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05 November 2010, Volume 14 Issue 45 Previous Issue    Next Issue

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Wnt signaling molecules induce the differentiation of bone marrow mesenchymal stem cells into neuron-like cells Tang Yu, Ma Yun-sheng, Qin Shu-jian　 2010, 14 (45):  8361-8364.  doi: 10.3969/j.issn.1673-8225.2010.45.001 Abstract ( 306 )   PDF (606KB) ( 389 )   Save BACKGROUND: Mesenchymal stem cells (MSCs) could differentiate into nerve cells, but the molecular mechanism is still unknown. OBJECTIVE: To observe effects of Wnt3a and Wnt5a on differentiation of bone marrow mesenchymal stem cells (BMSCs) into nerve cells. METHODS: The rat BMSCs were separated and cultured in vitro. Following passage, expression of CD14, CD44, CD9, CD34 and CD45 was detected by morphology and flow cytometry. Wnt3a, Wnt5a contained with basic fibroblast growth factor (bFGF) were used to induce the differentiation of BMSCs into neuron-like cells. Wnt3a and Wnt5a effects were identified by immunohistochemistry and RT-PCR. RESULTS AND CONCLUSION: BMSCs were fibroblast-like. CD9 and CD44 were highly expressed, but CD34 and CD45 low expressed. Nestin and neuron specific enolase (NSE) were positive and glial fibrillary acidic protein (GFAP) was not positive when they was cultured with Wnt3a. In Wnt5a group, Nestin was weak positive, but NSE and GFAP were negative. The RT-PCR results revealed Nestin expressed before and after induction; NSE was significant at 5 days following induction, especially at 10 days; weak GFAP expression was detectable at 10 days in Wnt3a group. These indicated that Wnt3a can promote the differentiation of BMSCs into neuron-like cells. Related Articles | Metrics

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Optimization of small interfering RNA-mediated RhoA silencing in bone marrow mesenchymal stem cell cultures Lü Gang, Yao Xin 2010, 14 (45):  8365-8368.  doi: 10.3969/j.issn.1673-8225.2010.45.002 Abstract ( 300 )   PDF (353KB) ( 511 )   Save BACKGROUND: Previous culture method of bone marrow mesenchymal stem cells (BMSCs) has problems such as senescence and low differentiation rate. OBJECTIVE: To determine whether the RhoA gene silencing can optimize BMSC cultures. METHODS: BMSCs from Sprague Dawley rats were cultured in vitro, and were transfected by small interfering RNA (siRNA) to knock down the expression of RhoA. BMSCs were divided into three groups: stem cell group (non-transfection of siRNA), disrupted by random sequence siRNA transfection stem cell group, and siRNA transfection of stem cell group. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blot assay were used to assess RhoA gene and protein expression before and after transfection. Cellular proliferation optimization was determined by the cell growth curve and MTT assay. The cell cycle was analyzed by flow cytometry. RESULTS AND CONCLUSION: Expression of RhoA gene and protein was significantly reduced following transfection of siRNA compared with stem cell group (P < 0.05). The cell growth speed was significantly increased, the cell cycle of G0/G1 phase was decreased and cell number in S phase was increased (P < 0.05). These indicated that the RhoA gene silencing can promote BMSC proliferation, and optimize culture methods.  Related Articles | Metrics

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Expression of alpha-fetoprotein and albumin in bone marrow mesenchymal stem cells induced by hepatic failure rat serum Wang Ying, Zhao Wen-jing, Ye Dong-xia, Liu Shu-rong 2010, 14 (45):  8369-8372.  doi: 10.3969/j.issn.1673-8225.2010.45.003 Abstract ( 299 )   PDF (412KB) ( 416 )   Save BACKGROUND: It was found that hepatocyte growth factor, fibroblast growth factor-4 and epidermal growth factor could induce differentiation of bone marrow mesenchymal stem cells (BMSCs) into hepatocytes. There were no reports on the inducing effect of hepatic failure rat serum on BMSCs. OBJECTIVE: To study the effects of hepatic failure rat serum on the induced differentiation of BMSCs. METHODS: BMSCs were isolated from SD rat femur and tibia by density gradient centrifugation and culture in vitro. BMSCs were cultured in DMEM containing the hepatic failure rat serum and conventional culture medium as control. The morphological changes of cells were observed and the expression of alpha-fetoprotein and albumin was measured by immunocytochemistry method on 14 days. RESULTS AND CONCLUSION: Obvious morphological changes were observed on 14 day, which showed that BMSCs became slightly large and flat cells as epithelial cells. The positive rates of alpha-fetoprotein and albumin were (54.8±7.64)% and (45.9±9.68)% respectively. Cells in the control group did not have morphological changes, no alpha-fetoprotein and albumin expression. The results showed that BMSCs can be induced to express alpha-fetoprotein and albumin by hepatic failure rat serum. Related Articles | Metrics

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Proliferation and collagen production of bone marrow mesenchymal stem cells cultured in platelet-rich plasma in vitro  Cao Wen, Yao Guang-hui, Chen Yu-hua, Ji Li-na, Huang Hui, Xia Chang-suo 2010, 14 (45):  8373-8376.  doi: 10.3969/j.issn.1673-8225.2010.45.004 Abstract ( 269 )   PDF (360KB) ( 408 )   Save BACKGROUND: Mesenchymal stem cells (MSCs) are seed cells that can be obtained greatly for tendon tissue engineering, but how to induce to differentiate into functional tendon-like cells in vitro is a key technology. OBJECTIVE: To explore the effect of platelet-rich plasma (PRP) on proliferation and collagen production of MSCs cultured in vitro. METHODS: Rabbit bone marrow mesenchymal stem cells (BMSCs) were isolated and cultured. Autologous PRP was used to intervene BMSCs. We set up PRP-high dose, PRP-moderate dose and PRP-low dose groups and a blank control group. Cells were counted and cell growth curve was drawn. Methyl thiazolyl tetrazolium assay was utilized to analyze BMSCs survival and proliferation ability in each group. Enzyme linked immunosorbent assay was employed to detect collagen. Reverse transcription-polymerase chain reaction was used to determine expression of type Ⅰ collagen gene prior to and following PRP intervention. RESULTS AND CONCLUSION: BMSCs had high proliferative activity, showing rapid growth and great curve upgrade range in the PRP-high dose, PRP-moderate dose and PRP-low dose groups, which showed significant difference as compared with blank control group (P < 0.05). Long culture time exhibited significant effect. Following culture for a while, its effect presented dose dependence. High dose of PRP had significant proliferative effect. PRP could obviously promote type Ⅰ and Ⅲ collagen synthesis in BMSCs. High dose showed significant effects on stimulating collagen production. These suggest that BMSCs had basic conditions of tissue engineered tendon seed cells. PRP can induce MSC to transform into tendon cells. Related Articles | Metrics

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Biological characteristics and regulatory effects of bone marrow mesenchymal stem cells on hematopoietic stem cells in patients with chronic myelocytic leukemia Zhu Xi-shan, Song Yu-guang, Zhang Hong-mei, An Guang-yu 2010, 14 (45):  8377-8381.  doi: 10.3969/j.issn.1673-8225.2010.45.005 Abstract ( 298 )   PDF (809KB) ( 388 )   Save BACKGROUND: Chronic myelocytic leukemia had abnormal hematopoietic microenvironment and abnormal immunology. We presumed that mesenchymal stem cells (MSCs) may play an important role in pathological process of chronic myelocytic leukemia. OBJECTIVE: To investigate biological characteristics of chronic myeloid leukemia hemangioblasts and its regulatory effects, and to compare the differences with bone marrow mesenchymal stem cells (BMSCs) from normal donors. METHODS: MSCs were isolated from normal donors and BMSCs from patients with chronic myelocytic leukemia. The differences in morphology, phenotype, cell growth and T lymphocyte activation were examined. Obtained cells were cocultured with umbilical cord blood stem cells. The effects on colony formation and differences in relative molecule expression were determined in coculture system. RESULTS AND CONCLUSION: There were no differences in morphology, phenotype and doubling time of MSCs from patients and normal donors. Inhibitory ability of BMSCs on T cell activation was weakened in chronic myelocytic leukemia patients. In coculture system, suspended cells became more, which indicated that the adherence between hematopoietic stem cells and MSCs was weakened. Simultaneously, protein and RNA levels revealed that matrix metalloproteinase-9 levels increased, and KitL of intercellular adhesion molecule-1 changed from membrane form into soluble form. The results showed that BMSCs of chronic myelocytic leukemia patients were the microenvironment of cell differentiation and development. Its basic mechanisms were the degradation of matrix metalloproteinase-9 on extracellular matrix and split of adhesion molecule. Changes in bone marrow microenvironment support effects on adhesion, proliferation and differentiation of hematopoietic stem cells lead to abnormal proliferation and mobilization of hematopoietic stem cells, decrease sensitivity of cancer cells on immunocytes, resulting in immune escape. Related Articles | Metrics

