Human Gingiva-Derived Mesenchymal Stem Cells Elicit Polarization of M2 Macrophages and Enhance Cutaneous Wound Healing  

Abstract

Increasing evidence has supported the important role of mesenchymal stem cells (MSCs) in wound healing, however, the underlying mechanism remains unclear. Recently, we have isolated a unique population of MSCs from human gingiva (GMSCs) with similar stem cell-like properties, immunosuppressive, and anti-inflammatory functions as human bone marrow-derived MSCs (BMSCs). We describe here the interplay between GMSCs and macrophages and the potential relevance in skin wound healing. When cocultured with GMSCs, macrophages acquired an anti-inflammatory M2 phenotype characterized by an increased expression of mannose receptor (MR; CD206) and secretory cytokines interleukin (IL)-10 and IL-6, a suppressed production of tumor necrosis factor (TNF)-α, and decreased ability to induce Th-17 cell expansion. In vivo, we demonstrated that systemically infused GMSCs could home to the wound site in a tight spatial interaction with host macrophages, promoted them toward M2 polarization, and significantly enhanced wound repair. Mechanistically, GMSC treatment mitigated local inflammation mediated by a suppressed infiltration of inflammatory cells and production of IL-6 and TNF-α, and an increased expression of IL-10. The GMSC-induced suppression of TNF-α secretion by macrophages appears to correlate with impaired activation of NFκB p50. These findings provide first evidence that GMSCs are capable to elicit M2 polarization of macrophages, which might contribute to a marked acceleration of wound healing.

Mesenchymal stem cells promote macrophage polarization toward M2b-like cells

“…In agreement with several earlier results [21,49,50], the crosstalk between Ms and MSCs occur primarily by soluble factors, since cytokine production during physical separation of the two cell types was similar to those measured in direct co-cultures. One of the soluble factors produced by both Ms and MSCs is PGE-2.…”

“…Although the interaction between MSCs and T lymphocytes has been extensively studied in the past decades [5], the possible communication between MSCs and MΦs has only been gaining more attention in the last years [20,21]. Former studies mostly focused on the interplay between monocytes or tissue-resident, mainly peritoneal MΦs (Pe-MΦs) and MSCs while the true nature of the effect of MSCs has not been profoundly elucidated on "naïve" (M0) MΦs.…”

Immune Modulation to Improve Tissue Engineering Outcomes for Cartilage Repair in the Osteoarthritic Joint

“…MSC-treated macrophages were reported to express the M2 macrophage marker CD206, with increased expression of IL-10, and low expression of the M1-associated cytokines IL-12 and TNFa. 116,117 Furthermore, transplanted collagen scaffolds seeded with MSCs and polymer complexed-IL-10 plasmids have resulted in macrophage polarization, with an observed increase in CD63…”

Do Mesenchymal Stem Cells Have a Role to Play in Cutaneous Wound Healing?

“…41 MSCs directly interact with macrophages and regulate their phenotype. 42 Furthermore, MSCs produce antimicrobial factors like the LL-37 and promote phagocytosis and bacterial killing possibly through a paracrine mechanism. 43,44 During the wound healing process, MSCs contribute in the reconstitution of local cell population with several ways.…”