):  8048-8053.  doi: 10.3969/j.issn.2095-4344.2014.50.003
    Abstract ( 240 )   PDF (1890KB) ( 334 )   Save

    BACKGROUND: Recombinant adeno-associated virus type 9 (rAAV9) has a good affinity to myocardialcytes, and it is an ideal carrier for gene therapy of myocardial infarction.
    OBJECTIVE: To investigate the transfection efficiency of rAAV9-enhanced green fluorescence protein (eGFP) in transfection of mouse bone marrow mesenchymal stem cells.
    METHODS: rAAV9-eGFP was transfected into mouse bone marrow mesenchymal stem cells which were subcultured to the fourth generation at different multiplicities of infection (MOI=1×105, 1×106, 1×107). To find the best condition of transfection, we observed the eGFP expression under the inverted fluorescence microscope at 1-7 days after transfection. Then the transfection efficiency of rAAV9-eGFP under the optimal MOI was determined by flow cytometry.
    RESULTS AND CONCLUSION: The cells with rAAV9-eGFP transfection at MOl of 1×107 began to exhibit eGFP expression at the 1st day after transfection, and the cells transfected at MOI of 1×105 and 1×106 began to exhibit eGFP expression from the 2nd day after transfection. The eGFP expression increased with the MOI used for transfection, and the intensity of eGFP expression increased with the time going on. At the 5th day, the eGFP 
    expression reached the peak value, and meanwhile, the transfection efficiency at MOI=1×107 was about 8%. rAAV9-eGFP cannot transfect mouse bone marrow mesenchymal stem cells effectively.


    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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    Cotransfection of sox9 and LMP1 genes in rabbit bone mesenchymal stem cells through lentivirus vectors in vitro
    Liu Wei, Wang Jie, Xing Yong-ming, Li Chun-zhi, Chen Chang-wei, Zhao Hong, Gong De-jun
    2014, 18 (50):  8054-8060.  doi: 10.3969/j.issn.2095-4344.2014.50.004
    Abstract ( 313 )   PDF (2512KB) ( 360 )   Save

    BACKGROUND: Compared with the traditional method of cytokines, gene transfection into a host cell by lentivirus can achieve a sustained long-term efficient expression. Double/multiple gene co-modification therapy is superior to single gene therapy to induce the differentiation of bone marrow mesenchymal stem cells into nucleus pulposus-like cells.
    OBJECTIVE: To build two recombinant lentivirus vectors separately expressing sox9 and LMP1 genes, and then co-transfect rabbit bone marrow mesenchymal stem cells for observing the expression of sox9 and LMP1 genes.
    METHODS: Double enzyme digestion was performed for plasmid 13abiv6c_1366933 containing sox9 gene sequences provided by GeneArt, and the sox9 gene was cloned into pLenti6.3_MCS_IRES2-EGFP carrier to harvest the plasmid pLMIG-13GS0345-1 including sox9 gene. Through single oligo design and synthesis of LMP1 gene sequences that were cloned into pLenti6.3_MCS_IRES2 DsRed-Monomer carrier, the plasmid gs0318 13-1 including LMP1 gene was obtained. The plasmids were packed by 293T cells to obtain the recombinant lentivirus vector carrying sox9 gene marked by green fluorescent protein markers (Lenti-SOX9-GFP) and the recombinant lentivirus vector carrying LMP1 gene marked by red fluorescent protein markers (Lenti-LMP1-RFP). The Lenti-SOX9-GFP and Lenti-LMP1-RFP were co-transfected into rabbit bone marrow mesenchymal stem cells to observe the expression of sox9 and LMP1 genes.
    RESULTS AND CONCLUSION: Sequencing results showed that the insert sequences of plasmids pLMIG-13GS0345-1 and 13GS0318-1 were completely consistent with the sox9 gene (NM_000346) and LMP1 gene (AF345904.1) sequences in the Genbank respectively, indicating that the Lenti-SOX9-GFP and Lenti-LMP1-RFP were successfully constructed. The expression of green fluorescent protein and red fluorescent protein could be observed in the same view after co-transfection of rabbit bone marrow mesenchymal stem cells by Lenti-SOX9-GFP and Lenti-LMP1-RFP. The RT-PCR and western blot assay results also proved that the Lenti-SOX9-GFP and Lenti-LMP1-RFP could successfully and efficiently co-transfect the bone marrow mesenchymal stem cells, and mRNA and protein expressions of SOX9 and LMP1 gene could be successfully observed. The recombinant lentivirus vectors Lenti-SOX9-GFP and Lenti-LMP1-RFP were successfully constructed and successfully co-expressed in the rabbit bone marrow mesenchymal stem cells, which provided preliminary experimental basis for further research in nucleus pulposus tissue engineering.


    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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    Schwann cells induce the differentiation of neuregulin-1-transfected bone marrow stromal stem cells into neuron-like cells
    Ding Dong, Liang Jun, Zhang Ji-fei
    2014, 18 (50):  8061-8065.  doi: 10.3969/j.issn.2095-4344.2014.50.005
    Abstract ( 229 )   PDF (1866KB) ( 436 )   Save

    BACKGROUND: Bone marrow stromal stem cells have been successfully induced by chemical method or co-cultured with Schwann cells to differentiate into Schwann cell-like cells, but there are still some drawbacks. The former has some toxicity to cells, and the latter can take a long time for cell induction.
    OBJECTIVE: To explore the feasibility that Schwann cell medium induces the neuronal differentiation of neuregulin-1-transfected bone marrow stromal stem cells.
    METHODS: Neuregulin-1 was used to transfected bone marrow stromal cells. When the cells were at stable state, the culture medium was replaced by Schwann cell medium, placed at a 37 ℃, 5% CO2 incubator.
    RESULTS AND CONCLUSION: After 10 days of induced culture in Schwann cell conditioned medium, neuregulin-1-transfected cells were retracted in a fusiform shape under light microscope, and there were Schwann cell-like cells that were closely arranged in a island-like shape. Results from immunofluorescence staining showed that induced bone marrow stromal cells were positive for S-100, neuron-specific enolase and glial fibrillary acidic protein, and the positive rates were 35.99%, 25.32% and 38.69%, respectively. Experimental findings suggest that the Schwann cells-secreted cytokines and neuregulin-1 protein can co-induce the differentiation of bone marrow stromal stem cells efficiently into nerve cells that express the surface antigens of Schwann cells, neurons and glial cells.