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In vitro cultivation and multi-inducing differentiation of rabbit bone marrow mesenchymal stem cells Zhang Rong, Shen Kai-jin, Liu Yan-pu 2010, 14 (45):  8382-8385.  doi: 10.3969/j.issn.1673-8225.2010.45.006 Abstract ( 257 )   PDF (377KB) ( 483 )   Save BACKGROUND: There is still no unified standard and final conclusion of isolation, culture and evaluation of bone marrow mesenchymal stem cells (BMSCs). OBJECTIVE: To observe the biological characteristics and multi-differentiation potential of BMSCs through in vitro cultivation, purification, and amplification. METHODS: BMSCs were isolated and cultured by adherence screening method, followed by observation of proliferation and growth characteristics, for drawing growth curves; inverted phase contrast microscope, hemotoxylun and eosin staining, and alkaline phosphatase staining were used to observe the cell morphology; BMSCs were induced to differentiate into osteoblasts, chondrocytes and vascular endothelial cells, which were identified by calcified nodules-Alizarin red, toluidine blue and Ules europaeus agglutinin (UEA) staining respectively. RESULTS AND CONCLUSION: By the method of adherence screening, BMSCs were found in stable characteristic, appeared morphologically in spindle and colony-shape, expressed weakly positive of Alkaline phosphatase staining. BMSCs presented with the corresponding cytomorphology and cytobiology characteristics after inducing cultivation of osteoblasts, chondrocytes and vascular endothelial cells. It revealed that adherence screening method is relatively simple and feasible. Furthermore, BMSCs have a good ability of proliferation and could multi-differenrate under suitable condition. Related Articles | Metrics

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Biological characteristics of human placenta-derived mesenchymal stem cells versus human bone marrow-derived mesenchymal stem cells Zhang Hong-yan, Yang Nai-long, Sun Xiao-juan, Xu Li-li 2010, 14 (45):  8386-8389.  doi: 10.3969/j.issn.1673-8225.2010.45.007 Abstract ( 274 )   PDF (420KB) ( 381 )   Save BACKGROUND: Human bone marrow-derived mesenchymal stem cells (BMSCs) have a great clinical value, but limited by the number and source, in contrast, human placenta-derived mesenchymal stem cells (PMSCs) have become an important cellular source in regenerative medicine and the stem cells of the most promising clinical application. OBJECTIVE: To compare the differences in isolation and culture in vitro, amplification and differences in biological characteristics between PMSCs and BMSCs. METHODS: Human placentas were isolated by collagenase and bone marrows were isolated by density gradient centrifugation. 10% fetal calf serum was added to the LG-DMEM culture medium and cells were digested and passaged after converging to 90%. The third generation of PMSCs and BMSCs were vaccinated in the concentration of 1 × 106 and replaced by fat cells differentiated culture medium after converging to 70%-80% and induced for 16 days. RESULTS AND CONCLUSION: PMSCs and BMSCs had the adherent growth ability, morphology of fibroblast-like cells and spindle-shaped appearance, but the latter had the slightly smaller size. Both BMSCs and PMSCs highly expressed CD29, CD44, did not express CD34, CD106. Both could be differentiated into adipose cells. Cell morphology and growth characteristics are basically the same between BMSCs and PMSCs, both can amplify in vitro, differentiate into adipose cells and can be used as another source of adult stem cells in tissue engineering, but PMSCs have the better application prospects. Related Articles | Metrics

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Expression of estrogen and progestagen receptors in human placental mesenchymal stem cells Sha Wen-qiong, Wang Zi-neng,Su Fang-ming 2010, 14 (45):  8390-8393.  doi: 10.3969/j.issn.1673-8225.2010.45.008 Abstract ( 437 )   PDF (624KB) ( 421 )   Save BACKGROUND: It has been shown that estrogen and progestogen regulate bone marrow mesenchymal stem cells by the estrogen and progestagen receptors expressed in them. The high concentrations of estrogen and progestogen in placenta may also have effects on human placental mesenchymal stem cells (MSCs). OBJECTIVE: To investigate the estrogen and progestagen receptors expression of human placental MSCs. METHODS: Human placental MSCs were isolated and cultured in vitro. The cell surface markers were determined by flow cytometry. These cells were also induced to osteogenic and adipogenic differentiation. The expression of estrogen and progestagen receptors was detected by fluorescent quantitative polymerase chain reaction and immunohistochemical method. RESULTS AND CONCLUSION: Human placental MSCs were positive for CD29, CD44, CD73, CD90, CD105 and HLA-ABC, but negative for CD34, CD45, CD14 and HLA-DR. Placental MSCs could be induced to osteoblasts and adipocytes. PCR results showed that the amplification efficiency of estrogen receptor β-mRNA was even lower than it (△Ct: 25.2±0.71), while amplification efficiency of estrogen receptor α-mRNA was low (△Ct: 20.64±2.27). The progestagen receptor had better amplification efficiency  (△Ct: 16.11±1.9). The immunohistochemical results exhibited that positive rate of progestagen receptor was (18.81±9.16)%, but no estrogen receptor was detected in all samples. These data indicate that parts of human placental MSCs expressed progestagen receptor, and human placental MSCs expressed low level estrogen receptor α and no estrogen receptor β. Related Articles | Metrics

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Toxicity of lipopolysaccharide-induced activated microglia to oligodendrocyte precursor cells He Ya-fang, Chen Hui-jin, Qian Long-hua, Chen Guan-yi 2010, 14 (45):  8394-8398.  doi: 10.3969/j.issn.1673-8225.2010.45.009 Abstract ( 298 )   PDF (383KB) ( 652 )   Save BACKGROUND: Studies have confirmed that localized activation of microglia, however, has been implicated in the pathogenesis of a number of neurological diseases and disorders, such as multiple sclerosis and periventricular leukomalacia (PVL). OBJECTIVE: To explore the toxicity of lipopolysaccharide (LPS)-induced activated-microglia to oligodendrocyte precursor cells. METHODS: Co-cultured microglias and oligodendrocyte precursor cells obtained from two-day-old Sprague-Dawley rats were divided into the co-cultured control group and the co-cultured LPS group. After co-cultured cells were induced by LPS (100 μg/L) for 48 hours, the concentration of nitric oxide was measured by nitric acid-deoxidize colorimetry; the generated levels of (O2-) were determined by deoxidize colorimetry; the levels of peroxynitrite (ONOO-) were detected by immunocytochemistry. The morphologic changes of death oligodendrocyte precursor cells were observed using Hoechst 33342/propidium iodide staining and the survival rate of oligodendrocyte precursor cells was detected by flow cytometry. RESULTS AND CONCLUSION: Compared with co-cultured control group, the levels of nitric oxide, O2-and ONOO- increased significantly in co-cultured LPS group, and with a higher apoptotic rate of oligodendrocyte precursor cells. It is validated in vitro that the death pathway of LPS-induced activated-microglia to oligodendrocyte precursor cells involves in LPS-induced microglia activation, impels microglia to express inducible nitric oxide synthase and to activate NADPH oxidase, results in the overproduction of nitric oxide and O2- , which further forms ONOO-, a primary toxic factor to oligodendrocyte precursor cells, finally leads to oligodendrocyte precursor cells death. Related Articles | Metrics

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Effects of zinc on DNA and protein contents as well as reproductive cycle of human umbilical cord blood-derived mesenchymal stem cells Yao Su-yan, Yang Yi-yong, Qin Shu-jian, Zheng De-yu 2010, 14 (45):  8399-8402.  doi: 10.3969/j.issn.1673-8225.2010.45.010 Abstract ( 425 )   PDF (312KB) ( 343 )   Save BACKGROUND: Zinc has effects on DNA polymerase and RNA polymerase by direct and indirect action, and plays important roles in DNA duplication, RNA transcription, proliferation and differentiation of cells. Some studies have verified that zinc at a suitable concentration has effects on promoting the proliferation of neurons and osteoblasts. OBJECTIVE: To explore effects of zinc on DNA and protein content as well as reproductive cycle of human umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) using flow cytometry, and to investigate zinc at a suitable concentration effects on UCB-MSCs. METHODS: UCB-MSCs were isolated and cultured in vitro by the density gradient centrifugation. At the third passage, BMSCs in the control group were incubated with DMEM/F12 containing fetal bovine serum. BMSCs in the zinc group were incubated in above-mentioned DMEM, supplemented with zinc sulfate. The final concentration of zinc was 0.5, 1.5, 2.5, 3.5, 4.5 and 5.5 mg/L. BMSCs were incubated for 21 days. Cell surface antigen expression was observed. MTT assay was used to detect cell activity. Flow cytometry was utilized to measure DNA content, protein content and reproductive cycle. RESULTS AND CONCLUSION: Cells were positive for CD29 and CD44. Zinc had dose-effect relationship on promotion of BMSC activity. Cell activity was significantly higher in the 0.5-4.5 mg/L zinc group compared with the control group (P < 0.01), especially at 2.5 mg/L. At 7, 14 and 21 days, BMSC DNA content and protein content significantly increased in the 2.5 mg/L zinc group compared with the control group (P < 0.01). Cell percentage in the S and G2+M phases and cell proliferation index significantly increased, but cell percentage in the G0/G1 phases decreased significantly (P < 0.01). These indicate that zinc (0.5-4.5 mg/L) has the effect of promoting the rat BMSC proliferation, DNA reproduction and protein synthesis, and the 2.5 mg/L is the optimal concentration. Related Articles | Metrics

