Biomedical Science and Engineering Interdisciplinary Program, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea.
Center for Vascular Research, Institute for Basic Science (IBS), Daejeon, Korea.
Sci Rep. 2017 Feb 6;7:41840. doi: 10.1038/srep41840.
Isolating actively proliferating cardioblasts is the first crucial step for cardiac regeneration through cell implantation. However, the origin and identity of putative cardioblasts are still unclear. Here, we uncover a novel class of cardiac lineage cells, PDGFRαFlk1 cardioblasts (PCBs), from mouse and human pluripotent stem cells induced using CsAYTE, a combination of the small molecules Cyclosporin A, the rho-associated coiled-coil kinase inhibitor Y27632, the antioxidant Trolox, and the ALK5 inhibitor EW7197. This novel population of actively proliferating cells is cardiac lineage-committed but in a morphologically and functionally immature state compared to mature cardiomyocytes. Most important, most of CsAYTE-induced PCBs spontaneously differentiated into functional αMHC cardiomyocytes (MCMs) and could be a potential cellular resource for cardiac regeneration.
分离活跃增殖的心肌细胞是通过细胞植入实现心脏再生的第一步。然而，推测的心肌细胞的起源和身份仍不清楚。在这里，我们从使用 CsAYTE（包括环孢素 A、rho 相关卷曲螺旋激酶抑制剂 Y27632、抗氧化剂 Trolox 和 ALK5 抑制剂 EW7197 的小分子组合）诱导的小鼠和人多能干细胞中发现了一类新的心脏谱系细胞，即 PDGFRαFlk1 心肌细胞（PCBs）。这种新型的活跃增殖细胞群是心脏谱系定向的，但与成熟的心肌细胞相比，处于形态和功能不成熟的状态。最重要的是，CsAYTE 诱导的大多数 PCBs 自发分化为功能性 αMHC 心肌细胞（MCMs），并且可能是心脏再生的潜在细胞来源。
