Cell‐to‐cell cross‐talk between mesenchymal stem cells and cardiomyocytes in co‐culture

Abstract

The goals of the study were: (1) to explore the communication between human mesenchymal stem cells (MSC) and rat cardiac myocytes resulting in differentiation of the stem cells and, (2) to evaluate the role of mitochondria in it. Light and fluorescence microscopy as well as scanning electron microscopy revealed that after co-cultivation, cells formed intercellular contacts and transient exchange with cytosolic elements could be observed. The transport of cytosolic entity had no specific direction. Noticeably, mitochondria also could be transferred to the recipient cells in a unidirectional fashion (towards cardiomyocytes only). Transmission electron microscopy revealed significant variability in both the diameter of intercellular contacting tubes and their shape. Inside of these nanotubes mitochondria-resembling structures were identified. Moreover, after co-cultivation with cardiomyocytes, expression of human-specific myosin was revealed in MSC. Thus, we speculate that: (1) transport of intracellular elements to MSC possibly can determine the direction of their differentiation and, (2) mitochondria may be involved in the mechanism of the stem cell differentiation. It looks plausible that mitochondrial transfer to recipient cardiomyocytes may be involved in the mechanism of failed myocardium repair after stem cells transplantation.

Improving the Post-Stroke Therapeutic Potency of Mesenchymal Multipotent Stromal Cells by Cocultivation With Cortical Neurons: The Role of Crosstalk Between Cells

“…Alternatively, we showed that the transport of mitochondria was from MMSCs to neurons or glial cells. Such mitochondrial transfer between MMSCs and cardiomyocytes or renal epithelial cells was previously reported by us [14,16], and others [15,48,49]. Moreover, it has been shown that such a mitochondria "donation" can result in recovery of lost mitochondrial functions in recipient cells [50].…”

“…Because we previously demonstrated that cocultivation of MMSCs with cardiac cells or epitheliocytes associates with proper differentiation [14,16], we explored the possibility of directed differentiation of MMSCs toward neurons or astrocytes after cocultivation. However, after 24 hours of cocultivation of MMSCs with neural culture, we could not detect the expression of neurospecific b-III-tubulin (supplemental online Fig.…”

“…This suggests the existence of some paracrine mechanisms resulting from cell-to-cell interactions. Recently, the possibility of cell-to-cell crosstalk with transfer of cytoplasm [12][13][14] or mitochondria [14][15][16][17] was demonstrated for different types of stem and differentiated cells. For neurons and MMSCs, such interactions have been poorly explored, although the cell-to-cell transfer of cell contents could have a critical role for the physiology of both neurons and MMSCs.…”

Transcriptional Profiling Reveals Crosstalk Between Mesenchymal Stem Cells and Endothelial Cells Promoting Prevascularization by Reciprocal Mechanisms

“…In previous works studying the direct contact interaction between heterogonous cell types, cell types after coculture were sorted by either labeling cell types with cell tracker dyes [49,50] or using specific surface antigens [13]. Our preliminary test indicates that these separation methods might yield a small false positive or false negative rate in the separated cell populations, and in the downstream, might affect the mRNA profiling such as secreting factors and differentiation markers, in which the expression levels might be highly varied.…”

Membrane nanotubes: Novel communication between distant cells

“…Besides electrical signals, bacteria, HIV and quantum dot can be transported by MNTs between mesenchymal stem/stromal cells (MSCs) or immune cells [10,16,24,25], and in our study, mitochondria and intercellular vesicles could be transported via MNTs between CMs and FBs ( Figure 5) [5]. ATP and motor protein kinesin and dynein are required for the cargo transfer [10,26,27].…”