Department of Medical Life Science, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 137701, Republic of Korea.
Division of Cardiology, Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 137701, Republic of Korea.
Sci Adv. 2020 Mar 25;6(13):eaay6994. doi: 10.1126/sciadv.aay6994. eCollection 2020 Mar.
The clinical use of human bone marrow-derived mesenchymal stem cells (BM-MSCs) has been hampered by their poor performance after transplantation into failing hearts. Here, to improve the therapeutic potential of BM-MSCs, we developed a strategy termed in vivo priming in which BM-MSCs are primed in vivo in myocardial infarction (MI)-induced hearts through genetically engineered hepatocyte growth factor-expressing MSCs (HGF-eMSCs) that are encapsulated within an epicardially implanted 3D cardiac patch. Primed BM-MSCs through HGF-eMSCs exhibited improved vasculogenic potential and cell viability, which ultimately enhanced vascular regeneration and restored cardiac function to the MI hearts. Histological analyses further demonstrated that the primed BM-MSCs survived longer within a cardiac patch and conferred cardioprotection evidenced by substantially higher numbers of viable cardiomyocytes in the MI hearts. These results provide compelling evidence that this in vivo priming strategy can be an effective means to enhance the cardiac repair of MI hearts.
临床应用中，骨髓间充质干细胞（BM-MSCs）移植到衰竭心脏后的疗效并不理想，这一问题限制了其应用。为了提高 BM-MSCs 的治疗潜能，我们开发了一种称为体内预刺激的策略，即将通过基因工程表达肝细胞生长因子的 BM-MSCs（HGF-eMSCs）包裹在心脏外膜贴片中，在心肌梗死（MI）诱导的心脏中进行体内预刺激。通过 HGF-eMSCs 预刺激的 BM-MSCs 表现出改善的血管生成潜能和细胞活力，最终增强了血管再生，并恢复了 MI 心脏的功能。组织学分析进一步表明，预刺激的 BM-MSCs 在心脏贴片内的存活时间更长，并通过 MI 心脏中存活的心肌细胞数量显著增加提供了心脏保护的证据。这些结果提供了有力的证据，证明这种体内预刺激策略可以有效增强 MI 心脏的修复效果。
