Research ArticleRegenerative Medicine

Transplanted microvessels improve pluripotent stem cell–derived cardiomyocyte engraftment and cardiac function after infarction in rats

See allHide authors and affiliations

Science Translational Medicine  23 Sep 2020:
Vol. 12, Issue 562, eaax2992
DOI: 10.1126/scitranslmed.aax2992

You are currently viewing the abstract.

View Full Text

Log in to view the full text

Log in through your institution

Log in through your institution

Enhancing engraftment

Cell transplant strategies to improve cardiac function after myocardial infarction are plagued by poor engraftment. Sun et al. showed that transplanting microvessels harvested from adipose tissue with cardiomyocytes derived from human induced pluripotent stem cells led to greater cell survival, tissue perfusion, myocyte maturation, and cardiac functional improvements in rats. Cotransplanting microvessels with other cell types could have broad applications for regenerative medicine beyond the cardiovascular system.

Abstract

Human induced pluripotent stem cell–derived cardiomyocytes (hiPSC-CMs) offer an unprecedented opportunity to remuscularize infarcted human hearts. However, studies have shown that most hiPSC-CMs do not survive after transplantation into the ischemic myocardial environment, limiting their regenerative potential and clinical application. We established a method to improve hiPSC-CM survival by cotransplanting ready-made microvessels obtained from adipose tissue. Ready-made microvessels promoted a sixfold increase in hiPSC-CM survival and superior functional recovery when compared to hiPSC-CMs transplanted alone or cotransplanted with a suspension of dissociated endothelial cells in infarcted rat hearts. Microvessels showed unprecedented persistence and integration at both early (~80%, week 1) and late (~60%, week 4) time points, resulting in increased vessel density and graft perfusion, and improved hiPSC-CM maturation. These findings provide an approach to cell-based therapies for myocardial infarction, whereby incorporation of ready-made microvessels can improve functional outcomes in cell replacement therapies.

View Full Text

Stay Connected to Science Translational Medicine