Probing the subcellular nanostructure of engineered human cardiomyocytes in 3D tissue  

作　　者：Josh Javor Jourdan K.Ewoldt Paige E.Cloonan Anant Chopra Rebeccah J.Luu Guillaume Freychet Mikhail Zhernenkov Karl Ludwig Jonathan G.Seidman Christine E.Seidman Christopher S.Chen David J.Bishop 

机构地区：[1]Department of Mechanical Engineering,Boston University,Boston,MA 02215,USA [2]Department of Biomedical Engineering,Boston University,Boston,MA 02215,USA [3]SMI Beamline 12-ID,Brookhaven National Laboratory,Upton,NY 11973,USA [4]Department of Physics,Boston University,Boston,MA 02215,USA [5]Division of Materials Science,Boston University,Boston,Massachusetts 02215,USA [6]Department of Genetics,Harvard Medical School,Boston,MA 02215,USA [7]Department of Electrical Engineering,Boston University,Boston,MA 02215,USA

出　　处：《Microsystems & Nanoengineering》2021年第1期133-140,共8页微系统与纳米工程（英文）

基　　金：supported by NSF CELL-MET ERC award no.1647837 and NSF GRFP(DGE-1840990,J.K.E.)。

摘　　要：The structural and functional maturation of human induced pluripotent stem cell-derived cardiomyocytes(hiPSC-CMs)is essential for pharmaceutical testing,disease modeling,and ultimately therapeutic use.Multicellular 3D-tissue platforms have improved the functional maturation of hiPSC-CMs,but probing cardiac contractile properties in a 3D environment remains challenging,especially at depth and in live tissues.Using small-angle X-ray scattering(SAXS)imaging,we show that hiPSC-CMs matured and examined in a 3D environment exhibit a periodic spatial arrangement of the myofilament lattice,which has not been previously detected in hiPSC-CMs.The contractile force is found to correlate with both the scattering intensity(R^(2)=0.44)and lattice spacing(R^(2)=0.46).The scattering intensity also correlates with lattice spacing(R^(2)=0.81),suggestive of lower noise in our structural measurement than in the functional measurement.Notably,we observed decreased myofilament ordering in tissues with a myofilament mutation known to lead to hypertrophic cardiomyopathy(HCM).Our results highlight the progress of human cardiac tissue engineering and enable unprecedented study of structural maturation in hiPSC-CMs.

关 键 词：cardiac CARDIOMYOCYTES SPACING 

分 类 号：R542.2[医药卫生—心血管疾病]