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Journal Articles Human gene therapy. Clinical development Year : 2015

Use of Adeno-Associated Virus to Enrich Cardiomyocytes Derived from Human Stem Cells

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Abstract

Cardiomyocytes derived from human induced pluripotent stem cells (iPSCs) show great promise as autologous donor cells to treat heart disease. A major technical obstacle to this approach is that available induction methods often produce heterogeneous cell population with low percentage of cardiomyocytes. Here we describe a cardiac enrichment approach using nonintegrating adeno-associated virus (AAV). We first examined several AAV serotypes for their ability to selectively transduce iPSC-derived cardiomyocytes. Results showed that AAV1 demonstrated the highest in vitro transduction efficiency among seven widely used serotypes. Next, differentiated iPSC derivatives were transduced with drug-selectable AAV1 expressing neomycin resistance gene. Selection with G418 enriched the cardiac cell fraction from 27% to 57% in 2 weeks. Compared with other enrichment strategies such as integrative genetic selection, mitochondria labeling, or surface marker cell sorting, this simple AAV method described herein bypasses antibody or dye labeling. These findings provide proof of concept for large-scale cardiomyocyte enrichment by exploiting AAV’s intrinsic tissue tropism

Dates and versions

inserm-01799977 , version 1 (25-05-2018)

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Xuan Guan, Zejing Wang, Stefan Czerniecki, David Mack, Virginie François, et al.. Use of Adeno-Associated Virus to Enrich Cardiomyocytes Derived from Human Stem Cells. Human gene therapy. Clinical development, 2015, 26 (3), pp.194 - 201. ⟨10.1089/humc.2015.052⟩. ⟨inserm-01799977⟩
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