冠状动脉内移植多能干细胞来源的心肌细胞:心脏再生的低效程序。
Intracoronary transplantation of pluripotent stem cell-derived cardiomyocytes: Inefficient procedure for cardiac regeneration.
机构信息
Department of Cardiovascular Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
Department of Cardiology, Keio University School of Medicine, Tokyo, Japan.
出版信息
J Mol Cell Cardiol. 2023 Jan;174:77-87. doi: 10.1016/j.yjmcc.2022.11.004. Epub 2022 Nov 18.
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.
干细胞生物学的进展促进了心脏再生,许多动物研究和几项初步临床试验已经使用人多能干细胞衍生的心肌细胞(PSC-CMs)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-CMs:直接心肌内注射或工程心脏组织的心外膜递送。这两种方法都存在共同的缺点,包括强制性开胸术和较差的植入。此外,尚未建立标准的移植方法。在这项研究中,我们基于常用于移植体干细胞的方法,测试了经冠状动脉给予 PSC-CMs 的可行性。六只雄性食蟹猴接受了分散的人 PSC-CMs 或 PSC-CM 聚集体(称为心脏球体)的经冠状动脉给药,给药剂量不同。移植后 4 周,受体动物被处死进行组织学分析。在食蟹猴中经冠状动脉给予分散的人 PSC-CMs 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,但由于心脏缺血损伤也引起了疤痕形成。心脏植入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,经冠状动脉移植 PSC-CMs 是一种低效的治疗方法。