MSCs and Inflammatory Cells Crosstalk in Regenerative Medicine: Concerted Actions for Optimized Resolution Driven by Energy Metabolism

Abstract

Mesenchymal stromal cells (MSCs) are currently widely used in cell based therapy regarding to their remarkable efficacy in controlling the inflammatory status in patients. Despite recent progress and encouraging results, inconstant therapeutic benefits are reported suggesting that significant breakthroughs in the understanding of MSCs immunomodulatory mechanisms of action remains to be investigated and certainly apprehended from original point of view. This review will focus on the recent findings regarding MSCs close relationship with the innate immune compartment, i.e. granulocytes and myeloid cells. The review will also consider the intercellular mechanism of communication involved, such as factor secretion, cell-cell contact, extracellular vesicles, mitochondria transfer and efferocytosis. Immune-like-properties of MSCs supporting part of their therapeutic effect in the clinical setting will be discussed, as well as their potentials (immunomodulatory, anti-bacterial, anti-inflammatory, anti-oxidant defenses and metabolic adaptation…) and effects mediated, such as cell polarization, differentiation, death and survival on various immune and tissue cell targets determinant in triggering tissue regeneration. Their metabolic properties in term of sensing, reacting and producing metabolites influencing tissue inflammation will be highlighted. The review will finally open to discussion how ongoing scientific advances on MSCs could be efficiently translated to clinic in chronic and age-related inflammatory diseases and the current limits and gaps that remain to be overcome to achieving tissue regeneration and rejuvenation.

Treatment of Inflammatory Bowel Disease: A Comprehensive Review

“…MSCs directly target the Th-17 cells and increase their expression of FoxP3 mRNA, thus switching them into Tregs and inhibiting their production of inflammatory cytokines. MSCs can also inhibit the Th1-driven autoimmune response (196)(197)(198). The effect of donor MSCs on the recipient is mainly through paracrine release of various cytokines (199), which not only participate in the regulation of immune response but also promote tissue repair (178).…”

The Implications of Bone Marrow Adipose Tissue on Inflammaging

“…At the cellular level, the BMSC pool in the BM niche shows a biased differentiation towards adipogenesis at the cost of osteoblastogenesis in aging ( 48 ). Despite their regenerative capabilities, BMSCs were shown to have decreased differentiation potential when exposed to inflammatory environments ( 49 ). Josephson et al.…”

In Vitro Characterization of Canine Microfragmented Adipose Tissue Non-Enzymatically Extracted from the Thigh and Lumbar Regions

“…Interleukin-10, also associated with the expression of ASPS, IGF1 and its receptor IRS-1, clearly has chondroprotection activity, stimulating the expression of collagen type II and proteoglycan and regulating the maintenance of tissue integrity [ 48 ]. Moreover, our results demonstrated that adipose tissue also hosts chemokines such as 11β-HSD1, PPARγ, and adiponectin which have been shown to contribute to immunoregulation through modulation of hMSC metabolism [ 49 , 50 ], but also chemokines such as MCP1, Visfatin, and Resistin which have been shown to contribute to immunoregulation through modulation of macrophages plasticity [ 51 ]. Beyond that, adiponectin, ASPS, MCP1, Visfatin, and Resistin, when taken together, prove that they can contribute to the diagnosis of OA, which is consistent with our results.…”