    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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    Isolation, cultivation and identification of porcine bone marrow mesenchymal stem cells using Ficoll density gradient centrifugation method
    Liu Chuan-bin, Lǚ Shuang-hong, Zhang Xiao-zhong
    2014, 18 (50):  8066-8071.  doi: 10.3969/j.issn.2095-4344.2014.50.006
    Abstract ( 322 )   PDF (2068KB) ( 647 )   Save

    BACKGROUND: Culture condition, isolation method and efficiency of porcine bone marrow mesenchymal stem cells are different, and there is a lack of unified identification standards.
    OBJECTIVE: To establish a high-efficiency and economical method of isolating, culturing and identifying porcine bone marrow mesenchymal stem cells.
    METHODS: The bone marrow was collected from healthy porcine femur to isolate mononuclear cells by Ficoll density gradient centrifugation method. After primary and subculture, the cell surface antigens were detected by flow cytometery, and the osteogenic, adipogenic and chondrogenic differentiation abilities of the cells were observed.
    RESULTS AND CONCLUSION: The isolated mononuclear cells showed exuberant viability, and grew well in vitro. They were spindle- or small polygonal-shaped and had a stable doubling time on culture. Flow cytometric analysis revealed that they were positive for CD29, CD44, CD90, and negative for CD14, CD34, CD45, CD166, HLA-DR. Furthermore, they were able to differentiate into osteogenic, adipogenic and chondrogenic lineages under specific conditions in vitro. Porcine bone marrow mesenchymal stem cells isolated by Ficoll density gradient centrifugation method can be purified, grow well in vitro, and have multi-lineage differentiation potentials, which can act as seed cells for tissue engineering research.


    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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    Different concentrations of angiotensin II induce directional differentiation of bone marrow mesenchymal stem cells into cardiomyocytes
    Shi Jing-bao, Xing Wan-hong
    2014, 18 (50):  8072-8079.  doi: 10.3969/j.issn.2095-4344.2014.50.007
    Abstract ( 327 )   PDF (2668KB) ( 362 )   Save

    BACKGROUND: There are less experimental studies addressing angiotensin II-induced differentiation of bone marrow mesenchymal stem cells into cardiomyocytes, and there is no uniform standard for this new inducer used in the experiments, so the results of the induced experimental studies are certainly different.
    OBJECTIVE: To discuss the optimal concentration of angiotensin II to induce the differentiation of bone marrow mesenchymal stem cells into cardiomyocytes.
    METHODS: Bone marrow mesenchymal stem cells from rats were isolated, cultured and purified by the density gradient centrifugation combined with adherence method. Passage 3 cells were divided into four induction groups (0.05, 0.1, 0.2, 0.5 μmol/L angiotensin II) and a control group. In the four induction groups, the corresponding inducer was added 24 hours after cells were seeded, and after 24 hours of induction, the cells were cultured in complete medium for 4 weeks. Cells in the control group were only cultured in the complete medium. MTT assay was used to detect the absorbance values at days 1, 3, 5, 7 to calculate the cell proliferation inhibition rate in each group. Expression of cardiac-specific cTnT and β-MHC in bone marrow mesenchymal stem cells was detected by immuno?uorescence staining at 1 and 4 weeks after induction. mRNA expression of cardiac-transcription-factor GATA4 and NKx2.5 in bone marrow mesenchymal stem cells was measured by real-time PCR at 4 weeks after induction.
    RESULTS AND CONCLUSION: The cell proliferation curves were similar among different groups. The cell proliferation inhibition rate in the 0.05 μmol/L group began to appear negative, which was significantly different from the other groups at the 5th day (P < 0.05). The cell proliferation inhibition rate of 0.1 μmol/L group was significantly lower than that of 0.2 or 0.5 μmol/L groups at the 5th and 7th days. cTnT and β-MHC were detected in the bone marrow mesenchymal stem cells of four induction groups, but the control group was negative for cTnT and β-MHC. After 1 week of induction, the positive rates of cTnT and β-MHC in the 0.5 μmol/L group was significantly higher than that in the 0.05 μmol/L group (P < 0.05). After 4 weeks of induction, the positive rates of cTnT and β-MHC had no difference between the 0.1 μmol/L and
    0.2 μmol/L groups (P > 0.05). The early cardiac transcription factor GATA-4 and NKx2.5 were detected by RT-PCR in the cells of four induction groups after 4 weeks of induction, while their expression was negative in the control group. These findings suggest that after angiotensin II induction, bone marrow mesenchymal stem cells can express the cardiac-specific protein cTnT, β-MHC and transcription factor GATA-4 and NKx2.5. As mentioned above, the suitable concentration of angiotensin II is 0.1 μmol/L.


    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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    Damage of chemotherapy agents to bone marrow mesenchymal stem cells
    Wang Jin-huan, Wang Zhen-ling, Wang Xiao-fang, Zhao Zhi-gang
    2014, 18 (50):  8080-8087.  doi: 10.3969/j.issn.2095-4344.2014.50.008
    Abstract ( 372 )   PDF (908KB) ( 655 )   Save

    BACKGROUND: Many chemotherapy drugs can produce adverse reactions, such as bone marrow suppression, when they kill tumor cells. It cannot only damage hematopoietic cells, but also damage bone marrow mesenchymal stem cells. To understand the role of various chemotherapy agents on bone marrow mesenchymal stem cells is conductive to rational choice of chemotherapy drugs as well as achievement of high-efficiency, low-toxicity, clinical efficacy.
    OBJECTIVE: To investigate the changes in proliferation, differentiation and hematopoiesis support ability of bone marrow mesenchymal stem cells after exposure to chemotherapy agents.
    METHODS: Mesenchymal stem cells were isolated from normal adult bone marrow and cultured in media with different chemotherapy agents (cyclophosphamide, busulfan, cytarabine, daunorubicin, vincristine, etoposide, methotrexate, dexamethasone). After exposure to chemotherapeutic agents, the changes of cell proliferation, 
    apoptosis and recovery ability were detected. In vitro drug-treated bone marrow mesenchymal stem cells differentiated into adipocytes and osteocytes, identified by oil red O and Von Kossa staining. RT-PCR method was used to detect the expression of hematopoietic cytokines in bone marrow mesenchymal stem cells after drug treatment. Colony formation assay was used to detect the hematopoiesis support ability of bone marrow mesenchymal stem cells after drug treatment.
    RESULTS AND CONCLUSION: Bone marrow mesenchymal stem cells were resistant to three agents: cyclophosphamide, busulfan and methotrexate, and other agents could induce apoptosis of bone marrow mesenchymal stem cells and reduce the proliferation of bone marrow mesenchymal stem cells. However, bone marrow mesenchymal stem cells recovered after withdrawal of vincristine and dexamethasone. Bone marrow mesenchymal stem cells, after exposure to chemotherapy agents, still had the ability of multi-directional differentiation, which could differentiate into adipocytes and osteoblasts in vitro. Moreover, chemotherapy agent-treated bone marrow mesenchymal stem cells could express hematopoietic cytokines (stem cell factor, monocyte colony stimulating factor, interleukin-6 and granulocyte colony-stimulating factor) and possessed hematopoietic supportive ability. But, after exposure to daunorubicin, vincristine, etoposide, and cytarabine, bone marrow mesenchymal stem cells showed limited proliferation capacity and impaired haematopoiesis support ability. These findings demonstrate that chemotherapy agents commonly used clinically (daunorubicin, vincristine, etoposide, and cytarabine) can impact the proliferation and hematopoiesis supportabilities of bone marrow mesenchymal stem cells, but these agents cannot affect the multi-directional differentiation ability and expression of hematopoietic cytokines of bone marrow mesenchymal stem cells. Moreover, several chemotherapy agents have no effects on biological characteristics of bone marrow mesenchymal stem cells, such as cyclophosphamide, busulfan and methotrexate.


