Construction of vascularized cardiac tissue from genetically modified mouse embryonic stem cells
| Autor: | Zhaolie Chen, Benchuan Wu, Lingling Ye, Xiao-Bing Fu, Qiwei Wang, Wen-Jun He, Weidong Han, Shichong Li, Hong Liu |
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| Rok vydání: | 2012 |
| Předmět: |
Pulmonary and Respiratory Medicine
Genetically modified mouse Cell Transplantation Cell Culture Techniques Mice Nude Neovascularization Physiologic Biology Transfection Umbilical vein Cell Line Mice In vivo Human Umbilical Vein Endothelial Cells medicine Animals Humans Myocytes Cardiac Embryonic Stem Cells Transplantation Tissue Engineering Cardiac muscle Anatomy Fibroblasts Embryonic stem cell Cell biology Genetically modified organism medicine.anatomical_structure embryonic structures cardiovascular system Feasibility Studies Surgery Genetic Engineering Cardiology and Cardiovascular Medicine |
| Zdroj: | The Journal of Heart and Lung Transplantation. 31:204-212 |
| ISSN: | 1053-2498 |
| Popis: | Background The aim of myocardial tissue engineering is to repair or regenerate damaged myocardium with engineered cardiac tissue constructed by a combination of cells and scaffolds in vitro. However, this strategy has been hampered by the lack of cardiomyocytes and the significant cell death after transplantation in vivo . Methods In this study we explored the feasibility of in vitro construction of vascularized cardiac muscle using genetically modified mouse embryonic stem cells (ESCs) transfected by pMHC-neo/SV40-hygro. A stirred bioreactor was used to facilitate the formation of a large number of ESC-derived cardiomyocytes, which were then mixed with human umbilical vein endothelial cells (HUVECs) and mouse embryonic fibroblasts (MEFs) in a liquid collagen scaffold to construct highly vascularized cardiac tissue in vitro . Results The resulting tissue constructs were transplanted into dorsal subcutaneous sites of nude mice. Tumor formation was not detected in all samples and vascularized cardiac tissue could survive after transplantation. Vascularization of the implanted cardiac muscle was significantly enhanced by the addition of HUVECs and MEFs, which resulted in a thicker myocardium. The combination of genetically modified ESCs and stirred bioreactor cultivation not only benefited the large-scale production of pure ESC-derived cardiomyocytes, but also effectively controlled the potential risk of undifferentiated ESCs. Conclusions Using liquid collagen as scaffold, the enriched cardiomyocytes derived from genetically modified ESCs mixed with HUVECs and MEFs in 3-dimensional culture resulted in highly vascularized cardiac tissues. |
| Databáze: | OpenAIRE |
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