Department of Biomedicine & Health Sciences, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 137701, 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, Korea.
Int J Mol Sci. 2021 Feb 1;22(3):1449. doi: 10.3390/ijms22031449.
Human bone marrow-derived mesenchymal stem cells (BM-MSCs), represented as a population of adult stem cells, have long been considered as one of the most promising sources for cell-based cardiac regenerative therapy. However, their clinical use has been significantly hampered by low survival and poor retention following administration into failing hearts. Here, to improve the therapeutic effectiveness of BM-MSCs, we examined a novel therapeutic platform named in situ preconditioning in a rat myocardial infarction (MI) model. In situ preconditioning was induced by a combinatory treatment of BM-MSCs with genetically engineered hepatocyte growth factor-expressing MSCs (HGF-eMSCs) and heart-derived extracellular matrix (hdECM) hydrogel. Subsequently, our results demonstrated that in situ preconditioning with cell mixture substantially improved the survival/retention of BM-MSCs in the MI-induced rat hearts. Enhanced retention of BM-MSCs ultimately led to a significant cardiac function improvement, which was derived from the protection of myocardium and enhancement of vessel formation in the MI hearts. The results provide compelling evidence that in situ preconditioning devised to improve the therapeutic potential of BM-MSCs can be an effective strategy to achieve cardiac repair of MI hearts.
人骨髓间充质干细胞（BM-MSCs）作为一种成体干细胞，长期以来被认为是细胞为基础的心脏再生治疗最有前途的来源之一。然而，它们在用于衰竭心脏后的存活率低和保留率差，极大地限制了其临床应用。在这里，为了提高 BM-MSCs 的治疗效果，我们在大鼠心肌梗死（MI）模型中检查了一种名为原位预处理的新型治疗平台。通过将表达肝细胞生长因子的基因工程间充质干细胞（HGF-eMSCs）和心脏衍生细胞外基质（hdECM）水凝胶与 BM-MSCs 联合处理，诱导原位预处理。随后，我们的结果表明，细胞混合物的原位预处理可显著提高 MI 诱导的大鼠心脏中 BM-MSCs 的存活/保留率。BM-MSCs 的增强保留最终导致心脏功能的显著改善，这源于对 MI 心脏中心肌的保护和血管形成的增强。这些结果提供了有力的证据，表明设计用于提高 BM-MSCs 治疗潜力的原位预处理可以是实现 MI 心脏心脏修复的有效策略。
