Human embryonic stem cell-derived cardiovascular progenitor cells efficiently colonize in bFGF-tethered natural matrix to construct contracting humanized rat hearts.

Abstract:

:Bioengineering of whole hearts using human embryonic stem cells (hESCs)-derived cardiovascular progenitor cells (CPCs) and natural matrices is a promising approach to overcome organ donor shortage threatening millions of patients awaiting for heart transplantation. Here, we developed a novel strategy for generation of heart constructs by repopulating engineered decellularized rat hearts using hESCs-derived CPCs. Careful expansion of CPCs in a scalable stirred-suspension bioreactor combined with step-wise seeding (60 million cells in 3 steps of 20 million per 1.5 h) onto decellularized hearts containing immobilized basic fibroblast growth factor (bFGF) resulted in improved retention of CPCs and differentiation to cardiomyocytes, smooth muscle cells and endothelial cells as evaluated by immunohistochemistry and qRT-PCR. We observed spontaneous and synchronous contractions of humanized hearts after 12 days of perfusion as well as advanced alignment of myofilaments. Our study provides a robust platform for generation of artificial human hearts and resolves major bottlenecks hindering further development of this technology.

journal_name

Biomaterials

journal_title

Biomaterials

authors

Rajabi S,Pahlavan S,Ashtiani MK,Ansari H,Abbasalizadeh S,Sayahpour FA,Varzideh F,Kostin S,Aghdami N,Braun T,Baharvand H

doi

10.1016/j.biomaterials.2017.10.054

subject

Has Abstract

pub_date

2018-02-01 00:00:00

pages

99-112

eissn

0142-9612

issn

1878-5905

pii

S0142-9612(17)30720-2

journal_volume

154

pub_type

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