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Ischemic tolerance in the brain and proliferation of autologous neural stem cells in rats Jiang Xiao-feng, Luo Zu-ming 2010, 14 (45):  8403-8406.  doi: 10.3969/j.issn.1673-8225.2010.45.011 Abstract ( 245 )   PDF (281KB) ( 320 )   Save BACKGROUND: Brain ischemic tolerance and autologous neural stem cells have protective effects on the brain, but whether the former can contribute to the proliferation of autologous neural stem cells remains unclear. OBJECTIVE: To explore the relationship between ischemic preconditioning in brain and proliferation of endogenous neural stem cells in the hippocampus at 7 days following cerebral infarction, and to observe influence of ischemic preconditioning on the status of rats’ neurological deficit after cerebral infarction. METHODS: The focal-focal ischemic tolerance models of Sprague Dawley rats were established using the twice suture method. A total of 40 male Sprague Dawley rats were randomly divided into sham surgery group, ischemia group, sham surgery + ischemia group and ischemic preconditioning + ischemia group, with 10 rats in each group. The neurological status was assessed using Zea-Longa neurological deficit scores at 3 and 7 days following cerebral infarction. Fluorescent immunohistochemistry was utilized to determine the number of BrdU-positive cells in the hippocampus of the ischemic side of rats. RESULTS AND CONCLUSION: Zea-Longa neurological deficit scores were lower in the ischemic preconditioning + ischemia group compared with ischemia group and sham surgery + ischemia group at 3 and 7 days following cerebral infarction (P < 0.01). There was no significant difference between ischemia group and sham surgery + ischemia group (P > 0.05). At 7 days following cerebral infarction, the number of BrdU-positive cells in the hippocampus of ischemic side was greater in the ischemia group, sham surgery + ischemia group and ischemic preconditioning + ischemia group compared with sham surgery group (P < 0.01); the number was greater in the ischemic preconditioning + ischemia group compared with ischemia group and sham surgery+ ischemia group (P < 0.01). No significant difference was determined between ischemia group and sham surgery + ischemia group (P > 0.05). Results suggest that ischemic preconditioning could facilitate the proliferation of endogenous neural stem cells in hippocampus dentate gyrus infragranular layer after ischemic cerebral infarction in rats, and improve the status of rats’ neurological deficits. Related Articles | Metrics

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Bromodeoxyuridine labeling of muscle-derived stem cells in vitro: Optimal concentration and time Zhang Xue-pu, Lü Gang, Mei Xi-fan, Zhang Xiao-jian 2010, 14 (45):  8407-8410.  doi: 10.3969/j.issn.1673-8225.2010.45.012 Abstract ( 318 )   PDF (319KB) ( 425 )   Save BACKGROUND: The muscle-derived stem cells transplanted into the body of the animals can repair the defects of bone, muscle, cartilage and neural system. An efficient and safe labeling method is needed to understand the migration, proliferation and differentiation of the cells. OBJECTIVE: To observe the effect of 5-bromodeoxyuridine (Brdu) labeling of muscle-derived stem cells in vitro, to study the optimal dosage and timing. METHODS: Muscle-derived stem cells from Sprague Dawley rats were isolated in vitro using differential adhesion method. The second passage of cells was counted and identified by immunocytochemical staining. The cells were labeled by BrdU at 5, 10, 15, 20 μmol/L to identify the optimal BrdU concentration. Immunocytochemistry was performed to calculate the labeling index. By MTT testing and trypan blue testing, we surveyed the influence of BrdU on the growth of muscle-derived stem cells.  RESULTS AND CONCLUSION: Immunocytochemical staining results showed positive expression of Desmin in MDSCs with the percentage of (85.7±6.0)%. The viability and proliferation between the group labeled by BrdU and the control group were similar (P > 0.05). The rate of the living cells labeled by BrdU was (92.3±2.1)%. The labeling rate was better in the 10, 15, 20 μmol/L groups compared with 5 μmol/L group. The optimal dosage was 10 μmol/L, and the optimal time was 3 days, and the labeling index was (70.9±4.5)% with no significant change over time. It was proved that after labeled by BrdU, no difference in the viability and proliferation was found in muscle-derived stem cells, and the labeling index can come up to the required standards of the transplantation. Related Articles | Metrics

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Effect of short-term low-frequency electrical stimulation on myelin formation of Schwann cells in vitro Wan Li-dan, Ding Wen-long, Li Feng, Xia Rong, Zhu Hao, Liu De-ming, Lin Xue-qun 2010, 14 (45):  8411-8415.  doi: 10.3969/j.issn.1673-8225.2010.45.013 Abstract ( 257 )   PDF (697KB) ( 353 )   Save BACKGROUND: Short-time low-frequency electrical stimulation has the potential to promote axonal regeneration and target selection after peripheral nerve injury. However, studies concerning the effect of electrical stimulation on myelination are still elusive, and the possible target cell (neuron or Schwann cells) on which electrical stimulation impacts remains unknown. OBJECTIVE: To establish the co-culture model of dorsal root ganglion neurons and Schwann cells, and investigate the short-time low-frequency electrical stimulation effect on Schwann cell myelination in vitro. METHODS: Purified dorsal root ganglion neurons were subjected to continuous electrical stimulation (20 Hz, 100 μs, 3 V) for one hour. 24 hours later, the purified Schwann cells suspension was added into pre-stimulated neurons/Schwann cell cultures. At 7 and 14 days after L-ascorbic acid induction, myelin formation was observed and determined. RESULTS AND CONCLUSION: Electrical stimulation enhanced brain-derived neurotrophic factor secretion from purified dorsal root neurons (P < 0.05). Dorsal root neurons treated with electrical stimulation cocultured with Schwann cells, which presented increased myelination and upregulated myelin protein expression (P < 0.05). These results have indicated that short-term low-frequency electrical stimulation promoted Schwann cell myelination in vitro, and the effect was at least initially mediated via the enhancement of neuronal brain-derived neurotrophic factor signals. Related Articles | Metrics

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Treatment of cerebral infarction in rats by transplanting bone marrow mesenchymal stem cells with RhoA gene silencing via the vein Zhou Guo-qing, Jin Yi, Zhang Peng 2010, 14 (45):  8416-8420.  doi: 10.3969/j.issn.1673-8225.2010.45.014 Abstract ( 264 )   PDF (672KB) ( 482 )   Save BACKGROUND: Previous studies have confirmed that RhoA gene plays an important role in nerve damages. To decrease its expression by gene silencing can effectively block secondary nerve damages. RhoA protein mediated neurite growth inhibitory effect is an important reason for affecting repair effect following bone marrow mesenchymal stem cells (BMSCs) transplantation. OBJECTIVE: To determine whether the RhoA gene silencing in BMSCs can enhance curative effects of transplantation by vein of BMSCs on cerebral infarction in rats. METHODS: BMSCs were cultured by the suspension culture in vitro, and were transfected by siRNA to knock down the expression of RhoA gene. Western blot assay was used to assess the knockdown efficiency. The models of cerebral infarction were made by middle cerebral artery occlusion and randomly divided into three groups. RhoA gene silencing of BMSCs suspension, BMSCs suspension and medium without stem cells (control group) were respectively injected via caudal vein. The neurological defect scores were determined at 24 hours, 3 days and 1, 2 weeks after injection. The rats were sacrificed at 2 weeks following model induction. Histological changes in infarct regions were observed using immunohistochemistry and hematoxylin-eosin staining. RESULTS AND CONCLUSION: The expression of RhoA was markedly knocked down by transfection of siRNA at 24 hours after the transfection (P=0.002). Therapeutic effects of BMSCs transplantation following RhoA gene silencing were significantly increased in histology and function. These suggest that RhoA gene in BMSCs can be silenced by RNA interference. BMSCs of RhoA gene silencing transplanted by caudal vein into the cerebral infarction tissues can survive, proliferation, differentiate and migrate in damage sites, and significantly improve the neurological function in rats with cerebral infarction. Related Articles | Metrics

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Effects of bone marrow mesenchymal stem cells modified with brain-derived neurotrophic factor gene on tau protein, beta-amyloid and neuronal ultrastructure in the cerebral cortex and hippocampus of an Alzheimer’s disease rat  Wei Chang-xiu, Dai Hong, Chen Song-lin 2010, 14 (45):  8421-8425.  doi: 10.3969/j.issn.1673-8225.2010.45.015 Abstract ( 359 )   PDF (561KB) ( 562 )   Save BACKGROUND: Our previous studies indicted that bone marrow mesenchymal stem cells (BMSCs) modified by brain-derived neurotrophic factor (BDNF) gene could ameliorate the memory function of Alzheimer’s disease (AD) rat. OBJECTIVE: To observe the effect of BDNF gene-modified BMSCs transplantation on tau protein phosphorylation and beta-amyloid (Aβ) in the cerebral cortex and hippocampus, and neuron ultrastructure in the hippocampal CA1 region of AD model rat. METHODS: After AD models were established by Aβ stereotactic injection into lateral cerebral ventricle, BDNF modified and unmodified BMSCs were implanted into AD model. One month after transplantation, the expressions of total tau protein and tau hyperphosphrylation in cerebral cortex and hippocampus were detected using Western blotting method. Aβ 40 and Aβ 42 were detected by enzyme-linked immunosorbent assay, and the hippocampal CA1 neuron ultrastructures were observed via transmission electron microscope. RESULTS AND CONCLUSION: BDNF-modified BMSCs could decrease expression of total tau protein and tau hyperphosphrylation in the cerebral cortex and hippocampus and reduce Aβ 40 and Aβ 42 expression in the cerebral cortex and hippocampus. In AD model group, there were obvious degeneration of organells, such as disruption of rough endoplasmic reticulum, reduction of ribosome, mitochondrial swelling, blurred nuclear membrane. BDNF-modified BMSCs could reduce above-described changes. Its effect was more significant than unmodified BMSCs group. Related Articles | Metrics

