Rat bone marrow mesenchymal stem cells expressing brain-derived neurotrophic factor were successfully obtained using a gene transfection method, then intravenously transplanted into rats with spinal cord injury. At 1,...Rat bone marrow mesenchymal stem cells expressing brain-derived neurotrophic factor were successfully obtained using a gene transfection method, then intravenously transplanted into rats with spinal cord injury. At 1,3, and 5 weeks after transplantation, the expression of brain-derived neurotrophic factor and neurofilament-200 was upregulated in the injured spinal cord, spinal cord injury was alleviated, and Basso-Beattie-Bresnahan scores of hindlimb motor function were significantly increased. This evidence suggested that intravenous transplantation of adenovirus- mediated brain-derived neurotrophic factor gene-modified rat bone marrow mesenchymal stem cells could play a dual role, simultaneously providing neural stem cells and neurotrophic factors.展开更多
We have shown previously that high-efficient gene transfer can be attained in primary hematopoietic cells using liposome-mediated gene transfer strategy. In order to examine the stability of gene expression mediated b...We have shown previously that high-efficient gene transfer can be attained in primary hematopoietic cells using liposome-mediated gene transfer strategy. In order to examine the stability of gene expression mediated by this gene transduction protocol, we observed the expression of marker gene in vivo by using bone marrow transplantation (BMT) to engraft lethally irradiated mouse with the genetically modified hematopoietic cells. The results showed that the mouse transplanted with appropriated number of transduced cells remained alive andhealthy. The PCR analysis and G418 selection of the spleen colonies and bone marrow cells isolated from lethally irradiated animals 15 days and 30 days after injection of genetically modified bone marrow cells showed that the progeny cells of the transduced hematopoietic stem cells still contained and expressed the transduced genes, suggesting that the hematopoietic system is at least partially re-constructed by the stem cells with marker gene and that the stable expression of foreign genes in vivo can be attained by using this easy and harmless transduction protocol. These findings provide experimental basis for clinician to further investigate the biology of marrow reconstruction and the mechanism of leukemia relapse after BMT.展开更多
Previous studies showed that tyrosine hydroxylase or neurturin gene-modified cells transplanted into rats with Parkinson＇s disease significantly improved behavior and increased striatal dopamine content. In the prese...Previous studies showed that tyrosine hydroxylase or neurturin gene-modified cells transplanted into rats with Parkinson＇s disease significantly improved behavior and increased striatal dopamine content. In the present study, we transplanted tyrosine hydroxylase and neurturin gene-modified bone marrow-derived mesenchymal stem cells into the damaged striatum of Parkinson＇s disease model rats. Several weeks after cell transplantation, in addition to an improvement of motor function tyrosine hydroxylase and neurturin proteins were up-regulated in the injured striatum, and importantly, levels of dopamine and its metabolite 3,4-dihydroxyphenylacetic acid increased significantly. Furthermore, the density of the D2 dopamine receptor in the postsynaptic membranes of dopaminergic neurons was decreased. These results indicate that transplantation of tyrosine hydroxylase and neurturin gene-modified bone marrow-derived mesenchymal stem cells increases dopamine synthesis and significantly improves the behavior of rats with Parkinson＇s disease.展开更多
Adult, male, Sprague-Dawley rats were injected with granulocyte-macrophage colony-stimulating factor-transfected bone marrow stromal cells （GM-CSF-BMSCs） into the ischemic boundary zone at 24 hours after onset of mi...Adult, male, Sprague-Dawley rats were injected with granulocyte-macrophage colony-stimulating factor-transfected bone marrow stromal cells （GM-CSF-BMSCs） into the ischemic boundary zone at 24 hours after onset of middle cerebral artery occlusion. Results showed reduced infarct volume, decreased number of apoptotic cells, improved neurological functions, increased angiogenic factor expression, and increased vascular density in the ischemic boundary zone in rats that underwent GM-CSF-BMSCs transplantation compared with the BMSCs group. Experimental findings suggested that GM-CSF-BMSCs could serve as a potential therapeutic strategy for ischemic stroke and are superior to BMSCs alone.展开更多
