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

Published on Feb 1, 2018in Biomaterials10.27
· DOI :10.1016/j.biomaterials.2017.10.054
Sarah Rajabi3
Estimated H-index: 3
(Royan Institute),
Sara Pahlavan6
Estimated H-index: 6
(Royan Institute)
+ 8 AuthorsHossein Baharvand42
Estimated H-index: 42
(University of Science and Culture)
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.
  • References (51)
  • Citations (4)
#1Samad Ahadian (U of T: University of Toronto)H-Index: 19
#2Locke Davenport Huyer (U of T: University of Toronto)H-Index: 6
Last.Milica Radisic (U of T: University of Toronto)H-Index: 50
view all 8 authors...
#1Doris A. Taylor (The Texas Heart Institute)H-Index: 36
#2Rohan B. Parikh (The Texas Heart Institute)H-Index: 2
Last.Luiz C. Sampaio (The Texas Heart Institute)H-Index: 5
view all 3 authors...
#1Brenda M. Ogle (UMN: University of Minnesota)H-Index: 21
#2Nenad Bursac (Duke University)H-Index: 38
Last.Sean M. Wu (Stanford University)H-Index: 27
view all 10 authors...
Cited By4
#1Dhavan Sharma (MTU: Michigan Technological University)H-Index: 1
#2Morgan Ferguson (MTU: Michigan Technological University)
Last.ZhaoFeng (MTU: Michigan Technological University)H-Index: 23
view all 4 authors...
#1Donald Bejleri (Georgia Institute of Technology)H-Index: 1
#2M. J. Davis (Georgia Institute of Technology)H-Index: 112
Last.Michael Davis (Georgia Institute of Technology)H-Index: 4
view all 3 authors...
#1Kristin M. French (UTSW: University of Texas Southwestern Medical Center)H-Index: 1
#2Michael Davis (Georgia Institute of Technology)H-Index: 4
View next paperCardiac Differentiation of Human Embryonic Stem Cells and their Assembly into Engineered Heart Muscle