    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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    Effect of dexmedetomidine on neuronal differentiation of umbilical cord blood mesenchymal stem cells
    Fan Zhi-gang, Qiao Lei
    2014, 18 (50):  8088-8092. 
    Abstract ( 225 )   PDF (706KB) ( 448 )   Save

    BACKGROUND: Increasing evidence has shown that dexmedetomidine has a significant neuroprotection against ischemia-reperfusion injury, but its mechanism of action on the nervous system and its pathways to affect nerve cell function are rarely reported.
    OBJECTIVE: To study the effect of dexmedetomidine on proliferation and neuronal differentiation of umbilical cord blood mesenchymal stem cells.
    METHODS: Umbilical cord blood mesenchymal stem cells at passage 3 were divided into control, low-concentration (1 μg/L) and high-concentration (10 μg/L) dexmedetomidine groups. MTT was used to detect the viability of umbilical cord blood mesenchymal stem cells; western blot assay was used to determine the ERK1/2 phosphorylation in the cells; immunofluorescence staining was used to detect the percentage of NeuN/DAPI, GFAP/DAPI and Nestin/DAPI positive cells. Cell differentiation and proliferation abilities were observed.
    RESULTS AND CONCLUSION: Cell viability and EKR1/2 phosphorylation level were significantly increased in the low-concentration group compared to the control group (P < 0.05); while these two indicators in the high-concentration group were significantly lower than those in the other two groups (P < 0.05). The number of NeuN and GFAP positive cells was increased significantly in the two dexmedetomidine groups compared with the control group (P < 0.05), while the number of Nestin positive cells was significantly decreased in the two 
    dexmedetomidine groups (P < 0.05). These findings indicate that low-concentration dexmedetomidine can induce the proliferation of umbilical cord blood mesenchymal stem cells that is however inhibited by the high-concentration dexmedetomidine, which can be realized by regulating EKR1/2 phosphorylation level. In addition, low- and high-concentration dexmedetomidine can both induce the neuronal differentiation of umbilical cord blood mesenchymal stem cells.


    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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    Treatment of chronic graft-versus-host disease with human umbilical cord mesenchymal stem cells
    Huang Ying-dan, Xiao Cui-rong, Lin Jin-zong, Hong Xiu-li, Hu Jia-sheng, Lu Quan-yi
    2014, 18 (50):  8093-8097.  doi: 10.3969/j.issn.2095-4344.2014.50.010
    Abstract ( 299 )   PDF (628KB) ( 565 )   Save

    BACKGROUND: Mesenchymal stem cells have immunomodulatory effects, which have been proven to be successful in treating acute graft-versus-host disease. However, there are fewer reports concerning human umbilical cord mesenchymal stem cells in treating chronic graft-versus-host disease, particularly for lung-type chronic graft-versus-host disease.
    OBJECTIVE: To evaluate the effect of human umbilical cord mesenchymal stem cells to treat chronic graft-versus-host disease after hematopoietic stem cell transplantation.
    METHODS: Ten patients undergoing allo-hematopoietic stem cell treatment were clearly diagnosed as having chronic graft-versus-host disease, and had no improvement after conventional immunosuppressive therapy. These patients received the treatment of human umbilical cord mesenchymal stem cells, 2×107 cells per curative unit, 1-2 units every two weeks. The therapeutic results were evaluated according to the clinical standards.
    RESULTS AND CONCLUSION: In four patients with lung-type chronic graft-versus-host disease, three patients were effective. In two patients with skin-type chronic graft-versus-host disease, one patient had progress, and another one was effective. In four patients of liver rejection, two patients were effective and the other two were ineffective. The total effective rate was 70% (7/10). Human umbilical cord mesenchymal stem cell infusion can be effective to refractory chronic graft-versus-host disease.


    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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    Umbilical cord blood stem cell transplantation influences the endothelium-dependent vasodilation in type 2 diabetic patients with lower extremity vascular disease
    Li Cui-fang, Yao Yuan
    2014, 18 (50):  8098-8102.  doi: 10.3969/j.issn.2095-4344.2014.50.011
    Abstract ( 275 )   PDF (704KB) ( 505 )   Save

    BACKGROUND: Studies have shown that under certain conditions stem cells can be induced to differentiate into vascular endothelial cells, promoting local angiogenesis, generating the new capillary network, and enriching the collateral circulation, so as to improve lower limb ischemia.
    OBJECTIVE: To explore the effects of umbilical cord blood stem cell transplantation on endothelium-dependent vasodilation of type 2 diabetic patients with lower extremity vascular disease.
    METHODS: Totally 100 type 2 diabetic patients with lower extremity vascular disease were enrolled and divided into two groups: experimental group (n=60) and control group (n=40). The experimental group adopted the intravenous injection of umbilical cord blood stem cells, while the control group was subject to normal saline infusion. After 4 weeks, basic indexes and endothelium-dependent vasodilation were compared between two groups. 
    RESULTS AND CONCLUSION: In the experimental group, fasting blood glucose, 2-hour postprandial blood glucose, glycosylated hemoglobin, cholesterol, triglyceride levels were significantly reduced (P < 0.05), while fasting insulin, 2-hour postprandial insulin, vascular endothelial dilation function were significantly increased after treatment (P < 0.05). In the control group, there were no differences in fasting blood glucose, 2-hour postprandial blood glucose, glycosylated hemoglobin, cholesterol, triglyceride levels before and after treatment (P > 0.05). These findings indicate that umbilical cord blood stem cell transplantation can improve the endothelial function and promote the collateral circulation in type 2 diabetic patients with vascular lesions of lower extremities, thereby to avoid the occurrence of diabetic foot.


    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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    Transplantation of human umbilical cord blood mononuclear cells for treatment of myocardial infarction with heart failure
    Yu Le, Zhang Ming
    2014, 18 (50):  8103-8107.  doi: 10.3969/j.issn.2095-4344.2014.50.012
    Abstract ( 241 )   PDF (313KB) ( 557 )   Save

    BACKGROUND: Increasing basic researches have confirmed that human umbilical cord blood stem cells is safe and effective to treat acute myocardial infarction complicated by heart failure, but this method is not yet available for clinical use.
    OBJECTIVE: To observe the long-term effect of human umbilical cord blood mononuclear cell transplantation in the treatment of myocardial infarction combined with heart failure.
    METHODS: Twenty-five patients with myocardial infarction and heart failure admitted in the Department of Cardiology, Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, from January 2009 to June 2011 were randomly assigned to receive intracoronary transplantation of human umbilical cord blood mononuclear cells in addition to conventional therapy (transplantation group, n=12) or standard therapy (control group, n=13). All patients underwent standardized drug therapy, and coronary angiography and percutaneous coronary intervention were performed at acute phase. Improvement in heart function, left ventricular ejection fraction, left ventricular end-systolic volume and left ventricular end-diastolic volume at baseline and 12, 24 months after treatment were monitored.
    RESULTS AND CONCLUSION: The left ventricular ejection fraction, left ventricular end-systolic volume and left ventricular end-diastolic volume were significantly improved 12, 24 months after human umbilical cord blood stem cell transplantation compared to baseline (P < 0.05), while these parameters remained unchanged in the control group (P > 0.05). Compared with the control group, the left ventricular ejection fraction was increased significantly, and the left ventricular end-systolic volume and left ventricular end-diastolic volume were reduced significantly in the transplantation group. During the follow-up, no side effects were observed. These findings indicate that human umbilical cord blood mononuclear cell transplantation leads to significant and longstanding improvements in left ventricular performance of patients with myocardial infarction and heart failure.


