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Cell Journal، جلد ۱۷، شماره Suppl ۱، صفحات ۱۲-۱۳
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عنوان انگلیسی Is-10: In Vitro and In Vivo Models for Cardiac Cell Therapy
چکیده انگلیسی مقاله Objective: Functional integration and persistence of transplanted cardiomyocytes are crucial for a long-term therapeutic benefit of cardiac cell replacement therapy. Induced pluripotent stem cell-derived cardiomyocytes (iPSCM) are regarded as a promising cell type for cardiac cell replacement therapy, but long-term survival and functional integration of these cells have not been demonstrated yet. Thus, we investigated the long-term persistence, electrical integration and electrophysiological properties of transplanted iPSCM. Materials and Methods: For lineage selection within the bioreactor and mass culture as well as to allow the identification of the transplanted cells, transgenic ES and iPS cells were used containing a vector with two cloning sites for EGFP and an puromycin resistance cassette for selection under the α-MHC promoter. We aimed at generating iPSCM and their molecular and functional characterization using genetic, molecular biological and physiological methods. Results: To demonstrate the ability of pluripotent stem cells for regenerative medicine and tissue repair, CMs differentiated from iPS and ES cells were injected into the cryoinfarcted left ventricular wall of adult wild type mice. There is also growing interest in purified cardio-myocytes derived from embryonic stem cells for in vitro or in vivo tissue engineering. We established three-dimensional tissue culture model based cardiac slices, which were seeded either with highly purified cardiomyocytes that have been purified by puromycin selection, alone or in combination with purified fibroblasts. Long-term persistence and electrical integration of transplanted iPSCM into recipient hearts could be clearly demonstrated. Coupling of transplanted iPSCM and host tissue was already observed 6-12 days after transplantation. At later time-points, transplanted iPSCM were still located in recipient hearts and showed electrical coupling to host tissue. The collagen sponges that were transplanted with ES cell derived cardiomyocytes showed neither morphological nor functional integration of the cells. However, when co-cultured with embryonic fibroblasts cardiomyocytes formed fibre-like structures of rod-shaped cells with organized sarcomeric structure. As a consequence the engineered scaffold contracted spontaneously. Electrical coupling between cardiomyocytes was demonstrated by strong expression of connexin 43. Conclusion: We conclude that fibroblasts are needed for morphological and functional engraftment of purified cardiomyocytes on collagen matrices. Translation from the laboratory into the clinic will be one of the future key problems of stem cell research. Although proof of principle for the therapeutic use of iPS cells in cardiac diseases has been shown, both at the laboratory scale and in animal models, the methods used today for generation, cultivation, differentiation and selection are not yet suitable for the clinic.
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نویسندگان مقاله j hescheler | j hescheler


نشانی اینترنتی http://celljournal.org/journal/article/abstract/34
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