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Influence of neural stem cell transplantation on the number of p75NGFR positive neurons of the basal forebrain and the ethology of an animal model of Alzheimer's disease with 192-IgG-saporin Pan Xue-bing, Long Da-hong, Luo Xiu-mei,Tu La-geng, Pan li, Wang Gui-ping 2010, 14 (45):  8426-8430.  doi: 10.3969/j.issn.1673-8225.2010.45.016 Abstract ( 291 )   PDF (717KB) ( 573 )   Save BACKGROUND: Neural stem cells (NSCs) can have a continuous amplification in vitro, have the reproductive activity and plasticity and can survive, migrate, differentiate and integrate into host central nervous system in adult life. OBJECTIVE: To analyze the effects of NSCs transplantation on the cholinergic p75NGFR positive neurons and behavior of the basal forebrain and behavior of the rat model of Alzheimer’s disease (AD) with lateral ventricle injection of 192-IgG-saporin. METHODS: A total of 24 Sprague Dawley rats were randomly divided into three groups: normal group, model group and transplantation group. A total of 10 new born Sprague Dawley mouse (< 24 hours) were used for isolation and culture of NSCs. 192-IgG-saporin was injected into the lateral ventricle of Sprague Dawley rats to establish AD animal model. Then, NSCs were transplanted in basal forebrain in the transplantation group. At four weeks, Y-maze test was performed. The changes of morphologic data and number of p75NGFR positive neurons were measured in basal forebrain by using image analysis. RESULTS AND CONCLUSION: About 1 month after 192-IgG-saporin injection, the number of p75NGFR-positive neurons at the lesion side of medial septal nucleus and vertical diagonal branch was significantly reduced in the model group (P < 0.01). However, the number of p75NGFR-positive neurons at the lesion side of medial septal nucleus and vertical diagonal branch was increased up to 74.85% and 71.66% in the transplantation group, and there were significant differences compared with the model group (P < 0.01). Y-maze test showed the abilities of learning and memory of transplantation group were improved (P < 0.05). The effects of learning and memory may be positively related with the number of p75NGFR neurons of the basal forebrain. These indicated that NSCs transplantation is effective in improving ability of learning and memory and can improve and protect p75NGFR positive neurons of the basal forebrain in 192-IgG-saporin-induced AD models. Related Articles | Metrics

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Brca-1 gene-regulated neural stem cells transplantation in treatment of cerebral infarction Fang Li-qun, Zhang Zhuo-bo 2010, 14 (45):  8431-8434.  doi: 10.3969/j.issn.1673-8225.2010.45.017 Abstract ( 262 )   PDF (373KB) ( 350 )   Save BACKGROUND: Recently, someone presumed that the proliferation of neural precursor cells and neural cells is regulated by Brca-1 gene. OBJECTIVE: To observe the effect of Brca-1 gene regulation of neural stem cell transplantation on Sprague Dawley rat models of acute ischemic cerebral infarction. METHODS: Sprague Dawley rat models of acute ischemic cerebral infarction were established according to Longa method. By stereotaxical method, phosphate buffered saline, routinely cultured neural stem cells and 10-5 mol/L 17 β-estradiol cultured neural stem cells were infused into the lateral ventricle of affected brain of rat models separately. Neurological impairment was evaluated at various time points using animal ethology score. Laser confocal microscopy was utilized to observe Nestin expression in neural stem cells. Cerebral infarction volume on cerebral ischemia reperfusion model rats was evaluated by 2, 3, 5-rihenyltetrazolium chloride (TTC) staining. The brain pathological changes were observed by the optical and electron microscope. Immunohistichemical staining was used to examine the expression of neuron specific enolase (NSE) and glial fibrillary acidic protein (GFAP). RESULTS AND CONCLUSION:  ① The recovery of neural function was better in the 17 β-estradiol group compared with routinely cultured group (P < 0.05). ② Laser confocal microscopy has revealed that fluorescence intensity was strongest at 4 days in the ischemia/reperfusion group and blank group, gradually weak at 7 day. The fluorescence intensity was strongest at 4 days in the 17 β-estradiol group, but the persistent high intensity was long, and the strong intensity was visible at 7 days. ③ The cerebral infarct volume was significantly shortened in the 17 β-estradiol group, and significant difference was detected compared with the ischemia/reperfusion and blank groups (P < 0.05). ④ Neurons were not swollen, with visible nuclei, even chromatin and a majority of normal blood capillary at 7 days following cell transplantation in the 17 β-estradiol group. ⑤ Positive expression of NSE and GFAP was greater in the 17 β-estradiol group compared with routinely cultured group. These suggest that the neuroprotective effect of neural stem cells cultured with estrogen transplantation group is better than routine neural stem cell transplantation group. Related Articles | Metrics

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Changes in vascular endothelial growth factor and angiogenesis in dogs with acute myocardial infarction following autologous bone marrow mesenchymal stem cells transplantation Wang Yong, Wu Ji-xiong, Fang Wu-wang, Lin Bing-lai, Rui Zu-qin 2010, 14 (45):  8435-8440.  doi: 10.3969/j.issn.1673-8225.2010.45.018 Abstract ( 326 )   PDF (2128KB) ( 473 )   Save BACKGROUND: Bone marrow mesenchymal stem cells (BMSCs) can be induced to differentiate into cardiomyocyte-like cells in vivo and in vitro. BMSCs transplantation in local region can promote angiogenesis, prevent ventricle reconstruction, and improve cardiac function, but precise mechanisms remain unclear. OBJECTIVE: To investigate vascular endothelial growth factor (VEGF) expression and angiogenesis in myocardial infarction zone following BMSCs cardiac transplantation in dogs. METHODS: Healthy hybrid dogs were randomly assigned to experimental and control groups. All dogs were used to establish models of acute myocardial infarction. At 1 and 2 hours following model induction, BrdU-labeled BMSC suspension was infused into four or five regions of myocardial infarction region in the experimental group, whereas an equal volume of Dulbecco’s modified Eagle’s medium was injected into the dogs of control group. At 4 weeks following transplantation, VEGF concentration in serum was determined using enzyme-linked immunosorbent assay (ELISA). Capillary density was detected using immunohistochemical staining. RESULTS AND CONCLUSION: On day 1, weeks 1, 2, 3 and 4 following transplantation, VEGF concentrations were increased in the experimental group compared with control group (P < 0.01). Moreover, VEGF concentrations were decreased over time in two groups (P < 0.01). Capillaries per unit area of the experimental group were significantly increased in infarct region compared with control group (P < 0.01). Results showed that after BMSCs transplantation, in myocardial infarct area, the concentration of VEGF is increased and promotes angiogenesis after myocardial infarction. Related Articles | Metrics

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Effects of human cytomegalovirus infection on expressions of Hoxb2 and Hoxb4 gene in the development process of cord blood erythroid progenitor cells Huang Mei-xian, Liu Wen-jun, Guo Qu-lian, Chen Jun-hong, Shi Han　 2010, 14 (45):  8441-8445.  doi: 10.3969/j.issn.1673-8225.2010.45.019 Abstract ( 332 )   PDF (399KB) ( 379 )   Save BACKGROUND: Human cytomegalovirus (HCMV) infection can damage the hematopoietic system, and even cause bone marrow failure. HCMV infection inhibited erythroid progenitor cell proliferation and differentiation, and whether the proliferation of erythroid progenitor cells associated with abnormal expression of genes? OBJECTIVE: To investigate the expressions of the Hoxb2 gene and Hoxb4 gene after the differentiation and proliferation of the hematopoietic stem cells to the colony forming erythroid progenitor cells (CFU-E) in vitro, which infected by HCMV and/or affected by all-trans retinoic acid (ATRA). METHODS: Cord blood was collected from fetal placenta umbilical vein of 12 cases. With the colony culture in vitro and the fluorescence quantity reverse transcriptase polymerase chain reaction method, HCMV-AD169 and (or) ATRA (6×10-8 mol/L) was used to intervene the CFU-E colony formation. The expressions of Hoxb2 and Hoxb4 genes on the differentiation progress of hematopoietic stem cells to CFU-E affected by HCMV and/or ATRA were observed in the blank, ATRA, HCMV-AD169, ATRA+HCMV groups at 3, 7 and 10 days.  RESULTS AND CONCLUSION: The quantity of Hoxb2 and Hoxb4 genes was expressed on day 3, obviously increased on day 7 and highest on day 10 in each group. Compared with the blank group, expressions of Hoxb2 and Hoxb4 genes were down-regulated obviously in the HCMV group. Compared with the HCMV group, expressions of Hoxb2 and Hoxb4 genes were obviously up-regulated in the HCMV+ATRA group (P < 0.05). Results suggest that abnormal expression of Hoxb2 and Hoxb4 gene induced by HCMV may play an important role in abnormal hematogenic damage. Hoxb2 and Hoxb4 gene were correlated to the process of in the proliferation and differentiation of erythroid progenitor cells. ATRA (6×10-8 mol/L) can up-regulate the expression of Hoxb2 and Hoxb4 gene significantly in normal erythroid progenitor cells, and those infected by HCMV. Related Articles | Metrics

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Intervention role of ground beetle on the expression of Type Ⅰ collagen mRNA in steroid-induced bone marrow mesenchymal stem cells Qi Zhen-xi, Li Shu-qiang, Yu Tao 2010, 14 (45):  8446-8449.  doi: 10.3969/j.issn.1673-8225.2010.45.020 Abstract ( 290 )   PDF (326KB) ( 338 )   Save BACKGROUND: The early pathological changes of steroid-induced avascular necrosis of femoral head may be related to the steroid-induced bone marrow mesenchymal stem cells (BMSCs) adipogenic differentiation. OBJECTIVE: To investigate the promoting effects of ground beetle drug-containing serum on osteogenic differentiation of BMSCs. METHODS: The 3rd generation of BMSCs was randomly divided into blank group, control group and Chinese medicine with high, moderate and low dose groups. The low-, moderate- and low-dose Chinese medicine groups were treated with various doses of medium (1 L medium contained 100 g drug-containing serum), with an additional dexamethasone till final concentration was 10-6 mol/L. The control group was subjected to medium containing saline serum, with an additional dexamethasone till the final concentration was 10-6 mol/L. The medium containing saline serum was added in the blank group, without dexamethasone. At 6 days following intervention, ossify markers Collagen I mRNA and alkaline phosphatase (ALP) expression in cells was determined. RESULTS AND CONCLUSION: Following 6 days of intervention, the intracellular ALP content and mRNA expression of collagen type I was significantly lower in the control group than the blank group, while was greater in the Chinese group than in the control group, and the differences were significant (P < 0.01). These suggest that mechanism of ground beetle to prevent and to cure the avascular necrosis of the femoral head is not only to improve the microcirculation, but also associates with the decrease in steroid-induced osteogenic differentiation of BMSCs. Related Articles | Metrics

