Department of Basic Biomedical Sciences, Dr. William M. Scholl College of Podiatric Medicine, Rosalind Franklin University of Medicine and Science, North Chicago, IL 60064, USA.
Biology Department, Trinity Christian College, Palos Heights, IL 60463, USA.
Int J Mol Sci. 2023 Jun 2;24(11):9653. doi: 10.3390/ijms24119653.
Bone marrow-derived mesenchymal stem cells (BM-MSC) are reported to induce beneficial effects in the heart following ischemia, but a loss of these cells within hours of implantation could significantly diminish their long-term effect. We hypothesized that early coupling between BM-MSC and ischemic cardiomyocytes through gap junctions (GJ) may play an important role in stem cell survival and retention in the acute phase of myocardial ischemia. To determine the effect of GJ inhibition on murine BM-MSC in vivo, we induced ischemia in mice using 90 min left anterior descending coronary artery (LAD) occlusion followed by BM-MSC implantation and reperfusion. The inhibition of GJ coupling prior to BM-MSC implantation led to early improvement in cardiac function compared to mice in which GJ coupling was not inhibited. Our results with in vitro studies also demonstrated increased survival in BM-MSCs subjected to hypoxia after inhibition of GJ. While functional GJ are critical for the long-term integration of stem cells within the myocardium, early GJ communication may represent a novel paradigm whereby ischemic cardiomyocytes induce a "bystander effect" when coupled to newly transplanted BM-MSC and thus impair cell retention and survival.
骨髓间充质干细胞（BM-MSC）被报道在缺血后对心脏有有益的影响，但在植入后数小时内这些细胞的丢失可能会显著降低其长期效果。我们假设，BM-MSC 与缺血性心肌细胞之间通过缝隙连接（GJ）的早期耦联可能在心肌缺血的急性期对干细胞的存活和保留起着重要作用。为了确定 GJ 抑制对体内小鼠 BM-MSC 的影响，我们使用 90 分钟左前降支冠状动脉（LAD）闭塞后再灌注来诱导小鼠缺血，然后植入 BM-MSC。与未抑制 GJ 耦联的小鼠相比，在植入 BM-MSC 之前抑制 GJ 耦联导致早期心功能改善。我们的体外研究结果还表明，抑制 GJ 后，BM-MSC 在缺氧条件下的存活率增加。虽然功能性 GJ 对于干细胞在心肌内的长期整合至关重要，但早期 GJ 通讯可能代表一种新的范例，即当与新移植的 BM-MSC 偶联时，缺血性心肌细胞诱导“旁观者效应”，从而损害细胞的保留和存活。
