title: Coupling primary and stem cell-derived cardiomyocytes in an in vitro model of cardiac cell therapy.
abstract: The efficacy of cardiac cell therapy depends on the integration of existing and newly formed cardiomyocytes. Here, we developed a minimal in vitro model of this interface by engineering two cell microtissues (μtissues) containing mouse cardiomyocytes, representing spared myocardium after injury, and cardiomyocytes generated from embryonic and induced pluripotent stem cells, to model newly formed cells. We demonstrated that weaker stem cell-derived myocytes coupled with stronger myocytes to support synchronous contraction, but this arrangement required focal adhesion-like structures near the cell-cell junction that degrade force transmission between cells. Moreover, we developed a computational model of μtissue mechanics to demonstrate that a reduction in isometric tension is sufficient to impair force transmission across the cell-cell boundary. Together, our in vitro and in silico results suggest that mechanotransductive mechanisms may contribute to the modest functional benefits observed in cell-therapy studies by regulating the amount of contractile force effectively transmitted at the junction between newly formed and spared myocytes.
authors: Disease Biophysics Group, Wyss Institute of Biologically Inspired Engineering, John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138.
authors: Yvonne
authors: Y
authors: Aratyn-Schaus
authors: Disease Biophysics Group, Wyss Institute of Biologically Inspired Engineering, John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138.
authors: Francesco S
authors: FS
authors: Pasqualini
authors: Disease Biophysics Group, Wyss Institute of Biologically Inspired Engineering, John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138.
authors: Hongyan
authors: H
authors: Yuan
authors: Disease Biophysics Group, Wyss Institute of Biologically Inspired Engineering, John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138.
authors: Megan L
authors: ML
authors: McCain
authors: Disease Biophysics Group, Wyss Institute of Biologically Inspired Engineering, John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138.
authors: George J C
authors: GJ
authors: Ye
authors: Disease Biophysics Group, Wyss Institute of Biologically Inspired Engineering, John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138.
authors: Sean P
authors: SP
authors: Sheehy
authors: Disease Biophysics Group, Wyss Institute of Biologically Inspired Engineering, John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138.
authors: Patrick H
authors: PH
authors: Campbell
authors: Disease Biophysics Group, Wyss Institute of Biologically Inspired Engineering, John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138 kkparker@seas.harvard.edu.
authors: Kevin Kit
authors: KK
authors: Parker
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism; D002450:Cell Communication; D002454:Cell Differentiation; D002478:Cells, Cultured; D003198:Computer Simulation; D022001:Focal Adhesions / Q000378:metabolism; D040542:Mechanotransduction, Cellular; D051379:Mice; D008807:Mice, Inbred BALB C; D008955:Models, Cardiovascular; D009200:Myocardial Contraction; D032383:Myocytes, Cardiac / Q000502:physiology* / Q000637:transplantation; D010641:Phenotype; D061251:Primary Cell Culture; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000502:physiology*; D013314:Stress, Mechanical; D013997:Time Factors; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D002118:Calcium