Intracoronary transplantation of pluripotent stem cell-derived cardiomyocytes: Inefficient procedure for cardiac regeneration
Intracoronary transplantation of pluripotent stem cell-derived cardiomyocytes: Inefficient procedure for cardiac regeneration
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DOI：
10.1016/j.yjmcc.2022.11.004
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发表时间：
2022-11-29
影响因子：
5
通讯作者：
Fukuda，Keiichi
中科院分区：
文献类型：
--
作者：
Kobayashi，Hideki;Tohyama，Shugo;Fukuda，Keiichi
干细胞生物学的进步促进了心脏再生，许多动物研究和一些初步临床试验已经使用人类多能干细胞衍生的心肌细胞（PSC-CM）进行。大多数临床前和临床研究通常通过以下两种不同的方法移植 PSC-CM：直接心肌内注射或心外膜递送工程心脏组织。这两种方法都有共同的缺点，包括强制开胸和植入不良。此外，标准的移植方法尚未建立。在本研究中，我们测试了基于常用的成体干细胞移植方法进行 PSC-CM 冠状动脉内给药的可行性。六只雄性食蟹猴接受了分散的人类 PSC-CM 或 PSC-CM 聚集体（称为心脏球体）的冠状动脉内注射，具有多种细胞剂量。移植后 4 周处死受体动物进行组织学分析。在食蟹猴中冠状动脉内施用分散的人类 PSC-CM 不会导致冠状动脉栓塞或移植物存活。尽管移植的心脏球体部分植入，但它们也由于心脏缺血性损伤而诱导疤痕形成。心脏移植和疤痕形成与球体大小或细胞剂量相当一致。这些发现表明 PSC-CM 的冠状动脉内移植是一种低效的治疗方法。
Advances in stem cell biology have facilitated cardiac regeneration, and many animal studies and several initial clinical trials have been conducted using human pluripotent stem cell-derived cardiomyocytes (PSC-CMs). Most preclinical and clinical studies have typically transplanted PSC-CMs via the following two distinct approaches: direct intramyocardial injection or epicardial delivery of engineered heart tissue. Both approaches present common disadvantages, including a mandatory thoracotomy and poor engraftment. Furthermore, a standard transplantation approach has yet to be established. In this study, we tested the feasibility of performing intracoronary administration of PSC-CMs based on a commonly used method of transplanting somatic stem cells. Six male cynomolgus monkeys underwent intracoronary administration of dispersed human PSC-CMs or PSC-CM aggregates, which are called cardiac spheroids, with multiple cell dosages. The recipient animals were sacrificed at 4 weeks post-transplantation for histological analysis. Intracoronary administration of dispersed human PSC-CMs in the cynomolgus monkeys did not lead to coronary embolism or graft survival. Although the transplanted cardiac spheroids became partially engrafted, they also induced scar formation due to cardiac ischemic injury. Cardiac engraftment and scar formation were reasonably consistent with the spheroid size or cell dosage. These findings indicate that intracoronary transplantation of PSC-CMs is an inefficient therapeutic approach.