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Culture and identification of endothelial progenitor cells from human umbilical cord blood in vitro Fang Li-jian, Song E, Luan Ying, Lu Cheng-wei, Yang Wei, Shi Hui, Bi Ming-chao 2010, 14 (45):  8450-8454.  doi: 10.3969/j.issn.1673-8225.2010.45.021 Abstract ( 309 )   PDF (685KB) ( 462 )   Save BACKGROUND: The method of traditional immunomagnetic beads sorting endothelial progenitor cells (EPCs) shows complicated operation, with high cost and low cell obtaining rate. Moreover, the proliferation and differentiation of EPCs are limited. OBJECTIVE: To elucidate a method for in vitro induction and identification of EPC from human cord blood monocytes (CBMC), to realize EPC transplantation, and to provide enough cell source for improving blood vessel function. METHODS: CBMCs were isolated by Percoll density gradient centrifugation from cord blood, in vitro induced to differentiate and amplified, and then identified by immunohistochemical and immunofluorescent staining and flow cytometry.  RESULTS AND CONCLUSION: During culture, the cells became spindle-shaped and displayed cobble-stone morphology with outgrowth. On day 7, immunostaining of adherent cells was positive for the cell markers CD31 and vWF. (83.0±4.3)% of attached cells were positive for the double marker DiI-acLDL/FITC-UEA-Ⅰ. The red fluorescence of DiI-acLDL-labeled EPCs lasted for over 6 weeks in vitro. On day 7, flow cytometric analysis showed positive staining of attached cell for CD34, CD133 and KDR (17.8±3.7)%, (22.1±4.4)% and (81.5±5.0)%, respectively. Results indicate that the mononuclear cells from CBMC differentiate into EPCs. It can differentiate into endothelial cells by in vitro amplification. Related Articles | Metrics

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Culture and cryopreservation of mouse bone marrow-derived dendritic cells Zhu Guo-hui, Weng Xiao-dong, Liu Xiu-heng, Kuang You-lin　 2010, 14 (45):  8455-8459.  doi: 10.3969/j.issn.1673-8225.2010.45.022 Abstract ( 386 )   PDF (369KB) ( 390 )   Save BACKGROUND: Dendritic cell is an ideal carrier of tumor antigen due to the presenting function and the promotion of T cell proliferation. How to obtain large numbers of dendritic cells is important for producing tumor vaccine. OBJECTIVE: To induce, culture, amplify and cryopreserve dendritic cells derived from mouse bone marrow, then compare the biological characters of cryopreserved dendritic cells with the fresh dendritic cells, than find an effective method to obtain and store large numbers of dendritic cells. METHODS: Dendritic cells from mouse bone marrow cells were induced, cultured and amplified in complete medium with recombinant mouse granulocyte-macrophage colony-stimulating factor (rmGM-CSF) (10 μg/L) and recombinant mouse interleukin 4 (rmIL-4) (5 μg/L). On day 6, the dendritic cells were frozen in complete medium with dimethyl sulphoxide. After thawing, lipopolysaccharide was added to induce the maturation. At last, large number of mature dendritic cells was obtained. Then the viability, morphology, dendritic cells markers and mixed lymphocyte reaction were compared between the thawed cells and fresh cells. RESULTS AND CONCLUSION: After thawing, the recovery rate of cells was (82.2±4.73)%. The survival cells became mature dendritic cells induced by lipopolysaccharide. Compared with fresh dendritic cells, there was no significant difference in morphology, dendritic cells markers and mixed lymphocyte reaction. Results suggest that there was no significant difference in biological characters between frozen-thawed dendritic cells and fresh dendritic cells. To store dendritic cells through cryopreservation can avoid repeating culture in different times and can obtain large numbers of dendritic cells. Related Articles | Metrics

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Related factors affecting peripheral blood CD34+ cell purification Bai Wen, Bai Bin, Wang Li-ming, Zhou Jian-jun, Zhang Cong, Liu Tao　 2010, 14 (45):  8460-8463.  doi: 10.3969/j.issn.1673-8225.2010.45.023 Abstract ( 362 )   PDF (328KB) ( 417 )   Save BACKGROUND: Hemopoietic stem cells have the potential of self replication and renewal. CD34+ cells have the marker of hemopoietic stem cells. OBJECTIVE: To analyze the related factors that affect the peripheral blood CD34+ cell purification. METHODS: From 90 cases of patients, the peripheral blood were collected, after human granulocyte colony stimulating factor (G-CSF) 5 μg/kg•d mobilizing for 1-3 days, using COBE machine mononuclear cells fluid 80-100 mL was collcected, the CD34+  stem cells were purified by Clini MACS. RESULTS AND CONCLUSION: The mean value of CD34+ cells was (1.73±1.15)×107 in 90 cases. Using flow cytometry, the positive rate of CD34+ cells was more than 80%. When the circulation blood liquid singly collected by COBE machine was 980- 1 100 mL, it was useful for CD34+ cells collection (P = 0.005). After mobilizing, when the white blood cell concentration was (16-21)×109/L, it was useful for CD34+ cells collection (P < 0.05);  when the general ratio of middle cells to lymphocytes was more than 11%, it was useful for CD34+ cell collection (P < 0.05).  When the concentration of blood platelet in mononuclear cells was less than 2 100×109/L, it was useful for CD34+ cell collection (P < 0.05); when the patient’s age was younger than 16 years, the number of collected CD34+ cells was high (P = 0.003). Moreover, the temperature of CD34+ cells, the magnetism marker, the eccentricity of treating cells, all could affect the CD34+ cells collection. Results indicate that the CD34+ cells purified by Clini MACS machine could fit the clinical need and keep good experiment stability and repeatability. To improve the CD34+ cells collection, the related factors which affect the peripheral blood CD34+ purification should be carefully considered. Related Articles | Metrics

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Isolation and culture of human submandibular gland stem/progenitor cells Wang Chun-yu, Huang Gui-lin, Zhang Ni-ni, Zhang Yue-rong, Song Qing-gao, Pan Guang-hua, Fang Ning 2010, 14 (45):  8464-8468.  doi: 10.3969/j.issn.1673-8225.2010.45.024 Abstract ( 303 )   PDF (594KB) ( 573 )   Save BACKGROUND: Recently, scholars have verified that salivary gland cells that have adult stem cell characteristics exist in salivary gland tissues. However, these stem cells mainly focus in animal salivary gland. There are a few studies concerning biological characteristics of human salivary gland stem cells. OBJECTIVE: To isolate and culture human salivary gland stem/progenitor cells in vitro, and to investigate the biological characteristics of these cells. METHODS: Human salivary gland stem/progenitor cells were harvested from submendubular glands of the legally abortion fetus for monoclonal culture. Epithelial cell marker cytokeratin 19 (CK19) and Laminin were analyzed by immunohistochemistry. Surface markers CD29, CD90.1 and CD117 expressions were detected by flow cytometric analysis. Growth curve of human salivary gland stem/progenitor cells was drawn, and proliferation ability in vitro was evaluated. RESULTS AND CONCLUSION: The human salivary gland stem/progenitor cells expressed intracellular Laminin and CK19. Flow cytometric analysis results revealed that the percentage of cells positive for CD90.1, CD29 and CD117 were 99.69%, 98.83% and 67.27%. The cells had perfect ability of proliferation, clonality and passage in vitro. These indicate that these cells from fetus submandibular glands have the characteristics of tissue stem cells. Related Articles | Metrics

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Establishing a rat model of intramyocardial stem cell transplantation without artificial ventilation Wei Feng, Zhang Jing, Wang Ting-zhong, Ni Ya-juan, Ma Ai-qun 2010, 14 (45):  8469-8472.  doi: 10.3969/j.issn.1673-8225.2010.45.025 Abstract ( 272 )   PDF (682KB) ( 424 )   Save BACKGROUND: Models of intramyocardial transplantation of stem cells in small experimental animals are often established with artificial ventilation by endotracheal intubation, in addition to cutting sternum or ribs. The operation is seriously wounded and complicated, which may impact on survival of models. OBJECTIVE: To establish a model of intramyocardial transplantation of stem cells in normal and infarcted rats without artificial ventilation. METHODS: Sprague Dawley rats were assigned to two groups. Myocardial infarction group: rats, following successful establishment of myocardial infarction model, received bone marrow mesenchymal stem cells (BMSCs) transplantation. For each rat, BMSCs were injected into surrounding sites of the infracted region by five points. In normal group, BMSCs with the same quantity were injected into epicardial sites in the left ventricle anterior wall by the same method. Rats in each group were killed 4 days after transplantation, and hearts were obtained for frozen sections. The distribution and survival of BMSCs labeled with green fluorescent protein (GFP) were observed under fluorescence microscope. Immunofluorescence staining was used to examine the cardiac-specific proteins expression on BMSCs. RESULTS AND CONCLUSION: The survival rate was 80% in transplantation model in myocardial infarction group, and 93% in normal group. 4 days after transplantation, a lot of BMSCs, which showed zonal distribution with arranging in parallel with myocardial fibers, could be observed in the transplantation area. Furthermore, Connexin43 and myosin heavy chain MYH were also detected on BMSCs. Results indicate that using this method, a model of intramyocardial transplantation of stem cells in rat can be established simply and effectively without using artificial ventilation. Related Articles | Metrics

