Human embryonic stem cell-derived cardiovascular progenitor cells efficiently colonize in bFGF-tethered natural matrix to construct contracting humanized rat hearts.
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.
['Rajabi|Sarah|S|', 'Pahlavan|Sara|S|', 'Ashtiani|Mohammad Kazemi|MK|', 'Ansari|Hassan|H|', 'Abbasalizadeh|Saeed|S|', 'Sayahpour|Forough Azam|FA|', 'Varzideh|Fahimeh|F|', 'Kostin|Sawa|S|', 'Aghdami|Nasser|N|', 'Braun|Thomas|T|', 'Baharvand|Hossein|H|']
D000818:Animals D002417:Cattle D002454:Cell Differentiation D019070:Cell Lineage D003114:Colony-Forming Units Assay D005109:Extracellular Matrix D016222:Fibroblast Growth Factor 2 D005786:Gene Expression Regulation D006321:Heart D000066449:Human Embryonic Stem Cells D006801:Humans D008297:Male D032383:Myocytes, Cardiac D017208:Rats, Wistar D023822:Tissue Engineering D054457:Tissue Scaffolds
Cardiovascular progenitor cell Heart bFGF Organ bioengineering Scalable culture