Cselenyák Attila, Pankotai Eszter, Horváth Eszter M, Kiss Levente, Lacza Zsombor
Institute of Human Physiology and Clinical Experimental Research, Semmelweis University, H-1094, Tuzoltó utca 37-47, Budapest, Hungary.
BMC Cell Biol. 2010 Apr 20;11:29. doi: 10.1186/1471-2121-11-29.
Bone marrow derived mesenchymal stem cells (MSCs) are promising candidates for cell based therapies in myocardial infarction. However, the exact underlying cellular mechanisms are still not fully understood. Our aim was to explore the possible role of direct cell-to-cell interaction between ischemic H9c2 cardiomyoblasts and normal MSCs. Using an in vitro ischemia model of 150 minutes of oxygen glucose deprivation we investigated cell viability and cell interactions with confocal microscopy and flow cytometry.
Our model revealed that adding normal MSCs to the ischemic cell population significantly decreased the ratio of dead H9c2 cells (H9c2 only: 0.85 +/- 0.086 vs. H9c2+MSCs: 0.16 +/- 0.035). This effect was dependent on direct cell-to-cell contact since co-cultivation with MSCs cultured in cell inserts did not exert the same beneficial effect (ratio of dead H9c2 cells: 0.90 +/- 0.055). Confocal microscopy revealed that cardiomyoblasts and MSCs frequently formed 200-500 nm wide intercellular connections and cell fusion rarely occurred between these cells.
Based on these results we hypothesize that mesenchymal stem cells may reduce the number of dead cardiomyoblasts after ischemic damage via direct cell-to-cell interactions and intercellular tubular connections may play an important role in these processes.
骨髓间充质干细胞（MSCs）是心肌梗死细胞治疗中很有前景的候选细胞。然而，确切的潜在细胞机制仍未完全了解。我们的目的是探讨缺血性H9c2心肌母细胞与正常MSCs之间直接细胞间相互作用的可能作用。使用150分钟氧葡萄糖剥夺的体外缺血模型，我们通过共聚焦显微镜和流式细胞术研究了细胞活力和细胞相互作用。
我们的模型显示，向缺血细胞群体中添加正常MSCs可显著降低死亡H9c2细胞的比例（仅H9c2：0.85±0.086 vs. H9c2 + MSCs：0.16±0.035）。这种效应依赖于直接的细胞间接触，因为与培养在细胞插入物中的MSCs共培养没有产生相同的有益效果（死亡H9c2细胞的比例：0.90±0.055）。共聚焦显微镜显示，心肌母细胞和MSCs经常形成200 - 500纳米宽的细胞间连接，并且这些细胞之间很少发生细胞融合。
基于这些结果，我们假设间充质干细胞可能通过直接的细胞间相互作用减少缺血损伤后死亡心肌母细胞的数量，并且细胞间管状连接可能在这些过程中起重要作用。