    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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    Bone mesenchymal stem cell sheet transplantation combined with autologous iliac bone for repair of alveolar cleft
    Shen Yue, Ma Hai-ying, Zhang Yan-sheng, Wang Juan, Shi Bing-zheng
    2014, 18 (50):  8108-8112.  doi: 10.3969/j.issn.2095-4344.2014.50.013
    Abstract ( 214 )   PDF (628KB) ( 520 )   Save

    BACKGROUND: Autogenous iliac bone graft for repair of alveolar cleft often cannot achieve a stable therapeutic effect, and the graft resorption rate varies with each individual that is influenced by many factors.
    OBJECTIVE: To observe the bone resorption after bone marrow mesenchymal stem cell sheet transplantation with autogenous iliac cancellous bone for alveolar cleft repair.
    METHODS: Bilateral alveolar cleft models were prepared in dogs. Using the self-control method, bone marrow mesenchymal stem cell sheet combined with autogenous iliac bone (experimental group) and autogenous iliac bone alone (control group) were respectively implanted into the bilateral alveolar clefts. Mandible CT and microCT were used to compare the bone resorption rate, bone volume fraction, trabecular thickness, trabecular separation, and bone mineral density.
    RESULTS AND CONCLUSION: The bone resorption rate was significantly lower in the experimental group than the control group at 3 and 6 postoperative months (P < 0.01); while, the bone volume fracture and bone mineral density of the experimental group were significantly higher than those in the control group at postoperative 6 months (P < 0.05), but the trabecular separation of the experimental group was significantly lower than that in the control group (P < 0.05). In addition, there was no difference in the trabecular thickness between the two groups (P > 0.05). These findings indicate that bone marrow mesenchymal stem cell sheet transplantation combined with autogenous iliac bone graft can reduce bone resorption rate and meanwhile, promote new bone formation.


    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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    Effects of bone marrow mesenchymal stem cell transplantation on colon anastomotic healing
    Feng Tao, Zhao Xin, Xu Xing-wei, Zheng Peng, Kao Xiao-ming, Ji Wu
    2014, 18 (50):  8113-8121.  doi: 10.3969/j.issn.2095-4344.2014.50.014
    Abstract ( 197 )   PDF (6359KB) ( 341 )   Save

    BACKGROUND: With the advantage of strong proliferation ability, multi-directional differentiation potential, fully repair of damaged tissue, low immunogenicity and immune regulation, bone marrow mesenchymal stem cells can be used to treat refractory diseases which are difficult to cure by the traditional methods. Its immeasurable clinical application value makes it the new hot spots of cell transplantation therapy.
    OBJECTIVE: To observe the colonization of bone marrow mesenchymal stem cells in intestinal submucosa and healing effects after local injecting bone marrow mesenchymal stem cells into rat models of ischemic colon anastomosis. 
    METHODS: Forty female Sprague-Dawley rats were randomly divided into four groups: group A (postoperative 4 days, control group), group B (postoperative 7 days, control group), group C (postoperative 4 days, bone marrow mesenchymal stem cells group), group C (postoperative 7 days, bone marrow mesenchymal stem cells group). In group A and group B, 0.5 mL fetal bovine serum was injected into the line of the left colon ischemic bowel mucosa after anastomosis. Similarly, about 1×107 cells suspended in 0.5 mL sterile physical serum were submucosally injected into the left colon ischemic bowel mucosa in group C and group D. Rat anastomotic bursting pressure and hydroxyproline content were detected respectively. The migration and engraftment of donor derived bone marrow mesenchymal stem cells was detected by Y chromosome in situ hybridization in colon tissue. Histopathological observation was scored though hematoxylin-eosin and Masson staining.
    RESULTS AND CONCLUSION: Bone marrow mesenchymal stem cells transplantation augmented bursting pressure and hydroxyproline content at the site of ischemic colonic anastomosis. The histopathological features, except for the epithelization and inflammation, were significantly more favorable in the bone marrow mesenchymal stem cell groups, and the microvascular density was significantly higher than that in the control groups. These findings indicate that allogeneic bone marrow mesenchymal stem cells can be colonized in the receptor of ischemic colon anastomosis model, and significantly accelerate the recovery of ischemic colonic anastomosis. It contributes to the healing of ischemic colonic anastomosis through the paracrine activities of bone marrow mesenchymal stem cells, rather than direct differentiation.


    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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    Bone marrow mesenchymal stem cell transplantation in the treatment of rat radiation-induced lung injury
    Zheng Kai, Zhao Xing-wang, Wu Wei-zhen, Tan Jian-ming, Yang Shun-liang
    2014, 18 (50):  8122-8129.  doi: 10.3969/j.issn.2095-4344.2014.50.015
    Abstract ( 259 )   PDF (2932KB) ( 439 )   Save

    BACKGROUND: Except for corticosteroids and antibiotics, there is no effective treatment for radiation-induced lung injury. Recent studies have shown that bone marrow mesenchymal stem cells appear to have strong tissue repair ability.
    OBJECTIVE: To observe the therapeutic effect of bone marrow mesenchymal stem cells on radiation-induced lung injury in rats, and then to preliminarily explore the mechanism of action.
    METHODS: Bone marrow mesenchymal stem cells from male Sprague-Dawley rats were isolated, cultured and  
    identified in vitro. Sixty male Sprague-Dawley rats were subject to chest irradiation to establish radiation-induced lung injury models. Then, the model rats were randomly divided into treatment group and control group, respectively treated with tail vein injection of 2×109/L bone marrow mesenchymal stem cells and the same volume of normal saline. After 1, 2, 4, 6 weeks of irradiation, relevant parameters were detected. 
    RESULTS AND CONCLUSION: After 1, 2, 4 weeks of irradiation, the lung coefficient was significantly lower in the treatment group than the control group (P < 0.05). Under the microscope, less inflammatory exudation was from lung tissue in the treatment group, and the alveoli and alveolar wall structure were basically complete. The degree of fibrosis was significantly milder in the treatment group than the control group. Compared with the control group, the levels of serum transforming growth factor β1 and hydroxyproline were significantly lower in the treatment group (P < 0.05) at 2 weeks of irradiation, the activity of superoxide dismutase in lung tissue was significantly higher in the treatment group
    (P < 0.05) at 2, 4, 6 weeks of irradiation, the content of malondialdehyde was significantly lower in the treatment group
    (P < 0.05) at 4 and 6 weeks of irradiation, and the expression of pulmonary surfactant B was significantly higher in the treatment group at 6 weeks of irradiation. PCR results showed that Sry expressed in the lung, liver, pancreas, kidneys in varying degrees, especially obviously in the lung. These findings indicate that bone marrow mesenchymal stem cells can migrate into the radiation-injured lung tissue, to promote repair of radiation-induced lung injury. The treatment mechanism may be to lesser lung tissue fibrosis by inhibiting inflammation and antioxidation.


