Mesenchymal stem cells rescue cardiomyoblasts from cell death in an in vitro ischemia model via direct cell-to-cell connections

Abstract

Background: 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.Results: 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-tocell 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. Conclusion: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.

How stem cells speak with host immune cells in inflammatory brain diseases

“…Cell-to-cell contacts may also imply the formation of a network of nanotubes between neighboring cells, as described for cardiomyoblasts and MSCs in vitro (Cselenyak et al, 2010).…”

Interaction between Marrow-Derived Human Mesenchymal Stem Cells and Peripheral Blood Mononuclear Cells in Endothelial Cell Differentiation

“…When therapeutically injected, human MSCs have also shown to promote arteriogenesis of ischemic myocardium (11) and the results of most clinical studies are promising (12). A mechanistic explanation for these results might be capacity of MSCs to rescue cardiomyoblasts from cell death, which has recently been demonstrated in an in vitro ischemia model (13).…”

Stem Cell Transplantation in an <em>in vitro</em> Simulated Ischemia/Reperfusion Model

“…Our results showed that added mesenchymal stem cells could improve the survival of postischemic cardiac cells. Confocal microscopy images revealed direct cell-to-cell interactions, such as partial membrane connection or intercellular nanotubes, which probably play an important role in the observed protection 10 . These nanotubes span over distances of several cell diameters, and their diameters were between 200 and 500 nm (white arrows).…”

“…In case of co-cultures, MSCs can be distinguished from H9c2 cells due to their Vybrant DiD cell labeling. The ratio of dead cells can be evaluated in 4 independent fields of view (objective 10x) for each culture in a blind fashion 10 .…”