"VSports注册入口" Allogeneic transplantation of iPS cell-derived cardiomyocytes regenerates primate hearts
- PMID: 27723741
- DOI: 10.1038/nature19815
"V体育安卓版" Allogeneic transplantation of iPS cell-derived cardiomyocytes regenerates primate hearts
Abstract
Induced pluripotent stem cells (iPSCs) constitute a potential source of autologous patient-specific cardiomyocytes for cardiac repair, providing a major benefit over other sources of cells in terms of immune rejection VSports手机版. However, autologous transplantation has substantial challenges related to manufacturing and regulation. Although major histocompatibility complex (MHC)-matched allogeneic transplantation is a promising alternative strategy, few immunological studies have been carried out with iPSCs. Here we describe an allogeneic transplantation model established using the cynomolgus monkey (Macaca fascicularis), the MHC structure of which is identical to that of humans. Fibroblast-derived iPSCs were generated from a MHC haplotype (HT4) homozygous animal and subsequently differentiated into cardiomyocytes (iPSC-CMs). Five HT4 heterozygous monkeys were subjected to myocardial infarction followed by direct intra-myocardial injection of iPSC-CMs. The grafted cardiomyocytes survived for 12 weeks with no evidence of immune rejection in monkeys treated with clinically relevant doses of methylprednisolone and tacrolimus, and showed electrical coupling with host cardiomyocytes as assessed by use of the fluorescent calcium indicator G-CaMP7. 09. Additionally, transplantation of the iPSC-CMs improved cardiac contractile function at 4 and 12 weeks after transplantation; however, the incidence of ventricular tachycardia was transiently, but significantly, increased when compared to vehicle-treated controls. Collectively, our data demonstrate that allogeneic iPSC-CM transplantation is sufficient to regenerate the infarcted non-human primate heart; however, further research to control post-transplant arrhythmias is necessary. .
Comment in
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Induced pluripotent stem cells, form in vitro tissue engineering to in vivo allogeneic transplantation.J Thorac Dis. 2017 Mar;9(3):455-459. doi: 10.21037/jtd.2017.02.77. J Thorac Dis. 2017. PMID: 28449443 Free PMC article. No abstract available.
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Cardiac regeneration using HLA-matched induced pluripotent stem cells-no monkey business, but still a long and winding road ahead.J Thorac Dis. 2017 Mar;9(3):492-494. doi: 10.21037/jtd.2017.03.06. J Thorac Dis. 2017. PMID: 28449453 Free PMC article. No abstract available.
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