    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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    Hippocampus transplantation of bone marrow mesenchymal stem cells improves the memory function of Alzheimer’s disease rats
    Wang Zhuo, Ren Xiang-qian, Wei Dong-xing
    2014, 18 (50):  8130-8134.  doi: 10.3969/j.issn.2095-4344.2014.50.016
    Abstract ( 250 )   PDF (792KB) ( 665 )   Save

    BACKGROUND: Although medications can reduce and delay the progression of Alzheimer’s disease to a certain extent, but the effect is not obvious. Therefore, cell replacement therapy is a new attempt and exploration for the treatment of Alzheimer’s disease.
    OBJECTIVE: To study the improvement in learning and memory abilities of rats with Alzheimer’s disease after transplantation of bone marrow mesenchymal stem cells.
    METHODS: Alzheimer’s disease model was induced by injecting beta-amyloid 1-40 protein into the bilateral hippocampi. The bone marrow mesenchymal stem cells were then implanted into the hippocampus. After 4 weeks, the spatial cognition and memory ability of rats were evaluated with Morris water maze. BrdU and NF, GFAP immunofluorescence double-staining was adopted to test the differentiation and survival of implanted bone marrow mesenchymal stem cells. Western blot and immunohistochemistry methods were used to detect the expression of beta-amyloid protein in the cortex and hippocampus.
    RESULTS AND CONCLUSION: Compared with the model group, the escape latency of hidden platform was shortened significantly in the stem cell transplantation group (P < 0.01), while the number of crossing the platform was increased significantly (P < 0.05). The BrdU/NSE and BrdU/GFAP double staining positive cells could be found around the bilateral hippocampi. Western blot result showed the beta-amyloid protein expression decreased obviously after transplantation of bone marrow mesenchymal stem cells (P < 0.05). These findings indicate that transplanted bone marrow mesenchymal stem cells can survive and differentiate in the brain of rats, which can improve the learning and memory abilities of Alzheimer’s disease rats.


    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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    Treatment of early osteonecrosis of the femoral head with debridement, bone grafting and bone marrow mononuclear cells transplantation: functional evaluation of the hip joint
    Hu Qin, Yin Zong-sheng, Lu Ming, Zhang Hui, Ma Zhi-xiang
    2014, 18 (50):  8135-8139.  doi: 10.3969/j.issn.2095-4344.2014.50.017
    Abstract ( 295 )   PDF (756KB) ( 395 )   Save

    BACKGROUND: Several studies have indicated that reduced number and viability of bone marrow stem cells is closely related to the pathogenesis of osteonecrosis. Therefore, a sufficient number of transplanted bone marrow stem cells are more conducive to the reconstruction of necrotic area.
    OBJECTIVE: To analyze the clinical effect of debridement, bone grafting combined with autologous bone marrow mononuclear cells transplantation for the treatment of early avascular necrosis of the femoral head.  
    METHODS: From March 2011 to June 2012, 25 patients (33 hips) were treated, including 15 males and 10 females, aged 18-55 years old (34.6 on average). The average disease course was 14 months (range, 8-20 months). Based on the etiology, there were 5 steroid-induced cases (7 hips), 4 alcohol-induced cases (5 hips), 16 idiopathic cases (21 hips). According to the system of the Association Research Circulation Osseous (ARCO), 8 hips were classified as stage IIA, 15 hips as stage IIB, 9 as stage IIC, 1 as stage IIIA. Before treatment, the Harris score was (55.2±6.5) points, visual analog scale score was (6.81±1.19) points, and the volume of the necrotic femoral head with MRI was (13.38±5.1) cm3. After treatment with debridement, bone grafting combined with autologous bone marrow mesenchymal stem cells transplantation, the Harris score, visual analog scale score and the volume of the necrotic femoral head with MRI were measured.
    RESULTS AND CONCLUSION: All incisions healed by first intention. All the 25 patients (33 hips) were followed up for 12-18 months (15 on average). The Harris score was significantly higher, but the visual analog scale score and the volume of the necrotic femoral head were significantly lower at 3, 6, 12 months after operation compared 
    with baseline data (P < 0.05). At postoperative 1 year, the Harris score was (85.6±7.8) points, the visual analog score was (2.38±0.73) points, and the volume of the femoral head necrosis was (7.23±3.3) cm3. There were 15 hips of excellent, 11 of good, 4 of fair and 3 of poor. Three poor hips were subjected to total hip arthroplasty at last. These findings indicate that the debridement, bone grafting combined with transplantation of autologous bone marrow mononuclear cells is an effective method to treat early early osteonecrosis of the femoral head, but the long-term effect needs to be observed further.


    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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    Intra-articular injection of sodium hyaluronate versus placenta-derived mesenchymal stem cells-differentiated chondrocytes for treatment of knee osteoarthritis
    Li Zhi, Zhao Wei, Liu Wei, Zhou Ye, Jia Jing-qiao, Yang Li-feng
    2014, 18 (50):  8140-8146.  doi: 10.3969/j.issn.2095-4344.2014.50.018
    Abstract ( 288 )   PDF (942KB) ( 809 )   Save

    BACKGROUND: Placenta-derived mesenchymal stem cells have been shown to have a strong proliferative capacity, which can be induced to differentiate into nerve cells, vascular endothelial cells, epithelial cells and islet-like cells, but there are few studies about the chondrogenic differentiation in the treatment of knee osteoarthritis.
    OBJECTIVE: To compare the intra-articular injection of sodium hyaluronate and placenta-derived mesenchymal stem cells-induced chondrocytes for treatment of knee osteoarthritis.
    METHODS: (1) Knee osteoarthritis models were established in the left hind of New Zealand white rabbits. After 
    5.5 weeks of plaster fixation, the articular cartilage was observed under microscope. (2) Human placenta-derived mesenchymal stem cells were isolated and cultured using IV collagenase digestion, and flow cytometry was used to detect cell surface markers to identify the placenta-derived mesenchymal stem cells. Passage 3 placenta-derived mesenchymal stem cells were cultured in chondrocyte induction medium and observed under inverted microscope. (3) The rabbits were randomly divided into sodium hyaluronate group, placenta-derived mesenchymal stem cells group, and induced chondrocyte group, and then intra-articular injection of sodium hyaluronate, placenta-derived mesenchymal stem cells, and induced chondrocyte was given, respectively. After 1-5 weeks, the knee cartilage was taken and observed under microscope.
    RESULTS AND CONCLUSION: In vitro cultured human placenta-derived mesenchymal stem cells proliferated to produce a large amount of adherent cells with typical mesenchymal cell morphology; after culture in inducing culture medium, cells presented with micelles and could not proliferate to form adherent cells. There were no adherent cells on the micelles base, showing human placenta-derived mesenchymal stem cells can differentiate into chondrocytes. Under hematoxylin-eosin staining, rabbit articular cartilage was repaired in all the groups, but the intra-articular injection of chondrocytes differentiated from placenta-derived mesenchymal stem cells were better than the intra-articular injection of sodium hyaluronate and placenta-derived mesenchymal stem cells.


