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Cardiac Cell Cycle Activation as a Strategy to Improve iPSC-Derived Cardiomyocyte Therapy
Circulation Research ( IF 20.1 ) Pub Date : 2018-01-05 , DOI: 10.1161/circresaha.117.312287
June-Wha Rhee 1 , Joseph C. Wu 1
Affiliation  

Over the past 2 decades, scientists and clinicians have strived to leverage stem cell therapy as a treatment for heart failure. However, a myriad of clinical trials investigating the potential of adult stem cells to restore damaged myocardium showed inconsistent effectiveness.1 A subsequent paradigm shift emerged with evidence that the benefits of such treatment, if any, were derived from cardioprotective paracrine factors released by stem cells as opposed to direct myocardial regeneration. As a result, researchers have attempted to regenerate the lost myocardium by delivering cardiac cells to the sites of myocardial damage. Article, see p 88 With recent advances in induced pluripotent stem cell (iPSC) technology, cardiomyocytes can be efficiently and reproducibly generated from iPSCs.2 The use of iPSCs in cell therapy is particularly attractive for the following reasons. First, iPSCs have extensive self-renewal and differentiation potential, which enables generation of a large number of iPSC-derived cardiomyocytes (iPSC-CMs) required for successful cell therapy. Second, this self-renewal property of iPSCs makes them amenable to desired genetic modification before differentiation.3 Third, iPSC-CMs exhibit properties of beating cardiomyocytes and have been shown to engraft in the host myocardium and electromechanically couple to neighboring native cardiomyocytes.4 Finally, because iPSCs are derived from patients’ own somatic cells, the use of autologous iPSC-CMs may help circumvent potential immunogenicity of the transplanted cells.5 Despite these beneficial characteristics of iPSCs, poor survival and engraftment of the transplanted cells remain major obstacles for efficient myocardial regeneration.1 In this issue of Circulation Research , Zhu et al6 sought to test whether the use of genetically engineered, cell cycle–activated iPSC-CMs could improve cardiac cell therapy. Recognizing that only a small fraction of transplanted iPSC-CMs survive and engraft into the myocardium, they hypothesized that if iPSC-CMs could retain proliferative capacity, then even a small …

中文翻译:

心脏细胞周期激活作为改善iPSC衍生心肌细胞治疗的策略

在过去的20年中,科学家和临床医生一直在努力利用干细胞疗法来治疗心力衰竭。但是,大量有关成年干细胞恢复受损心肌的潜力的临床研究表明效果不一致。1随后发生了范式转换,有证据表明这种治疗的益处(如果有的话)源自干细胞释放的心脏保护性旁分泌因子与直接心肌再生相反。结果,研究人员试图通过将心肌细胞传递到心肌损伤部位来再生丢失的心肌。文章,请参阅第88页随着诱导性多能干细胞(iPSC)技术的最新进展,可以从iPSC高效而可再生地产生心肌细胞。2由于以下原因,在细胞疗法中使用iPSC尤其有吸引力。首先,iPSC具有广泛的自我更新和分化潜能,这使得能够产生成功的细胞疗法所需的大量iPSC衍生的心肌细胞(iPSC-CM)。其次,iPSC的这种自我更新特性使其易于在分化之前进行所需的遗传修饰。3第三,iPSC-CM表现出跳动的心肌细胞特性,并已显示其植入宿主心肌并与邻近的天然心肌细胞机电耦合。4最后,因为iPSC来源于患者自身的体细胞,因此使用自体iPSC-CM可能有助于规避移植细胞的潜在免疫原性。5尽管iPSC具有这些有益的特征,存活率低和移植细胞的植入仍然是有效心肌再生的主要障碍。1在本期《循环研究》中,Zhu等人6试图测试使用基因工程,细胞周期激活的iPSC-CM是否可以改善心脏细胞治疗。他们认识到只有一小部分移植的iPSC-CM能够存活并移植到心肌中,因此他们假设,如果iPSC-CM可以保留增生能力,那么即使是……
更新日期:2018-01-05
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