Objective： To explore the survival and migration of bone mesenchymal stem cells transplantated in intervertebral disc of rabbits and expression of the exogenic genes. Methods. Thirty-two rabbits were used, A randomiz...Objective： To explore the survival and migration of bone mesenchymal stem cells transplantated in intervertebral disc of rabbits and expression of the exogenic genes. Methods. Thirty-two rabbits were used, A randomized block design was used and discs in the same rabbit were one block,the lumbar discs from L2-3 to L5-6 were randomly divided into blank group, saline group, cell transplantation group Ⅰand cell transplantation group Ⅱ. The fluorescence microscopy was used to determine the fluorescence of the maker protein GFP and DNA-PCR was used to analyze the copies of DNA of neomycin-resistant gene at 1, 3, 6, months after transplantation. Results： There was fluorescence in cell transplantation group Ⅰ and Ⅱ and none in blank group, saline group at 1, 3, 6 months after transplantation. In cell transplantation groups,the fluorescent distribution was more scatter with time, but no significant difference between cell groups Ⅰ and Ⅱ. The test of neomycin resistant gene expressed in cell transplantation group Ⅰ and Ⅱ and quantitative analysis showed that there was no significant difference between the cell groups Ⅰ and Ⅱ （P〉0.05）. Conclusion： The transplanted bone mesenchymal stem cells can survive, migrate and the transfer genes can express efficiently, it suggests that the BMSC therapy may be effective to prevent and treat intervertebral disc degeneration.展开更多
Objective: To study the efficacy of combined use of a new grafting material, new reconstituted bone xenograft (NRBX) and free periosteal graft in repair of segmental bony defects. Methods: NRBX was made by combining r...Objective: To study the efficacy of combined use of a new grafting material, new reconstituted bone xenograft (NRBX) and free periosteal graft in repair of segmental bony defects. Methods: NRBX was made by combining recombi- nant human BMP2(rhBMP2) and an antigen-free bovine cancellous bone (BCB) as a carrier. NRBX was used alone, in combination with free periosteal graft to repair a 1. 5 cm defect in the radius of rabbit. The defect-repairing capability for each of the treatment modalities was assessed with radiographical, biomechanical, densitometrical and histological methods. Results: NRBX used alone was capable of healing the defect in large by 16 weeks, with a similar repair process and mecha- nism seen with econstituted bone xenograft (RBX). Combined use of NRBX and free periosteal graft was superior in terms of increased and quality of the new bone formed at the early stage of the repair pass (within 12 weeks) to NRBX used alone, with the defect basically healed by 12 weeks. Conclusion: Both methods are effective in repairing segmental bone defects, but NRBX used in combination with free periosteal graft is preferred, because of the satisfactory osteogenesis, osteoconduction and osteoinduction.展开更多
基金Research Fund for the Doctoral Program of Higher Education of China, No. 20060392003
文摘Rat bone marrow mesenchymal stem cells expressing brain-derived neurotrophic factor were successfully obtained using a gene transfection method, then intravenously transplanted into rats with spinal cord injury. At 1,3, and 5 weeks after transplantation, the expression of brain-derived neurotrophic factor and neurofilament-200 was upregulated in the injured spinal cord, spinal cord injury was alleviated, and Basso-Beattie-Bresnahan scores of hindlimb motor function were significantly increased. This evidence suggested that intravenous transplantation of adenovirus- mediated brain-derived neurotrophic factor gene-modified rat bone marrow mesenchymal stem cells could play a dual role, simultaneously providing neural stem cells and neurotrophic factors.
文摘We have shown previously that high-efficient gene transfer can be attained in primary hematopoietic cells using liposome-mediated gene transfer strategy. In order to examine the stability of gene expression mediated by this gene transduction protocol, we observed the expression of marker gene in vivo by using bone marrow transplantation (BMT) to engraft lethally irradiated mouse with the genetically modified hematopoietic cells. The results showed that the mouse transplanted with appropriated number of transduced cells remained alive andhealthy. The PCR analysis and G418 selection of the spleen colonies and bone marrow cells isolated from lethally irradiated animals 15 days and 30 days after injection of genetically modified bone marrow cells showed that the progeny cells of the transduced hematopoietic stem cells still contained and expressed the transduced genes, suggesting that the hematopoietic system is at least partially re-constructed by the stem cells with marker gene and that the stable expression of foreign genes in vivo can be attained by using this easy and harmless transduction protocol. These findings provide experimental basis for clinician to further investigate the biology of marrow reconstruction and the mechanism of leukemia relapse after BMT.
