The Role of Extracellular Vesicle and Tunneling Nanotube-Mediated Intercellular Cross-Talk Between Mesenchymal Stem Cells and Human Peripheral T Cells

Abstract

The role of extracellular vesicles (EVs) in mediating the immunosuppressory properties of mesenchymal stem cells (MSCs) has recently attracted remarkable scientific interest. The aim of this work was to analyze the transport mechanisms of membrane and cytoplasmic components between T lymphocytes and adipose tissue-derived MSCs (AD-MSCs), by focusing on the role of distinct populations of EVs, direct cell-cell contacts, and the soluble mediators per se in modulating T lymphocyte function. We found that neither murine thymocytes and human primary T cells nor Jurkat lymphoblastoid cells incorporated appreciable amounts of MSC-derived microvesicles (MVs) or exosomes (EXOs). Moreover, these particles had no effect on the proliferation and IFN-γ production of in vitro-stimulated primary T cells. In contrast, AD-MSCs incorporated large amounts of membrane components from T cells as an intensive uptake of EXOs and MVs could be observed. Interestingly, we found a bidirectional exchange of cytoplasmic components between human AD-MSCs and primary T lymphocytes, mediated by tunneling nanotubes (TNTs) derived exclusively from the T cells. In contrast, TNTs couldn't be observed between AD-MSCs and the Jurkat cells. Our results reveal a novel and efficient way of intercellular communication between MSCs and T cells, and may help a better understanding of the immunomodulatory function of MSCs.

Mesenchymal Stem Cell Administration Attenuates Colon Cancer Progression by Modulating the Immune Component within the Colorectal Tumor Microenvironment

“…TLR4‐primed MSCs secrete proinflammatory mediators while TLR3‐primed MSCs express immunosuppressive effectors. Thus, MSCs can be classified in proinflammatory and immunocompetent MSC1 and immunosuppressive MSC2 . Therefore, the durable antitumor effects of the MSCs observed is most likely explained by “reprogramming” of resident immune cells by the MSCs via epigenetic mechanisms, in agreement with the “hit and run” mechanism suggested by Von Bahr et al .…”

Potential mechanisms of microRNA mobility

“…The latter one describes dynamic, actin‐based cytoplasmic protrusions that connect two cells over long distances of up to several hundred micrometers . Many different cell types were shown to establish TNTs, including stem cells, neural cells, cancer cells and immune cells . The function of TNTs comprise the propagation of calcium flux to regulate cellular physiology, the transmission of antigens in immune cells, and electrical coupling by integration of cx43 proteins .…”

Pathogenic or Therapeutic Extracellular Vesicles in Rheumatic Diseases: Role of Mesenchymal Stem Cell-Derived Vesicles

“…In 2015, Andrade et al showed that MSC-EVs failed to suppress lymphocyte proliferation [67]. Other studies reported that MSC-EVs had no effect on proliferation and IFN-γ production by in vitro-stimulated primary T cells or sorted activated T cells [68,69]. Of interest, opposite effects of MSC-EVs and MSCs were reported.…”