Jackson Ampadu O, Tang Huifang, Yin Kai
Department of Cardiology, The First Affiliated Hospital of University of South China, Hengyang, Hunan Province, China.
Research Lab of Translational Medicine, Hengyang Medical School, University of South China, Hengyang, 421001, China.
J Cardiovasc Transl Res. 2020 Feb;13(1):110-119. doi: 10.1007/s12265-019-09891-4. Epub 2019 May 31.
Despite primary percutaneous coronary intervention (PPCI) and the availability of optimal medications, including dual antiplatelet therapy (DAPT), most patients still experience major adverse cardiovascular events (MACEs) due to frequent recurrence of thrombotic complications and myocardial infarction (MI). MI occurs secondary to a massive loss of endothelial cells (ECs), vascular smooth muscle cells (VSMCs), and cardiomyocytes (CMs). The adult cardiovascular system gradually loses the ability to spontaneously and regularly regenerate ECs, VSMCs, and CMs. However, human cells can be induced by cytokines and growth factors to regenerate human-induced pluripotent stem cells (hiPSCs), which progress to produce cardiac trilineage cells (CTCs) such as ECs, VSMCs, and CMs, replacing lost cells and inducing myocardial repair. Nevertheless, the processes and pathways involved in hiPSC-CTC generation and their potential therapeutic effects remain unknown. Herein, we provide evidence of in vitro CTC generation, the pathways involved, in vivo transplantation, and its therapeutic effect, which may provide novel targets in regenerative medicine for the treatment of cardiovascular diseases (CVDs).
尽管有了直接经皮冠状动脉介入治疗（PPCI）以及包括双联抗血小板治疗（DAPT）在内的最佳药物，但由于血栓形成并发症和心肌梗死（MI）频繁复发，大多数患者仍会发生主要不良心血管事件（MACE）。MI继发于内皮细胞（EC）、血管平滑肌细胞（VSMC）和心肌细胞（CM）的大量损失。成人心血管系统逐渐丧失自发且有规律地再生EC、VSMC和CM的能力。然而，细胞因子和生长因子可诱导人类细胞再生人诱导多能干细胞（hiPSC），后者进而产生心脏三谱系细胞（CTC），如EC、VSMC和CM，替代丢失的细胞并诱导心肌修复。尽管如此，hiPSC-CTC生成所涉及的过程和途径及其潜在治疗效果仍不清楚。在此，我们提供了体外CTC生成、所涉及的途径、体内移植及其治疗效果的证据，这可能为再生医学治疗心血管疾病（CVD）提供新的靶点。