    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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    Hematopoietic stem cell transplantation in combination with imatinib mesylate for treatment of Philadelphia-positive leukemia
    Li Meng-xing, Wang Ji-shi, Zhang Yan, Sun Zhi-qiang, Zhao Peng, Lu Ying-hao
    2014, 18 (50):  8147-8150.  doi: 10.3969/j.issn.2095-4344.2014.50.019
    Abstract ( 260 )   PDF (471KB) ( 456 )   Save

    BACKGROUND: Hematopoietic stem cell transplantation is recognized as the only method of curing Philadelphia-positive leukemia. Imatinib mesylate is a competitive inhibitor of the BCR/ABL tyrosine kinase, which has been used more and more in the treatment of Philadelphia-positive leukemia.
    OBJECTIVE: To observe the curative effect of imatinib mesylate combined with allogeneic hematopoietic stem cell transplantation for treatment of Philadelphia-positive leukemia.
    METHODS: We retrospectively analyzed the clinical effect of 12 patients with Philadelphia-positive leukemia who were treated with the combined therapy of imatinib mesylate and allogeneic hematopoietic stem cell transplantation from January 2011 to October 2012, and reviewed the relevant literatures.
    RESULTS AND CONCLUSION: Hematopoietic reconstitution was achieved in all 12 patients and the median times of neutrophil recovery and platelet recovery were 15 and 18 days, respectively. Of the 12 patients, 7 patients developed acute graft-versus-host disease II, 1 developed acute graft-versus-host disease III, 7 developed localized chronic graft-versus-host disease, and 3 developed extensive chronic graft-versus-host disease. Leukemia-free survival rate was 66.7%, and transplant-related mortality was 25.0%. The overall survival rate of HLA-matched sibling donors was 75.0%. The mean disease-free survival period was 8.5 months (7-17 months), and the time needed for BCR/ABL becoming negative was 2-5 months. As an effective and safe method for Philadelphia-positive leukemia, allogeneic hematopoietic stem cell transplantation combined with imatinib mesylate before and after transplantation reduces the leukemia cell load before transplantation, inhibits the proliferation of residual leukemia cells, and promotes full chimerism change.


    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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    pEGFP-N1 transfection of rat dental follicle cells under ultrasound-mediated lipid microbubble: transfected cells have a relatively stable biological property
    Ran Ling, Li Xiao-qian, Jiang Xin-yi, Deng Feng, Song Jin-lin, Cao Li
    2014, 18 (50):  8151-8155.  doi: 10.3969/j.issn.2095-4344.2014.50.020
    Abstract ( 313 )   PDF (924KB) ( 461 )   Save

    BACKGROUND: With the interaction of ultrasound and microbubbles, cavitation and mechanical effects undermine the integrity of the cell membrane, resulting in temporary and reversible holes, increasing the permeability of cell membranes, enhancing gene transfer and improving gene transfection efficiency.
    OBJECTIVE: To investigate the efficiency and safety of rat dental follicle cells transfected with pEGFP-N1 plasmid mediated by microbubble under ultrasonic irradiation.
    METHODS: The primary dental follicle cells from newborn rats were cultured in vitro and passaged to the 4th generation. Under different conditions, pEGFP-N1 was used to transfect rat dental follicle cells. By combining the ultrasonic intensity (0.5, 1 W/cm2) with the irradiation time (15, 30, 45, 60 seconds), we got the best conditions of ultrasonic irradiation for the next experiment. There were five groups: plasmid, microbubble+plasmid, ultrasound+plasmid, ultrasound+microbubble+plasmid, and liposomes+plasmid groups. The expression of pEGFP was observed by inverted fluorescence microscope 48 hours after transfection, and meanwhile, the proliferation inhibition rate of rat dental follicle cells was determined by MTT method. 
    RESULTS AND CONCLUSION: Under the 0.5 W/cm2 ultrasound for 30 seconds, the transfection efficiency was obviously higher than that under the other combinations. Under the above-mentioned condition, the transfection efficiency of rat dental follicle cells with pEGFP-N1 plasmid was higher than that mediated by the traditional liposome, and the cell viability had no obvious changes. Under suitable conditions, ultrasound microbubble technology can safely and effecitively mediate the transfection of rat dental follicle cells with pEGFP-N1 plasmid, and transfected cells also have a stable biological property as normal dental follicle cells. Therefore, ultrasound microbubble technology can provide an ideal method of gene transfection in periodontal tissue engineering.


    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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    MicroRNA-21 can promote the differentiation of neural crest stem cells from human follicle into Schwann cells
    Wang Yan-hua, Liu Hao, Xin Hong, Bai Xiao-xue, Liu Xue-juan, Ni Yu-xin
    2014, 18 (50):  8156-8161.  doi: 10.3969/j.issn.2095-4344.2014.50.021
    Abstract ( 253 )   PDF (827KB) ( 603 )   Save

    BACKGROUND: MicroRNAs are a class of non-coding single-stranded small RNA molecules containing 18–25 nucleotides that can bind to the 3’UTR of the mRNA molecules and regulate the protein expression of target genes. Studies have shown that microRNAs could regulate Schwann cell differentiation, myelination maturation and growth of the peripheral nerve.
    OBJECTIVE: To observe the expression of miR-21 during the differentiation of neural crest stem cells from human follicle into Schwann cells.
    METHODS: Hair follicle stem cells were cultured and neural crest stem cells were separated from human hair follicles by flow cytometry. Then, the neural crest stem cells were induced to differentiate into Schwann cells. 
    qRT-PCR was used to detect the expression of miR-21 in the process of induction. Neural crest stem cells from hair follicles were divided into control group, agomir-21 group, agomir-NC group, antagomir-21 group and antagomir-NC group. The control group was without intervention. Agomir-21 group was transfected with miR-21 agonist, whereas Antagomir-21 group was transfected with miR-21 antagonist. agomir-NC group and antagomir-NC group were respectively negative controls of agomir-21 group and antagomir-21 group. Finally, the possible target of miR-21 was searched in database.
    RESULTS AND CONCLUSION: Neural crest stem cells were successfully separated from human hair follicles using flow cytometry and induced to differentiate into Schwann cells. In the process of cell differentiation, miR-21 expression was upregulated gradually. Transfection of miR-21 agonist could enhance the stem cell differentiation into Schwann cells, whereas transfection of miR-21 antagonist could weaken the differentiation capacity of stem cells. Furthermore, we found via database searching that SOX2 maybe a target of miR-21 and participate in the regulatory role of miR-21. This study suggested that hair follicle neural crest stem cells can be used as an important source of Schwann cells and miR-21 can promote the differentiation.


