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

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 regenerativ...

Full description

Saved in:
Bibliographic Details
Published in:Science translational medicine 2020-09, Vol.12 (562)
Main Authors: Sun, Xuetao, Wu, Jun, Qiang, Beiping, Romagnuolo, Rocco, Gagliardi, Mark, Keller, Gordon, Laflamme, Michael A, Li, Ren-Ke, Nunes, Sara S
Format: Article
Language:English
Subjects:
Adipose tissue
Cardiomyocytes
Endothelial cells
Engraftment
Heart transplantation
Ischemia
Myocardial infarction
Perfusion
Pluripotency
Recovery of function
Stem cells
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1946-6234
1946-6242
1946-3242
DOI:10.1126/scitranslmed.aax2992