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A simple and effective method for single cells separation Huang Ming-wei, Lu Yun-fei, Shen Gui-xin, Li Tao　 2010, 14 (45):  8473-8475.  doi: 10.3969/j.issn.1673-8225.2010.45.026 Abstract ( 527 )   PDF (329KB) ( 707 )   Save BACKGROUND: Research of stem cell or cancer stem cell at single cell level would be popularity in the near further. Many researchers stop going ahead when they have no idea to obtain lots of single cells in their study. A simple and effective method for single cell separation would be a foundation of exactly and quantitative study at single cell level. OBJECTIVE: To introduce a simple and effective method for single cell separation. METHODS: The separation method was improved based on micromanipulate and single cells were separated by using special separation equipment which makes up of micropipettor and the smallest intravenous needle. Success rates of separation were evaluated by separated staining of single cells. RESULTS AND CONCLUSION: Success rate of single cells separation was 96.5%. The method has many advantages: material was easily to find; the manipulate method was simple, visual, reliable and easy to popularization and application; high success rate. Those single cells which had been separated can be used for further study directly. Related Articles | Metrics

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Mesenchymal stem cells for treating autoimmune diseases and its oncogenicity of cell biotherapy Huang Jin-qi, Lin Yan-juan 2010, 14 (45):  8478-8482.  doi: 10.3969/j.issn.1673-8225.2010.45.028 Abstract ( 410 )   PDF (980KB) ( 449 )   Save BACKGROUND: Mesenchymal stem cells (MSCs) can participate in regulating communication signal between immune cells (antigen presenting cell, T cell, B cell, natural killer cell and so on) and induce autoantigen-specific immune tolerance or immunological unresponsiveness by secreting a variety of cytokines and cell-cell contact. This therapeutic strategy makes great significance to auto-immune disease. Some scholars began to try and validate this strategy on autoimmune disease animal models as well. OBJECTIVE: To understand application progress of MSCs in the field of auto-immune disease. METHODS: The first author searched PubMed database (http://www.ncbi.nlm.nih.gov/PubMed) and OVID database (http://gateway.ovid.com) for literatures concerning MSC immune characteristics, MSCs as a cell therapy manner for auto-immune disease and MSC oncogenicity published from 2005 to 2010. Key words were “Mesenchymal stem cell, immune characteristics, cell-based therapy, autoimmune disease, oncogenicity”. Duplicate articles were excluded. Finally, 31 articles were selected. RESULTS AND CONCLUSION: Auto-immune characteristics of MSCs and directional differentiation characteristics of stem cells made them distinguished from traditional immunosuppressive drugs. As a new biotherapy, MSCs open a new way for treating auto-immune disease, besides hematopoietic stem cells. Oncogenicity should be further identified and effectively prevented, which may be a main study direction in the field of MSCs. MSC for autoimmune diseases should be strictly kept. There is not enough evidence for replacing the traditional immunosuppressants. Related Articles | Metrics

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Induced differentiation of bone marrow mesenchymal stem cells into chondrocytes Zhang Mei, Lü Guo-feng 　 2010, 14 (45):  8483-8486.  doi: 10.3969/j.issn.1673-8225.2010.45.029 Abstract ( 347 )   PDF (327KB) ( 425 )   Save BACKGROUND: Bone marrow mesenchymal stem cells (BMSCs) affected by different environmental and biological factors in vitro can transform into cartilage cells, which is the focus of cartilage tissue engineering study in recent years. OBJECTIVE: To summarize the effects of cytokines, stress stimulation, three-dimensional structure on BMSCs differentiation into cartilage cells. METHODS: The databases of China National Knowledge Infrastructure and Pubmed were searched for the articles about BMSCs differentiation into chondrocytes published from January 2001 to June 2010. The key words were “bone marrow mesenchymal stem cells, chondrocyte, differentiation”, which used by inputting in titles and abstracts. The articles addressing BMSCs differentiation into chondrocytes were included. Those in the same field published recently or in authorized journals were included. There were 109 articles after the initial survey. Totally, 26 articles were included in accordance with inclusion criteria. RESULTS AND CONCLUSION: Cytokines, stress stimulation, three-dimensional structure effects on BMSCs differentiation into cartilage cells was significant. The conditions for optimizing these factors can be more easily induced to differentiate into chondrocyte phenotype. With the deep understanding of BMSCs differentiation into cartilage cells, the application of these factors will be more extensive. Related Articles | Metrics

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Reprogramming of induced pluripotent stem cells Bian He-tao, Huang Wei, Li Shi-yong 2010, 14 (45):  8487-8490.  doi: 10.3969/j.issn.1673-8225.2010.45.030 Abstract ( 361 )   PDF (322KB) ( 472 )   Save BACKGROUND: Although induced pluripotent stem cells (iPSCs) have similar morphological, epigenetic and gene expression characteristics as embryonic stem cells (ESCs), this research is at a very early stage and many fundamental questions remain such as security and efficiency. OBJECTIVE: To review empirical study of iPSCs. METHODS: A computer-based online search of Medline, Ovid, CNKI, and EBSCO databases was undertaken for the literature of iPSCs. The key words were “induced pluripotent stem cells, embryonic stem cells, somatic cells, reprogramming, induction, transcription factor”. RESULTS AND CONCLUSION: iPSCs of specific genes, mainly through import, reprogram somatic cells. Its specific genes include Oct 4, Sox2, c-Myc, Klf4, Nanog, Lin-28. These exogenous transcription factors can activate endogenous Oct4 and Sox2 expression, which contribute to form a network of self-regulation and to maintain iPSCs pluripotent. However, the specific mechanism of reprogramming remains unclear. Related Articles | Metrics

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Research progress in the relationship between cell immortalization and carcinogenesis Wu Di, Jia Yong-feng, Wu Yan 2010, 14 (45):  8491-8494.  doi: 10.3969/j.issn.1673-8225.2010.45.031 Abstract ( 882 )   PDF (322KB) ( 1062 )   Save BACKGROUND: Many differences and connections have been observed between immortalized cells and tumor cells in the level of gene, protein and phenotypic types. It was some different opinions that exist in the relationship between the two cell types. OBJECTIVE: To analyze the correlation between immortalized cells and tumor cells, and to summarize research progress and perspective of studying tumor cell production. METHODS: Pubmed and SpringerLink databases were searched by computer for articles published from January 2001 to January 2010. The key words were “cellular immortality, cancer mechanism”. China National Knowledge Infrastructure database was searched by computer for articles published from January 2001 to January 2010. The key words were “cellular immortality, cancer mechanism”. RESULTS AND CONCLUSION: A total of 95 relevant articles were collected including 35 Chinese articles and 60 English articles. Finally, 41 articles were used after the earlier publishers and similar repeated studies were excluded. Immortalized cells are not tumor cells. It is generally believe that cells immortalized passages is a necessary step in the process of malignant transformation of cells, if just as it said so, the culture of tumor cells should be easy. In fact, in vitro culture of tumor cells is very difficult; some scholars have questioned the relationships between the two. At present, the theory on the arising of tumor cells exists as follows: aneuploidy hypothesis, DNA immortalized chain hypothesis, cancer stem cell hypothesis and so on. The further study of the relationships between the two is helpful to the application of immortalized cells and beneficial to tumor treatment. Related Articles | Metrics

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PSA-NCAM and neurogenesis in the rat hippocampus Li Zhong 2010, 14 (45):  8495-8498.  doi: 10.3969/j.issn.1673-8225.2010.45.032 Abstract ( 346 )   PDF (324KB) ( 441 )   Save BACKGROUND: Numerous animal studies have shown that the brain of mature animals contains regeneration field of neural cells. New neural cells produced by hippocampal dentate gyrus can migrate to the granular layer, and differentiate into functional neural cells. OBJECTIVE: To provide new ideas for the treatment of brain injury by studying the feature of neural stem cells and the affected factors of the new cells differentiation, migration and survival. METHODS: The computer was applied to retrieve the articles in CNKI periodical full-text database and PubMed database published from 1996 to 2009. Words for retrieve were “Neural stem cells, PSA-NCAM, cerebral infarction”. Articles concerning PSA-NCAM and neurogenesis in the rat hippocampus were included. The literature of irrelevant purpose and repetitive content was excluded, and then 48 literatures were retained to summarize. RESULTS AND CONCLUSION: Neurogenesis continues in the hippocampal dentate gyrus, the subventricular zone of the lateral ventricle and olfactory bulb. These regions contain abundant neural stem cells, which have the ability of proliferation, differentiation and regeneration. The central nerve has many cytokines that can promote proliferation, differentiation and migration of neural stem cells, including PSA-NCAM. Related Articles | Metrics

