Reciprocal modulation of cell functions upon direct interaction of adipose mesenchymal stromal and activated immune cells

Abstract

The interaction of adipose mesenchymal stromal cells (ASCs) and allogeneic peripheral blood mononuclear cells (PBMCs) is regulated either through direct or paracrine mechanisms. Here, we examined the impact of direct contact in reciprocal regulation of ASC-PBMC functions. Activated PBMCs in vitro induced ASC immunomodulatory activity, while direct and paracrine intercellular interactions regulated PBMCs themselves: the functional state of the organelles was altered, and activation decreased.Direct contact with immune cells affected the activity of ASC intracellular compartments, in particular, reactive oxygen species (ROS) production, and decreased the growth rate. Some ASC properties, including motility, intercellular adhesion molecule-1 (ICAM-1), and major histocompatibility complex class I and II antigens (HLA-ABC and HLA-DR, respectively) expression, did not depend on contact with PBMCs and were only regulated by paracrine means. Direct ASC and PBMC contact favoured an angiogenesis-supportive microenvironment, possibly due to the greater production of VEGF by ASCs; this microenvironment also contained a higher leukemia inhibitory factor (LIF) level. Thus, a change in the functional activity of ASCs and PBMCs upon interaction promoted the formation of an immunosuppressive, anti-inflammatory, and proangiogenic microenvironment. This environment could help resolve inflammation and further restore damaged tissue.Significance of the study: Numerous studies have demonstrated the beneficial effects of transplanted mesenchymal stromal cells, particularly ASCs, for the treatment of a number of autoimmune diseases as well as various tissue injuries. To improve the efficiency of these methods, it is necessary to understand the principal events that occur when ASCs are introduced, primarily the molecular mechanisms of interaction between ASCs and the recipient immune system. We demonstrated that an anti-inflammatory, immunosuppressive, and angiostimulatory shift in the paracrine profile upon the interaction of activated PBMCs and ASCs changes the functional activity of both cell types, a phenomenon that is potentiated by direct cell-cell contact.KEYWORDS allogeneic interaction, direct and paracrine cell-cell interaction, human adipose tissue-derived stromal cells, immunomodulation, peripheral blood mononuclear cells

Adipose derived stem cells (ADSCs) Immunomodulation Impact on Skin Tissue Repair

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“…Using a specific mussel-inspired nanostructure scaffold derived ADSCs to shift macrophages from M1 to M2 immunomodulatory profile, to enhance vascularization thus accelerating wound closure [64]. This result also suggests the crosstalk between ADSCs and local immune cells to address the inflammatory status of their microenvironment which appear to be potentiated by direct cell-cell contact [32,75].…”

Biomaterial-supported MSC transplantation enhances cell–cell communication for spinal cord injury

“…MSCs effectively modulate the immune system and can aid neurological restoration by mediating the immunomodulatory effects via direct cell-cell interactions [64,65]. However, few studies dissect the direct interactions between transplanted cells and immune cells; instead, they measure global changes in cytokine release or the abundance of immune cells after SCI.…”

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“…MSCs effectively modulate the immune system and can aid neurological restoration by mediating their immunomodulatory effects via direct cell-cell interactions [70,71]. However, few studies dissect the direct interactions between transplanted cells and immune cells; instead, they measure global changes in cytokine release or the abundance of immune cells after SCI.…”