Cheng Shangli, Brenière-Letuffe David, Ahola Virpi, Wong Andy O T, Keung Hoi Yee, Gurung Bimal, Zheng Zongli, Costa Kevin D, Lieu Deborah K, Keung Wendy, Li Ronald A
Ming Wai Lau Centre for Reparative Medicine, Karolinska Institutet, Hong Kong SAR, China.
Department of Clinical Sciences, Intervention and Technology, CLINTEC, Karolinska Institutet, 141 52 Stockholm, Sweden.
iScience. 2023 Mar 1;26(4):106302. doi: 10.1016/j.isci.2023.106302. eCollection 2023 Apr 21.
Cardiac models have become increasingly obtainable and affordable with the optimization of human pluripotent stem cell-derived cardiomyocyte (hPSC-CM) differentiation. However, these CMs are immature compared to their counterparts. Here we study the cellular phenotype of hPSC-CMs by comparing their single-cell gene expression and functional profiles in three engineered cardiac tissue configurations: human ventricular (hv) cardiac anisotropic sheet, cardiac tissue strip, and cardiac organoid chamber (hvCOC), with spontaneously aggregated 3D cardiac spheroids (CS) as control. The CM maturity was found to increase with increasing levels of complexity of the engineered tissues from CS to hvCOC. The contractile components are the first function to mature, followed by electrophysiology and oxidative metabolism. Notably, the 2D tissue constructs show a higher cellular organization whereas metabolic maturity preferentially increases in the 3D constructs. We conclude that the tissue engineering models resembling configurations of native tissues may be reliable for drug screening or disease modeling.
随着人类多能干细胞衍生心肌细胞（hPSC-CM）分化的优化，心脏模型越来越容易获得且成本更低。然而，与成熟心肌细胞相比，这些心肌细胞并不成熟。在这里，我们通过比较三种工程化心脏组织构型（人心室（hv）心脏各向异性薄片、心脏组织条和心脏类器官腔室（hvCOC））中的单细胞基因表达和功能概况，研究hPSC-CM的细胞表型，并以自发聚集的三维心脏球体（CS）作为对照。研究发现，随着工程化组织从CS到hvCOC的复杂性水平增加，CM成熟度也随之增加。收缩成分是第一个成熟的功能，其次是电生理学和氧化代谢。值得注意的是，二维组织构建体显示出更高的细胞组织性，而代谢成熟度在三维构建体中优先增加。我们得出结论，类似于天然组织构型的组织工程模型可能对药物筛选或疾病建模是可靠的。