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Correlation of CD4+CD25+ regulatory T cells and acute graft versus host disease in allogenic hematopoietic stem cells transplantation Fei Xiao-li, Liu Lin 2010, 14 (45):  8499-8502.  doi: 10.3969/j.issn.1673-8225.2010.45.033 Abstract ( 322 )   PDF (317KB) ( 358 )   Save BACKGROUND: CD4+CD25+  regulatory T cells are one of the important subsets of regulatory T cells, playing an important role in inducing transplantation tolerance. OBJECTIVE: To summarize characteristics, immunoloregulation action mechanism of CD4+CD25+  regulatory T cells and its correlation with acute graft versus host disease. METHODS: We retrieved PubMed and Medline databases for articles published from January 1990 to February 2010, Vip Database for articles published from January 2000 to February 2010, and Google for articles concerning CD4+CD25+ regulatory T cells and acute graft versus host disease. RESULTS AND CONCLUSION: CD4+CD25+  regulatory T cells play an important role in acute graft versus host disease following allogenic hematopoietic stem cells transplantation. CD4+CD25+  regulatory T cells not only effectively prevent and treat acute graft versus host disease, while retain graft versus leukemia effect. A detailed study found that CD4+CD25+  regulatory T cells are an important experimental diagnostic indicator of acute graft versus host disease for early phase risk forecast, and possibly prevent and control the occurrence of acute graft versus host disease through regulating the level of CD4+CD25+  regulatory T cells in vivo. However, CD4+CD25+  regulatory T cells applied in clinic still have some issues to be resolved, such as what is the specific cell surface marker of CD4+CD25+ regulatory T cells, and how to improve the activity of CD4+CD25+  regulatory T cells in the human body and how to play its immunosuppressive function abundantly.   Related Articles | Metrics

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Effects of traditional Chinese medicine in the induction of stem cell differentiation into cardiomyocytes Wang Dong-jin, Shi Guang-fei, Jiang Hong, Yu Hong-song 2010, 14 (45):  8503-8506.  doi: 10.3969/j.issn.1673-8225.2010.45.034 Abstract ( 355 )   PDF (325KB) ( 870 )   Save BACKGROUND: Classical stem cell inducer due to its cytotoxicity only has been utilized in stem cell vitro experiment, which provides a challenge for elevating the therapeutic effect of stem cell transplantation. More and more studies have verified that traditional Chinese medicine as a new stem cell inducer can induce the differentiation of embryonic stem cells and bone marrow mesenchymal stem cells (BMSCs) into cardiomyocytes. This study group engaged in myocardial stem cell research for a long term. The alkaloid ligustrazine extracted from Szechwan Lovage Rhizome has successfully induced the differentiation of cardiac stem cells into cardiomyocytes in vitro. OBJECTIVE: To summarize the advance in traditional Chinese medicine stem cell inducer and to provide a basis for the efficiency of stem cell differentiation into cardiomyocytes during cardiovascular diseases stem cell transplantation. METHODS: Key words were “traditional Chinese medicine, stem cells, cardiomyocytes”. Foreign Medical Journal Service (www.kjmed.com.cn), Chinese journal full-text database, China Doctor Dissertations Full-text Database and China National Knowledge Infrastructure were searched for articles on the differentiation of stem cells into cardiomyocytes induced by traditional Chinese medicine published from 2005 to 2009. The repetitive studies were excluded. The retrieved literatures contained original articles, thesis and reviews. RESULTS AND CONCLUSION: A total of 30 articles were included for this review, including 14 Chinese articles and 16 English articles. Results exhibited that traditional Chinese medicine as a new stem cell inducer not only effectively induced stem cell differentiation into cardiomyocytes, but also was characterized by no side or adverse effects. Therefore, it is hopeful to use in clinical stem cell therapy. It is new for traditional Chinese medicine to induce stem cell differentiation into cardiomyocytes. With deep research, more and more traditional Chinese medicine inducer will be found. Related Articles | Metrics

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Induced differentiation of mesenchymal stem cells into hepatocyte-like cells Chen Jun, Liu Yu-xia, Jiang Wen-hua 2010, 14 (45):  8507-8511.  doi: 10.3969/j.issn.1673-8225.2010.45.035 Abstract ( 277 )   PDF (351KB) ( 391 )   Save BACKGROUND: At present, many experiments have shown that mesenchymal stem cells (MSCs) can differentiate into hepatocyte-like cells or hepatocytes in vitro and in vivo. This makes it possible for MSCs in treatment of liver diseases.  OBJECTIVE: To conclude and analyze the methods, mechanism and existing problems of MSCs differentiation into hepatocyte-like cells.  METHODS: We searched PubMed Database using computer for articles published from January 2000 to December 2009. The key words were “mesenchymal stem cells, hepatocyte, differentiation”. Vip Database was retrieved for articles published from January 2000 to December 2009. The key words were “mesenchymal stem cells, hepatocyte, induced differentiation”. Articles concerning induced differentiation of MSCs into hepatocytes, and those published recently or in authorized journals were included. RESULTS AND CONCLUSION: A total of 146 articles addressing induced differentiation of MSCs into hepatocytes were collected, and 31 articles were included according to inclusion criteria. MSCs can be induced to differentiate into hepatocytes in vitro and under hepatic pathological condition. Its action mechanism is that cytokines via specific cell signaling pathway affected cell nucleus, started or closed corresponding gene, expressed specific protein, and induced the differentiation of MSCs into hepatocytes under suitable cytokine combination. With the development of study, this makes it possible for MSCs in treatment of liver diseases, but still requires further improvement. Related Articles | Metrics

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Autologous bone marrow mononuclear cells transplantation in treatment of severe lower limb ischemia in 56 cases in the same institute: One-year follow up Wang Wei, Liu Chang-jian, Qiao Tong, Liu Chen, Huang Dian 2010, 14 (45):  8512-8515.  doi: 10.3969/j.issn.1673-8225.2010.45.036 Abstract ( 378 )   PDF (310KB) ( 472 )   Save BACKGROUND: Autologous bone marrow mononuclear cell transplantation for treatment of lower limb ischemia has obtained satisfactory short-term curative effects, but lacks of long-term follow up. In particular, few reports have addressed peripheral artery disease patients with severe lower limb ischemia. OBJECTIVE: To investigate the efficacy of autologous bone marrow mononuclear cells transplantation in treatment of severe lower limb ischemia in 4 weeks and 1 year follow up. METHODS: From January 2005 to January 2009, 56 patients (59 limbs) with severe lower limb ischemia were treated. 300 mL bone marrow blood was extracted from patients’ ilium to separate and prepare autologous bone marrow mononuclear cells. The transplant part was from occlusion site of middle and lower extremity artery trunk. According to the way of arterial ambulation, stem cell suspension was made and injected once every 1.0-2.0 cm (each 1 mL). The local transplantation of lower limb ischemia muscle was performed. All patients received cell transplantation only once. The amount of transplanted bone marrow mononuclear cells was (0.31-29.46)×109 (mean 10.93×109). RESULTS AND CONCLUSION: All patients were followed up for one year. After 4 weeks of implantation, the results of visual analogue scale, maximum walking distance, ankle brachial index, TcPO2 were superior at 4 weeks and 1 year following surgery compared with the preoperative results (P < 0.05). After one year of implantation, angiography revealed 28.8% (17/59) effective rate. No related complication was observed in patients after transplantation. Related Articles | Metrics

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Autologous bone marrow mesenchymal stem cells transplantation for early avascular necrosis of the femoral head in 44 cases Zhu Bing, Sun Tian-sheng, Zhou Jun,Yao Jian-hua, Wu Jun, Chang Hong-xing, Ren Da-jiang 2010, 14 (45):  8516-8520.  doi: 10.3969/j.issn.1673-8225.2010.45.037 Abstract ( 322 )   PDF (293KB) ( 457 )   Save BACKGROUND: Avascular necrosis of the femoral head (ANFH) is deficient in mesenchymal stem cells and their function for osteogenesis is lower than normal. The sclerotic bands affect bone repair. It is necessary that detailed result analysis of autologous bone marrow mesenchymal stem cells transplantation with core decompression that can improve blood transport and contribute to bone repair to early stage of ANFH. OBJECTIVE: To analyze results of follow up for early ANFH after autologous bone marrow mesenchymal stem cells transplantation and core decompression. METHODS: From May 2005 to September 2008, forty-four patients with early ANFH were enrolled. All 76 hips were in the stage of 1-2 of ARCO staging system. All enrolled patients received concentrated autologous bone marrow stem cell injection and combined core decompression. ARCO1 patients were subjected to stem cell suspension injection, and ARCO2 patients were subjected to core decompression following transplantation. Harris scoring was used to evaluate the outcomes. RESULTS AND CONCLUSION: Till March 2009, follow up was performed (22.3±4.2) months. Pain relief and function improved in 66 hips (86.9%); another 10 hips collapsed to stage 3-4 and total hip arthroplasty was performed in 3 cases. Results indicate that it is an effective and simple procedure for early ANFH using autologous bone marrow mesenchymal stem cells transplantation and core decompression. According to cytopathology of ANFH, our method is more reasonable than other procedures. Better clinical results would be achievable when carrying out in larger scale. Related Articles | Metrics

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Autologous bone marrow mesenchymal stem cells transplantation for end-stage liver disease in 39 patients He Jin-qiu, Pan Xing-nan, Wang Chong-guo, Yang Wen-long, Xiong Mo-long, Tu Ming-han,Xiong Zhi-qun, Yang Ling-ling1 2010, 14 (45):  8521-8525.  doi: 10.3969/j.issn.1673-8225.2010.45.038 Abstract ( 329 )   PDF (344KB) ( 759 )   Save Related Articles | Metrics

