Repopulation of decellularized mouse heart with human induced pluripotent stem cell-derived cardiovascular progenitor cells.
Heart disease is the leading cause of death in the world. Heart tissue engineering holds a great promise for future heart disease therapy by building personalized heart tissues. Here we create heart constructs by repopulating decellularized mouse hearts with human induced pluripotent stem cell-derived multipotential cardiovascular progenitor cells. We show that the seeded multipotential cardiovascular progenitor cells migrate, proliferate and differentiate in situ into cardiomyocytes, smooth muscle cells and endothelial cells to reconstruct the decellularized hearts. After 20 days of perfusion, the engineered heart tissues exhibit spontaneous contractions, generate mechanical force and are responsive to drugs. In addition, we observe that heart extracellular matrix promoted cardiomyocyte proliferation, differentiation and myofilament formation from the repopulated human multipotential cardiovascular progenitor cells. Our novel strategy to engineer personalized heart constructs could benefit the study of early heart formation or may find application in preclinical testing.
Department of Developmental Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15201, USA.
Tung-Ying
TY
Lu
Bo
B
Lin
Jong
J
Kim
Mara
M
Sullivan
Kimimasa
K
Tobita
Guy
G
Salama
Lei
L
Yang
D000818:Animals; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology; D048091:Guided Tissue Regeneration / Q000379:methods*; D006321:Heart; D006331:Heart Diseases / Q000628:therapy; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D023822:Tissue Engineering / Q000379:methods*