    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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    MHC molecule expression in dental pulp stem cells and mixed lymphocyte proliferation in vitro
    Nie Shan-shan, Liu Jia, Zhang Rui-han, Wang Xuan, Li Bo-qi, Sun Da-lei, Refukati, Liu Yi-shan
    2014, 18 (50):  8162-8167.  doi: 10.3969/j.issn.2095-4344.2014.50.022
    Abstract ( 202 )   PDF (1777KB) ( 302 )   Save

    BACKGROUND: If differentiated dental pulp stem cells have immune adjustment ability similar to undifferentiated ones, they could become a new source of allogeneic seed cells in tissue engineering.
    OBJECTIVE: To study the immunological properties of dental pulp stem cells and their immunomodulatory effects on lymphocytes in vitro.
    METHODS: Dental pulp stem cells were isolated from mouse dental pulp tissue. Cells at passage 2 were detected using flow cytometry for the expression of MHC-I, MHC-II. Inguinal lymphcells were cultured with allogeneic dental pulp stem cells at a density of 1×105 cells per well. Dental pulp stem cells at 1×105 cells per well or interferon-γ-treated dental pulp stem cells were added into the mixed lymphocyte reaction system to observe lymphocyte proliferation.
    RESULTS AND CONCLUSION: Flow cytometry showed that undifferentiated dental pulp stem cells expressed MHC-I but not MHC-II. After intervention with interferon-γ for 48 hours, increased expression of MHC-I could not been seen in the dental pulp stem cells, but MHC-II expression was increased obviously. No lymphocyte response was induced by allogeneic or interferon-γ-treated dental pulp stem cells as stimulators. Experimental findings suggest that dental pulp stem cells can modulate the proliferation of lymphocytes, which may be expected to become a new source of allogeneic seed cells in tissue engineering or cell therapy.


    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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    Protein extracts from human embryonic brain tissue induce the neuronal differentiation of mesenchymal stem cells from human placenta
    Ma Li-jun, Fan Heng, Ma Xiao-na, Wei Jun, Li Yu-kui
    2014, 18 (50):  8168-8173.  doi: 10.3969/j.issn.2095-4344.2014.50.023
    Abstract ( 263 )   PDF (1779KB) ( 321 )   Save

    BACKGROUND: It is a key to choose an appropriate method to trans-differentiate mesenchymal stem cells from human placenta into neuron-like cells for clinical treatment of neural system injury.
    OBJECTIVE: To observe the feasibility of the neuronal differentiation of mesenchymal stem cells from human placenta with protein extracts of human embryonic brain tissue.
    METHODS: Mesenchymal stem cells from human placenta were isolated and cultured using enzyme digestion method. The third passage of cells were incubated in induction medium containing protein extracts of human embryonic brain tissue for 6 days, and then cultured in culture medium containing 20 nmol/L all-trans retinoic acid and 500 μg/L sonic hedgehog for 3 days, followed by 3-day continuous culture in 10 μg/L brain-derived neurotrophic factor, 20 μg/L glial cell line-derived neurotrophic factor, 50 μg/L insulin-like growth factor type II
    RESULTS AND CONCLUSION: The adherent cells were obtained after enzyme digestion of placenta tissue. The passage 2 cells were fusiform-shaped and exhibited a whirlpool-like growth. The passage 3 cells were uniform in 
    morphology. After induction, immunocytochemistry assay showed that the cells expressed neuron-specific enolase, nestin, glial fibrillary acidic protein, neurofilament protein, and nerve growth associated protein 43; ELISA results showed that cells were positive for brain-derived neurotrophic factor, neurotrophin 3, neurotrophin 4; RT-PCR results showed that cells were positive for microtubule-associated protein, neuron-specific enolase, neurofilament protein, nerve growth associated protein 43. Results indicate that mesenchymal stem cells from human placenta can differentiate into neuron-like cells under induction of protein extracts of human embryonic brain 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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    Autologous peripheral blood stem cell transplantation combined with core decompression for the treatment of avacscular necrosis of the femoral head in patients with systemic lupus erythematosus
    Yu Lian, Chen Long-tian, Lai Qin, Qiu Yong-long, Huang Jian-qing, Lin Qi, Wu Fu-chun
    2014, 18 (50):  8174-8179.  doi: 10.3969/j.issn.2095-4344.2014.50.024
    Abstract ( 285 )   PDF (2676KB) ( 401 )   Save

    BACKGROUND: There are less studies addressing whether the clinical outcomes about the autologous peripheral blood stem cell transplantation combined with core decompression for the treatment of systemic lupus erythematosus with avascular necrosis of the femoral head are different from the simple core decompression.
    OBJECTIVE: To observe the clinical outcomes of autologous peripheral blood stem cell transplantation combined with core decompression for the treatment of systemic lupus erythematosus with avascular necrosis of the femoral head.
    METHODS: Systemic lupus erythematosus patients with avascular necrosis of the femoral head admitted at the Affiliated Longyan First Hospital of Fujian Medical University from October 2004 to October 2014 were enrolled and divided into transplantation group (n=22) and control group (n=26) according to different therapies. Patients in the two groups were subjected to autologous peripheral blood stem cell transplantation combined with core decompression and simple core decompression, respectively.
    RESULTS AND CONCLUSION: In the transplantation group, the levels of white blood cells, C-reactive protein, C3 and C4 as well as erythrocyte sedimentation rate were significantly increased at 1 week after treatment, while the levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, serum creatinine, uric acid, IgM, IgG, IgA, ds-DNA levels still maintained in the normal range. Compared with the control group, the Harris scores were increased (6, 12, 24 months after treatment) and visual analog scale scores were reduced (12, 24 months after treatment) in the transplantation group after treatment. Moreover, the necrosis area of the femoral head shown on the T1W1 of MRI in the transplantation was also smaller than that in the control group. These findings indicate that the autologous peripheral blood stem cell transplantation combined with core decompression for the treatment of systemic lupus erythematosus with avascular necrosis of the femoral head can remarkably relieve the pain, promote the blood supply in the necrosis area, ameliorate the hip joint function, and prevent the collapse of the femoral head, which is an easy and safe treatment preserving the femoral head in systemic lupus erythematosus patients with avascular necrosis of the femoral head in early and middle stages.


