신지영 (이화여자대학교 약학대학) | 한빛사논문 > 한빛사

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신지영Ji Young Shin

이화여자대학교 약학대학

J. Control. Release, Volume 336, 10 August 2021, Pages 499-509 | https://doi.org/10.1016/j.jconrel.2021.06.040 Intramyocardial delivery of human cardiac stem cell spheroids with enhanced cell engraftment ability and cardiomyogenic potential for myocardial infarct repair

Min Ah Han^a,1, Jeong Hwa Jeon^a,1, Ji Young Shin^a,1, Hee Jung Kim^a, Ji Soo Lee^a, Chae Won Seo^a, Ye Jin Yun^a, Mi Yun Yoon^b, Jong Tae Kim^c, Young Il Yang^c, Seung Jin Lee^a,*

^aDepartment of Pharmacy, Ewha Womans University, 52, Ewhayeodae-gil, Seodaemun-gu, Seoul 03760, Republic of Korea ^bDepartment of Cosmetology, Dongnam Health University, 50, Cheoncheon-ro 74-gil, Jangan-gu, Suwon-si, Gyeonggi-do 16328, Republic of Korea ^cPaik Institute for Clinical Research, Inje University College of Medicine, 75, Bokji-ro, Busanjin-gu, Busan 47392, Republic of Korea

¹These authors contributed equally.

^*Corresponding author.

Abstract

Strategies for stem cell-based cardiac regeneration and repair are key issues for the ischemic heart disease (IHD) patients with chronic complications related to ischemic necrosis. Cardiac stem cells (CSCs) have demonstrated high therapeutic efficacy for IHD treatment owing to their specific cardiac-lineage commitment. The therapeutic potential of CSCs could be further enhanced by designing a cellular spheroid formulation. The spheroid culture condition of CSCs was optimized to ensure regulated size and minimal core necrosis in the spheroids. The CSC spheroids revealed mRNA profiles of the factors related to cardiac regeneration, angiogenesis, anti-inflammatory, and cardiomyocyte differentiation with a higher expression level than the CSCs. Intramyocardially delivered CSC spheroids in the rat IHD model resulted in a significant increase in retention rate by 1.82-fold (day 3) and 1.98-fold (day 14) compared to CSCs. Endothelial cell differentiation and neovascularization of the engrafted CSC spheroids were noted in the infarcted myocardium. CSC spheroids significantly promoted cardiac regeneration: i.e., decreased infarction and fibrotic area (11.22% and 4.18%) and increased left ventricle thickness (0.62 mm) compared to the untreated group. Cardiac performance was also improved by 2.04-fold and 1.44-fold increase in the ejection fraction and fractional shortening, respectively. Intramyocardial administration of CSC spheroids might serve as an advanced therapeutic modality with enhanced cell engraftment and regenerative abilities for cardiac repair after myocardial infarction.

논문정보

형식Research article
게재일2021년 08월 (BRIC 등록일 2021-11-25)
연구진국내 연구진
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