Mesenchymal stem cells(MSCs)have been cited as contributors to heart repair through cardiogenic differentiation and multiple cellular interactions,including the paracrine effect,cell fusion,and mechanical and electric...Mesenchymal stem cells(MSCs)have been cited as contributors to heart repair through cardiogenic differentiation and multiple cellular interactions,including the paracrine effect,cell fusion,and mechanical and electrical couplings.Due to heart–muscle complexity,progress in the development of knowledge concerning the role of MSCs in cardiac repair is heavily based on MSC–cardiomyocyte coculture.In conventional coculture systems,however,the in vivo cardiac muscle structure,in which rod-shaped cells are connected end-to-end,is not sustained;instead,irregularly shaped cells spread randomly,resulting in randomly distributed cell junctions.Consequently,contact-mediated cell–cell interactions(e.g.,the electrical triggering signal and the mechanical contraction wave that propagate through MSC–cardiomyocyte junctions)occur randomly.Thus,the data generated on the beneficial effects of MSCs may be irrelevant to in vivo biological processes.In this study,we explored whether cardiomyocyte alignment,the most important phenotype,is relevant to stem cell cardiogenic differentiation.Here,we report(i)the construction of a laser-patterned,biochip-based,stem cell–cardiomyocyte coculture model with controlled cell alignment;and(ii)single-cell-level data on stem cell cardiogenic differentiation under in vivo-like cardiomyocyte alignment conditions.展开更多
基金This work was partially supported by NIH(SC COBRE P20RR021949,Career Award 5k25hl088262-04 and 5R01 HL085847)NSF(MRI,CBET-0923311 and SC EPSCoR RII EPS-0903795 through SC GEAR program)+2 种基金Guangdong Provincial Department of Science and Technology,China(2011B050400011)BZG also acknowledges the support from the grant established by the State Key Laboratory of Precision Measuring Technology and Instruments(Tianjin University)ZM acknowledges his Siebel Institute Postdoctoral Fellowship(41523-31595-44-OYZHMA-IQKEH).
文摘Mesenchymal stem cells(MSCs)have been cited as contributors to heart repair through cardiogenic differentiation and multiple cellular interactions,including the paracrine effect,cell fusion,and mechanical and electrical couplings.Due to heart–muscle complexity,progress in the development of knowledge concerning the role of MSCs in cardiac repair is heavily based on MSC–cardiomyocyte coculture.In conventional coculture systems,however,the in vivo cardiac muscle structure,in which rod-shaped cells are connected end-to-end,is not sustained;instead,irregularly shaped cells spread randomly,resulting in randomly distributed cell junctions.Consequently,contact-mediated cell–cell interactions(e.g.,the electrical triggering signal and the mechanical contraction wave that propagate through MSC–cardiomyocyte junctions)occur randomly.Thus,the data generated on the beneficial effects of MSCs may be irrelevant to in vivo biological processes.In this study,we explored whether cardiomyocyte alignment,the most important phenotype,is relevant to stem cell cardiogenic differentiation.Here,we report(i)the construction of a laser-patterned,biochip-based,stem cell–cardiomyocyte coculture model with controlled cell alignment;and(ii)single-cell-level data on stem cell cardiogenic differentiation under in vivo-like cardiomyocyte alignment conditions.