基金supported by grants from the Ministryof Health of China, No. 2011010009the Science and Technology Department of Henan Province, No.112102310230
文摘Previous studies showed that tyrosine hydroxylase or neurturin gene-modified cells transplanted into rats with Parkinson＇s disease significantly improved behavior and increased striatal dopamine content. In the present study, we transplanted tyrosine hydroxylase and neurturin gene-modified bone marrow-derived mesenchymal stem cells into the damaged striatum of Parkinson＇s disease model rats. Several weeks after cell transplantation, in addition to an improvement of motor function tyrosine hydroxylase and neurturin proteins were up-regulated in the injured striatum, and importantly, levels of dopamine and its metabolite 3,4-dihydroxyphenylacetic acid increased significantly. Furthermore, the density of the D2 dopamine receptor in the postsynaptic membranes of dopaminergic neurons was decreased. These results indicate that transplantation of tyrosine hydroxylase and neurturin gene-modified bone marrow-derived mesenchymal stem cells increases dopamine synthesis and significantly improves the behavior of rats with Parkinson＇s disease.
基金supported by a grant from "135 Project" Foundation of the Public Health Department of Jiangsu Province,ChinaNanjing Medical Science and Technique Development Foundation
文摘Adult, male, Sprague-Dawley rats were injected with granulocyte-macrophage colony-stimulating factor-transfected bone marrow stromal cells （GM-CSF-BMSCs） into the ischemic boundary zone at 24 hours after onset of middle cerebral artery occlusion. Results showed reduced infarct volume, decreased number of apoptotic cells, improved neurological functions, increased angiogenic factor expression, and increased vascular density in the ischemic boundary zone in rats that underwent GM-CSF-BMSCs transplantation compared with the BMSCs group. Experimental findings suggested that GM-CSF-BMSCs could serve as a potential therapeutic strategy for ischemic stroke and are superior to BMSCs alone.
基金The Study of Differentiation of Bone Mesenchymal Stem Cells Transplanted in Intervertebral Disc and Expression of ExogenousGene(30400163)
文摘Objective： To explore the survival and migration of bone mesenchymal stem cells transplantated in intervertebral disc of rabbits and expression of the exogenic genes. Methods. Thirty-two rabbits were used, A randomized block design was used and discs in the same rabbit were one block,the lumbar discs from L2-3 to L5-6 were randomly divided into blank group, saline group, cell transplantation group Ⅰand cell transplantation group Ⅱ. The fluorescence microscopy was used to determine the fluorescence of the maker protein GFP and DNA-PCR was used to analyze the copies of DNA of neomycin-resistant gene at 1, 3, 6, months after transplantation. Results： There was fluorescence in cell transplantation group Ⅰ and Ⅱ and none in blank group, saline group at 1, 3, 6 months after transplantation. In cell transplantation groups,the fluorescent distribution was more scatter with time, but no significant difference between cell groups Ⅰ and Ⅱ. The test of neomycin resistant gene expressed in cell transplantation group Ⅰ and Ⅱ and quantitative analysis showed that there was no significant difference between the cell groups Ⅰ and Ⅱ （P〉0.05）. Conclusion： The transplanted bone mesenchymal stem cells can survive, migrate and the transfer genes can express efficiently, it suggests that the BMSC therapy may be effective to prevent and treat intervertebral disc degeneration.
文摘Objective: To study the efficacy of combined use of a new grafting material, new reconstituted bone xenograft (NRBX) and free periosteal graft in repair of segmental bony defects. Methods: NRBX was made by combining recombi- nant human BMP2(rhBMP2) and an antigen-free bovine cancellous bone (BCB) as a carrier. NRBX was used alone, in combination with free periosteal graft to repair a 1. 5 cm defect in the radius of rabbit. The defect-repairing capability for each of the treatment modalities was assessed with radiographical, biomechanical, densitometrical and histological methods. Results: NRBX used alone was capable of healing the defect in large by 16 weeks, with a similar repair process and mecha- nism seen with econstituted bone xenograft (RBX). Combined use of NRBX and free periosteal graft was superior in terms of increased and quality of the new bone formed at the early stage of the repair pass (within 12 weeks) to NRBX used alone, with the defect basically healed by 12 weeks. Conclusion: Both methods are effective in repairing segmental bone defects, but NRBX used in combination with free periosteal graft is preferred, because of the satisfactory osteogenesis, osteoconduction and osteoinduction.