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Autologous peripheral blood mononuclear cells transplantation in treatment of 30 cases of critical limb ischemia: 3-year safety follow-up Wen Jin-chao, Huang Ping-ping 2010, 14 (45):  8526-8530.  doi: 10.3969/j.issn.1673-8225.2010.45.039 Abstract ( 344 )   PDF (312KB) ( 561 )   Save BACKGROUND: Stem cell therapy for vascular diseases has been a hot research point. At present, no reports have addressed diagnostic criteria or long-term safety. OBJECTIVE: To assess safety, efficacy and feasibility of the application of autologous transplantation of peripheral blood stem cells (PBSC) in the treatment of critical limb ischemia (CLI). METHODS: A total of 60 patients with CLI (30 cases of diabetic foot, 22 cases of atherosclerosis obliterans and 8 cases of thromboangiitis obliterans) were enrolled and randomized to the transplant group and control group. In the transplant group, the patients received subcutaneous injection of recombinant human granulocyte colony-stimulating factor (G-CSF) (600 μg/d) for 5 days to mobilize stem/progenitor cells, and their peripheral blood mononuclear cells were collected and transplanted by multiple intramuscular injections into ischemic limbs. All patients were followed up after at least 3 months, but those in the transplant group were at least 3 years. RESULTS AND CONCLUSION: The main manifestations, including lower limb pain and ulcers, were significantly improved in patients of the transplant group. The results of laser Doppler flowmetry showed that blood perfusion of lower limbs increased from (0.42±0.13) to (0.59±0.12) perfusion units (P < 0.001). Mean ankle-brachial pressure index was increased from (0.47±0.22) to (0.59±0.27) (P < 0.001). A total of 28 of 40 limb ulcers (70.0%) of transplanted patients were completely healed after cell transplantation, whereas only 26.8% of limb ulcers (11 of 41) were healed in the control patients (P=0.012). Angiographic scores were significantly improved in the transplant group compared with the control group (P = 0.002). One patient received a lower limb amputation in the transplanted patients. In control group, five control patients received a lower limb amputation (P = 0.005). No adverse effects specifically related to cell transplantation were observed in the transplant group at least 3 years after treatment. These results indicate that blood stem cell transplantation standard scheme for CLI is simple, safe and effective. Related Articles | Metrics

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Effects of interleukin-15 on proliferation of children’s myelodysplastic syndrome hematopoietic stem/progenitor cells Cheng Han-rong, Ye Zhong-lü, Chen Ming-zhen 2010, 14 (45):  8531-8534.  doi: 10.3969/j.issn.1673-8225.2010.45.040 Abstract ( 365 )   PDF (317KB) ( 368 )   Save BACKGROUND: Interleukin (IL)-15 is a member of hematopoietic cytokine superfamily. It may stimulate the proliferation of the myelodysplastic syndrome (MDS) hematopoietic stem/progenitor cells. OBJECTIVE: To investigate the effects of IL-15 on proliferation of hematopoietic cells in MDS child. METHODS: Cell-counting, MTT-inhibitory test were used to examine the inhibitory effect of IL-15 (0, 10, 20, 50, 100, 200 µg/L) on the proliferation of MDS CD34+ cells in 18 children aged 1-14 years to find out the peak concentration of IL-15. IL-15 at peak concentration served as experimental group, whereas those without IL-15 as control group. 12-day culture was done to understand optimal proliferation time of cells. RESULTS AND CONCLUSION: At day 8, CD34+cells cultured in vitro grew well. With increased IL-15 concentration, living cells number increased as well. When IL-15 was 100 µg/L, its proliferation status was the best, but when IL-15 was 200 µg/L, its proliferation status was below the mark. At day 8, the inhibitory rate of IL-15 on CD34+ cells was the lowest. When IL-15’s concentration was between 0 and 100 µg/L. With increased IL-15’s concentration, the inhibition decreased progressively. When IL-15 was above 100 µg/L, the inhibition reinforced on the contrary. These indicate that IL-15 can accelerate MDS bone marrow CD34+ hematopoietic stem/progenitor cell proliferation in a dose-and time-dependent manner Related Articles | Metrics

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Transplantation of autologous bone marrow mesenchymal stem cells after culture via hepatic artery for one patient with decompensated cirrhosis Jiao Hong-liang, Yang Bo, Guan Fang-xia, Li Jian-bin, Zhan San-hua, Du Ying, Hu Xiang, Chi Lian-kai, Liang Shuo, Shi Xin-yi 2010, 14 (45):  8535-8538.  doi: 10.3969/j.issn.1673-8225.2010.45.041 Abstract ( 346 )   PDF (362KB) ( 541 )   Save BACKGROUND: Bone marrow mesenchymal stem cells (BMSCs) in a specific environment can divide into hepatic stem cells and liver cells, which can participate in repair and reconstruction of liver structure and function. OBJECTIVE: To explore the safety, feasibility and therapeutic effect of autologous BMSCs after culture transplantation via hepatic artery in treatment of cirrhosis. METHODS: One patient with cirrhosis received autologous bone marrow mononuclear cell transplantation. Bone marrow mononuclear cells were isolated from autologous bone marrow and purified in vitro, and then cultured after 4 days. The stem cells were transplanted into the liver via hepatic artery. At 4 week after transplantation, serum albumin (ALB), cholinesterase (CHE), prothrombin activity (PTA), total bilirubin level (TBil), alanine aminotransferase (ALT), aspartate aminotransferase (AST), prothrombin time (PT), fibrinogen changes and complications and prognosis were observed. RESULTS AND CONCLUSION: Numbers of BMSCs were significantly increased after culture. The index changes were respectively observed before and after transplantation. Pre-transplant: ALB, CHE, PTA, ALT, AST, PT, and fibrinogen were respectively 29. 43 g/L, 2 378.5 U/L, 47. 4%, 112.78 U/L, 79.36 U/L, 17.91 s, 2.01 g/L; 4 week after transplantation: 33.30 g/L,    2 866. 5 U/L, 55. 8%, 79.01U/L, 56.37 U/L, 16.26 s, and 2.35 g/L. No adverse event occurred following transplantation. Results suggest that after transplantation of autologous bone marrow, the liver function of patients was significantly improved. This method was safe and effective in the treatment of patients with decompensated cirrhosis. It can be used as a clinical treatment in patients with middle and advanced stage cirrhosis. Related Articles | Metrics

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Construction of adenovirus vectors carrying VEGF121-FLAG and hrGFP-1 and their expressions in bone marrow stromal stem cells Liu Dan-ping, Li Chen, Hu Liang, Wang Guo-xian 2010, 14 (45):  8539-8543.  doi: 10.3969/j.issn.1673-8225.2010.45.042 Abstract ( 269 )   PDF (295KB) ( 844 )   Save BACKGROUND: Vascular endothelial growth factor (VEGF) can promote angiogenesis, and has been extensively used in treatment of bone defect. However, few studies have addressed its isomer VEGF121. OBJECTIVE: To construct adenovirus vector carrying VEGF121-FLAG and humanized Renilla reniformis green fluorescent protein 1(hrGFP-1) and observe its expression in bone marrow stromal stem cells (BMSCs). METHODS: Using polymerase chain reaction technique, VEGF121 gene contained in the plasmid of pTG19T-VEGF121 was used to remove termination codon. NotI and Xho I restriction sites were added before and after gene sequence. Obtained gene subclone was moved onto pMD19-T plasmid. The pMD19-T-VEGF121 and pShuttle-CMV-IRES-hrGFP-1 plasmids underwent double enzymatic digestion. Small fragment and big fragment were retrieved utilizing gel. Subsequently, coupled reaction was conducted to complete the construction of shuttle plasmid. After measuring virus titer, BMSCs were transfected and the fluorescence intensity was observed under fluorescence microscope. RESULTS AND CONCLUSION: Recombinant adenovirus plasmid was successfully constructed by enzymatic digestion determination and gene sequence. Fluorescence microscope has shown that BMSCs transfected with recombinant adenovirus presented significantly green fluorescence expression. Thus, adenovirus vector carrying VEGF121-FLAG and hrGFP-1 gene can express in eukaryotic cells, which can be used for gene therapy for ischemic disease. Related Articles | Metrics

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Research and application of human adipose tissue-derived stromal cells Sun Jian-hua, Liu Jie, Zhao Guo-qing, Hou Ling, Ding Juan 2010, 14 (45):  8544-8550.  doi: 10.3969/j.issn.1673-8225.2010.45.043 Abstract ( 285 )   PDF (399KB) ( 510 )   Save BACKGROUND: Human adipose tissue-derived stromal cells (ADSCs) possess exert proliferation and multi-directional ability. As a novel stem cell, it has been widely utilized in tissue engineering and plays an important role in biological and potential therapeutic applications. OBJECTIVE: To review the research progress, applications and existing problems of human ADSCs in tissue engineering and cell therapy by retrieving relevant publications. METHODS: PubMed and CNKI databases were undertaken to identify the relevant articles published from January 1960 to January 2009 with the key words of “human adipose tissue-derived mesenchymal cells, isolation, differentiation, immune phenotype, application” both in English and Chinese. The articles relate to biological characteristics and applications of ADSCs were selected. In the same field, the documents published earlier or in the authoritative journals were preferred, and the repetitive studies were excluded. RESULTS AND CONCLUSION: A total of 81 documents were searched by computer, and 57 references were included in the final analysis. The results demonstrated that, human ADSCs share many characteristics, including the high proliferative potential and exhibiting the exert ability to undergo multilineage differentiation under appropriate conditions. Human ADSCs can not only utilize for tissue repairing, but also for cell immune modulation and gene therapy. However, there are still problems in its application. With the development of research on human ADSCs, their biological characteristics will be revealed, and their application in tissue repairing, cell therapy, transplantation, as well as gene therapy must be hold a great promise. Related Articles | Metrics