Departmental Papers (Dental)
Document Type
Journal Article
Date of this Version
10-2010
Publication Source
Stem Cells
Volume
28
Issue
10
Start Page
1856
Last Page
1868
DOI
10.1002/stem.503
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. © AlphaMed Press.
Keywords
Author keywords: Human gingival, M2 macrophages, Mesenchymal stem cells, Wound healing MeSH: Animals, Blotting, Western, Cell Line, Cells, Cultured, Coculture Techniques, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Gingiva, Humans, Macrophages, Male, Mesenchymal Stem Cells, Mice, Mice, Inbred C57BL, Wound Healing EMTREE drug terms: immunoglobulin enhancer binding protein, interleukin 10, interleukin 6, mannose receptor, tumor necrosis factor alpha EMTREE medical terms: animal experiment, antiinflammatory activity, article, cell expansion, cell infiltration, cell isolation, cell polarity, coculture, controlled study, cytokine production, gingiva derived mesenchymal stem cell, human, human cell, in vivo study, inflammatory cell, macrophage, male, mesenchymal stem cell, mouse, nonhuman, polarization, protein expression, skin injury, Th17 cell, wound healing
Recommended Citation
Zhang, Q., Su, W., Shi, S., Wilder-Smith, P., Xiang, A. P., Wong, A., Nguyen, A. L., Kwon, C. W., & Le, A. D. (2010). Human Gingiva-Derived Mesenchymal Stem Cells Elicit Polarization of M2 Macrophages and Enhance Cutaneous Wound Healing. Stem Cells, 28 (10), 1856-1868. http://dx.doi.org/10.1002/stem.503
Date Posted: 10 February 2023
This document has been peer reviewed.
Comments
At the time of publication, author Qun-Zhou Zhang was affiliated with the Herman Ostrow School of Dentistry, University of Southern California. Currently, (s)he is a faculty member at the School of Dental Medicine at the University of Pennsylvania.
At the time of publication, author Shi-Hong Shi was affiliated with the Herman Ostrow School of Dentistry, University of Southern California. Currently, (s)he is a faculty member at the School of Dental Medicine at the University of Pennsylvania.
At the time of publication, author Chan Wook Kwon was affiliated with the Herman Ostrow School of Dentistry, University of Southern California. Currently, (s)he is a faculty member at the School of Dental Medicine at the University of Pennsylvania.
At the time of publication, author Anh D. Le was affiliated with the Herman Ostrow School of Dentistry, University of Southern California. Currently, (s)he is a faculty member at the School of Dental Medicine at the University of Pennsylvania.