1. Human embryonic stem cell-derived cardiovascular progenitor cells efficiently colonize in bFGF-tethered natural matrix to construct contracting humanized rat hearts
- Author
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Hassan Ansari, Sarah Rajabi, Sawa Kostin, Forough Azam Sayahpour, Fahimeh Varzideh, Mohammad Kazemi Ashtiani, Thomas Braun, Saeed Abbasalizadeh, Hossein Baharvand, Sara Pahlavan, and Nasser Aghdami
- Subjects
Male ,0301 basic medicine ,Cellular differentiation ,medicine.medical_treatment ,Human Embryonic Stem Cells ,Basic fibroblast growth factor ,Biophysics ,Bioengineering ,Biology ,Colony-Forming Units Assay ,Biomaterials ,Extracellular matrix ,03 medical and health sciences ,chemistry.chemical_compound ,Tissue engineering ,medicine ,Animals ,Humans ,Cell Lineage ,Myocytes, Cardiac ,Rats, Wistar ,Progenitor cell ,Heart transplantation ,Decellularization ,Tissue Engineering ,Tissue Scaffolds ,Cell Differentiation ,Heart ,Embryonic stem cell ,Extracellular Matrix ,Cell biology ,030104 developmental biology ,Gene Expression Regulation ,chemistry ,Mechanics of Materials ,Ceramics and Composites ,Cattle ,Fibroblast Growth Factor 2 ,Biomedical engineering - 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.
- Published
- 2018