    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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    Chinese medicines induce bone marrow mesenchymal stem cells differentiating into osteoblasts
    Deng Hui, Luo Jun
    2014, 18 (50):  8180-8183.  doi: 10.3969/j.issn.2095-4344.2014.50.025
    Abstract ( 323 )   PDF (548KB) ( 488 )   Save

    BACKGROUND: Recent studies have shown that Chinese medicines appear to have an active inducible role in the osteogenic differentiation of bone marrow mesenchymal stem cells.
    OBJECTIVE: To review the progress of Chinese medicine in the induced differentiation of bone marrow mesenchymal stem cells into osteoblasts.
    METHODS: A computer-based search of Wanfang database was performed to retrieve articles addressing Chinese medicine for inducing osteogenic differentiation of bone marrow mesenchymal stem cells, published from January 2004 to April 2012. The key words were “Chinese medicine, bone marrow mesenchymal stem cells, osteoblasts” in Chinese. Finally, 18 articles were included in result analysis.
    RESULTS AND CONCLUSION: Based on serum pharmacology, serum containing Chinese medicine cannot only remove unknown toxicity, but also reflect the efficacy of Chinese medicine. Therefore, serums containing drugs for tonifying the kidney and bone knitting have been used to induce differentiation of bone marrow mesenchymal stem cells into osteoblasts. These serums containing single herbs, single herb extracts, and drug compounds are characterized as safe and easy to use, which can all promote in vitro differentiation of bone marrow mesenchymal stem cells into osteoblasts.


    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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    Stem cell therapy for obstructive nephropathy: current situation and problems
    Lv Chun-yan, Li Juan
    2014, 18 (50):  8184-8188.  doi: 10.3969/j.issn.2095-4344.2014.50.026
    Abstract ( 299 )   PDF (650KB) ( 436 )   Save

    BACKGROUND: Thought of treatment of obstructive renal fibrosis is mainly concentrated at relieving the kidney stone, renal pelvis and ureter stenosis as well as at epithelial mesenchymal transition, renal fibrosis related factors and improving the renal interstitial microcirculation. At present, the therapeutic effect is not ideal. However, regenerative medicine based on stem cells may bring a new hope for the treatment of obstructive renal fibrosis.
    OBJECTIVE: To summarize the mechanism and progress in different sources of stem cells in the treatment of obstructive renal fibrosis.
    METHODS: The database of PubMed, Ovid MEDLINE, CNKI full text database, VIP database, Wanfang database were retrieved to collect articles about stem cell therapy for obstructive renal fibrosis. The key words were “stem cells, obstructive nephropathy, renal fibrosis” in Chinese and English. Finally, there were 51 articles included in result analysis.
    RESULTS AND CONCLUSION: Stem cell therapy for obstructive nephropathy is still in the experimental stage. A large number of studies have shown that stem cell transplantation has positive effects on the treatment of obstructive renal interstitial fibrosis. Stem cells can be located in the renal interstitium after transplantation to differentiate into renal tubular epithelial cells, thereby promoting the recovery of renal fibrosis. Stem cells are able to secrete, up- or down-regulate some cytokines to treat fibrosis. If the obstruction is relieved timely and early, stem cell transplantation may become a novel treatment for obstructive renal 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


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    Stem cell transplantation in the treatment of myocardial infarction: a visual analysis of international research forefront and development trend
    Li Xuan, Shi Chun-lai, Wang Xue-yan, Zhang Ming
    2014, 18 (50):  8189-8195.  doi: 10.3969/j.issn.2095-4344.2014.50.027
    Abstract ( 287 )   PDF (784KB) ( 689 )   Save

    BACKGROUND: Stem cell transplantation as a new therapy for myocardial infarction has been used more in animal studies, but its clinical application is still faced with many problems, such as choosing the transplantation pathway, inducing the differentiation of transplanted cells, and how to control arrhythmia.
    OBJECTIVE: Based on the data from Web of Science database and ClinicalTrials.gov, to analyze the international development trends of stem cell transplantation in the treatment of myocardial infarction, thereby providing a reference basis for relevant researches in this field.
    METHODS: (1) The keywords were “stem cell transplantation” and “myocardial infarction”. (2) Time span: 2004-2013. (3) Data source: Web of Science, Citespace III, and ClinicalTrials.gov.
    RESULTS AND CONCLUSION: (1) Totally 2 912 literatures addressing stem cell transplantation for myocardial infarction included in Web of Science database from 2004 to 2013 are enrolled and analyzed based on Web of Science database literature analysis report and export information function, using Citespace III information visualization software, to draw co-citation network map. Finally, there are eight high-core classic literatures. (2) There are totally 2 912 articles addressing stem cell transplantation for myocardial infarction included in Web of Science database from 2004 to 2013. Among these 2 912 articles, 1 040 articles are from USA, accounting for 35.714%. The institutions publishing more literatures about stem cell transplantation for myocardial infarction from 2004 to 2013 are Stanford University, Harvard University, Chinese Academy of Medical Sciences, Cincinnati 
    University, and University of Toronto. Circulation is the journal that has published the most papers (123 papers, accounting for 4.224%) addressing stem cell transplantation for myocardial infarction. The overall number of literatures about stem cell transplantation for myocardial infarction exhibits a gradually increasing trend. The 494 of 2912 papers come from China, which is secondary to the USA. It indicates that there are more scientific achievements in this field in China. (3) There are 22 relevant items registered in ClinicalTrials.gov from 2004 to 2013, all of which belong to interventional studies.


    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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    C-kit+ cardiac stem cells for ischemic heart disease: research status, challenges and prospects
    Meng Tian-tian, Li Shu-ren
    2014, 18 (50):  8196-8200.  doi: 10.3969/j.issn.2095-4344.2014.50.
    Abstract ( 300 )   PDF (573KB) ( 531 )   Save

    BACKGROUND: C-kit+ cardiac stem cells with high self-renewal ability can specifically differentiate into cardiac structural cells, which are considered for the most promising stem cell type to completely repair myocardial regeneration in patients with ischemic heart disease and other end-stage heart diseases.
    OBJECTIVE: By reviewing the discovery, origin, characteristics, research progress of cardiac stem cells in the treatment of patients with ischemic heart disease as well as the existing problems and possible solutions, to strengthen the understanding about the characteristics of the C-kit+ cardiac stem cells in order to better predict the biological behavior.
    METHODS: A computer-based search of PubMed (2003-01/2014-06) was performed to collect articles about cardiac stem cells. The key words included “stem cell, C-kit+ cardiac stem cells, cardiac infarction”. Articles related to C-kit+ cardiac stem cells published recently or in high-impact journals were initially surveyed and finally 38 articles were included and summarized.
    RESULTS AND CONCLUSION: C-kit+ cardiac stem cells have been confirmed to improve heart function and ventricular remodeling in animals, and recently SCIPIO phase I clinical studies have also confirmed that the C-kit+ cardiac stem cells could improve cardiac function and quality of life in patients with ischemic heart diseases. Although transplanted cells are found quickly lost and cannot repair fibrous scar, its beneficial effects on the heart
    is not stopped with the loss of seed cells, but can persist for a long time, which is considered to be mainly related to paracrine effects of various cytokines. Currently, it has brought new hope for stem cell therapy to end-stage heart diseases, but the survival and differentiation of the stem cells after transplantation still to be further studied.


    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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