TY - JOUR
T1 - The effect of cyclic stretch on maturation and 3D tissue formation of human embryonic stem cell-derived cardiomyocytes
AU - Mihic, Anton
AU - Li, Jiao
AU - Miyagi, Yasuo
AU - Gagliardi, Mark
AU - Li, Shu Hong
AU - Zu, Jean
AU - Weisel, Richard D.
AU - Keller, Gordon
AU - Li, Ren Ke
PY - 2014/3
Y1 - 2014/3
N2 - The goal of cardiac tissue engineering is to restore function to the damaged myocardium with regenerative constructs. Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) can produce viable, contractile, three-dimensional grafts that function invivo. We sought to enhance the viability and functional maturation of cardiac tissue constructs by cyclical stretch. hESC-CMs seeded onto gelatin-based scaffolds underwent cyclical stretching. Histological analysis demonstrated a greater proportion of cardiac troponin T-expressing cells in stretched than non-stretched constructs, and flow sorting demonstrated a higher proportion of cardiomyocytes. Ultrastructural assessment showed that cells in stretched constructs had a more mature phenotype, characterized by greater cell elongation, increased gap junction expression, and better contractile elements. Real-time PCR revealed enhanced mRNA expression of genes associated with cardiac maturation as well as genes encoding cardiac ion channels. Calcium imaging confirmed that stretched constructs contracted more frequently, with shorter calcium cycle duration. Epicardial implantation of constructs onto ischemic rat hearts demonstrated the feasibility of this platform, with enhanced survival and engraftment of transplanted cells in the stretched constructs. This uniaxial stretching system may serve as a platform for the production of cardiac tissue-engineered constructs for translational applications.
AB - The goal of cardiac tissue engineering is to restore function to the damaged myocardium with regenerative constructs. Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) can produce viable, contractile, three-dimensional grafts that function invivo. We sought to enhance the viability and functional maturation of cardiac tissue constructs by cyclical stretch. hESC-CMs seeded onto gelatin-based scaffolds underwent cyclical stretching. Histological analysis demonstrated a greater proportion of cardiac troponin T-expressing cells in stretched than non-stretched constructs, and flow sorting demonstrated a higher proportion of cardiomyocytes. Ultrastructural assessment showed that cells in stretched constructs had a more mature phenotype, characterized by greater cell elongation, increased gap junction expression, and better contractile elements. Real-time PCR revealed enhanced mRNA expression of genes associated with cardiac maturation as well as genes encoding cardiac ion channels. Calcium imaging confirmed that stretched constructs contracted more frequently, with shorter calcium cycle duration. Epicardial implantation of constructs onto ischemic rat hearts demonstrated the feasibility of this platform, with enhanced survival and engraftment of transplanted cells in the stretched constructs. This uniaxial stretching system may serve as a platform for the production of cardiac tissue-engineered constructs for translational applications.
KW - Cardiac tissue engineering
KW - Cardiomyocyte
KW - Human embryonic stem cell
KW - Scaffold
KW - Transplantation
KW - Uniaxial stretch
UR - http://www.scopus.com/inward/record.url?scp=84895041557&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84895041557&partnerID=8YFLogxK
U2 - 10.1016/j.biomaterials.2013.12.052
DO - 10.1016/j.biomaterials.2013.12.052
M3 - Article
C2 - 24424206
AN - SCOPUS:84895041557
SN - 0142-9612
VL - 35
SP - 2798
EP - 2808
JO - Biomaterials
JF - Biomaterials
IS - 9
ER -