Keratinocyte-Like Cells Trans-Differentiated from Human Adipose-Derived Stem Cells, Facilitate Skin Wound Healing in Mice
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Background: Mesenchymal stem cells (MSCs) have been reported to promote wound healing in both animal models and human studies. Among MSCs, adipose-derived stem cells (ADSCs) can be easily harvested in large quantities. Objective: We investigated whether skin wound healing in mice can be facilitated by keratinocyte-like cells differentiated from ADSCs (KC-ADSCs). Methods: For the wound contraction and epithelialization model, a 20 mm×20 mm fullthickness skin wound was made on the dorsum. For the wound epithelialization model, a 6 mm×6 mm full-thickness skin wound was made on the dorsum. A nitrile rubber stent with an inner diameter of 8 mm was sutured around the wounds to minimize wound contraction. Undifferentiated ADSCs (uADSCs) or KC-ADSCs was injected around the wound base in both models. To evaluate whether the injected ADSCs could enhance wound contraction in a skin wound, the contractile activity of ADSCs was assessed by an in vitro type I collagen gel contraction assay. Alpha-smooth muscle actin (αSMA) expressions in uADSCs and KC-ADSCs were also evaluated by flow cytometry and real-time polymerase chain reaction. Results: In a wound contraction and epithelialization model, KC-ADSCs further facilitated wound healing compared with uADSCs. In a wound epithelialization model, KC-ADSCs also further facilitated wound epithelialization compared with uADSCs. The contractile activity of KC-ADSCs was lower than that of uADSCs. The uADSCs expressed high levels of αSMA, which decreased after the differentiation into keratinocyte-like cells. Conclusion: Our results suggest that the wound healing effect of KC-ADSCs depends primarily on re-epithelialization rather than wound contraction. (
Abstract
Background: Mesenchymal stem cells (MSCs) have been reported to promote wound healing in both animal models and human studies. Among MSCs, adipose-derived stem cells (ADSCs) can be easily harvested in large quantities. Objective: We investigated whether skin wound healing in mice can be facilitated by keratinocyte-like cells differentiated from ADSCs (KC-ADSCs). Methods: For the wound contraction and epithelialization model, a 20 mm×20 mm fullthickness skin wound was made on the dorsum. For the wound epithelialization model, a 6 mm×6 mm full-thickness skin wound was made on the dorsum. A nitrile rubber stent with an inner diameter of 8 mm was sutured around the wounds to minimize wound contraction. Undifferentiated ADSCs (uADSCs) or KC-ADSCs was injected around the wound base in both models. To evaluate whether the injected ADSCs could enhance wound contraction in a skin wound, the contractile activity of ADSCs was assessed by an in vitro type I collagen gel contraction assay. Alpha-smooth muscle actin (αSMA) expressions in uADSCs and KC-ADSCs were also evaluated by flow cytometry and real-time polymerase chain reaction. Results: In a wound contraction and epithelialization model, KC-ADSCs further facilitated wound healing compared with uADSCs. In a wound epithelialization model, KC-ADSCs also further facilitated wound epithelialization compared with uADSCs. The contractile activity of KC-ADSCs was lower than that of uADSCs. The uADSCs expressed high levels of αSMA, which decreased after the differentiation into keratinocyte-like cells. Conclusion: Our results suggest that the wound healing effect of KC-ADSCs depends primarily on re-epithelialization rather than wound contraction. (
참고문헌 (39)
- Charbord P, "Bone marrow mesenchymal stem cells : historical overview and concepts", Hum Gene Ther, 21, pp.1045~1056 (2010)
- Sellheyer K, "Skin mesenchymal stem cells : prospects for clinical dermatology", J Am Acad Dermatol, 63, pp.859~865 (2010)
- Shi C, "Stem cells and their applications in skin-cell therapy", Trends Biotechnol, 24, pp.48~52 (2006)
- Fraser JK, "Fat tissue : an underappreciated source of stem cells for biotechnology", Trends Biotechnol, 24, pp.150~154 (2006)
- Zouboulis CC, "Human skin stem cells and the ageing process", Exp Gerontol, 43, pp.986~997 (2008)
- Zuk PA, "Multilineage cells from human adipose tissue : implications for cell-based therapies", Tissue Eng, 7, pp.211~228 (2001)
- Dominici M, "Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement", Cytotherapy, 8, pp.315~317 (2006)
- Barry FP, "Immunogenicity of adult mesenchymal stem cells : lessons from the fetal allograft", Stem Cells Dev, 14, pp.252~265 (2005)
- Caplan AI, "The MSC : an injury drugstore", Cell Stem Cell, 9, pp.11~15 (2011)
- Chen L, "Paracrine factors of mesenchymal stem cells recruit macrophages and endothelial lineage cells and enhance wound healing", PLoS One, 3, pp.e1886~ (2008)
- Wang J, "Mesenchymal-stem-cell-based experimental and clinical trials : current status and open questions", Expert Opin Biol Ther, 11, pp.893~909 (2011)
- Hoogduijn MJ, "Are mesenchymal stromal cells immune cells", Arthritis Res Ther, 17, pp.88~ (2015)
- Bartholomew A, "Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo", Exp Hematol, 30, pp.42~48 (2002)
- McIntosh K, "The immunogenicity of human adiposederived cells : temporal changes in vitro", Stem Cells, 24, pp.1246~1253 (2006)
- Lombardo E, "Toll-like receptor-mediated signaling in human adipose-derived stem cells : implications for immunogenicity and immunosuppressive potential", Tissue Eng Part A, 15, pp.1579~1589 (2009)
- Puissant B, "Immunomodulatory effect of human adipose tissue-derived adult stem cells : comparison with bone marrow mesenchymal stem cells", Br J Haematol, 129, pp.118~129 (2005)
- González MA, "Treatment of experimental arthritis by inducing immune tolerance with human adipose-derived mesenchymal stem cells", Arthritis Rheum, 60, pp.1006~1019 (2009)
- Fang B, "Favorable response to human adipose tissue-derived mesenchymal stem cells in steroid-refractory acute graft-versus-host disease", Transplant Proc, 39, pp.3358~3362 (2007)
- Cho KS, "Immunomodulatory effects of adiposederived stem cells in airway allergic diseases", Curr Stem Cell Res Ther, 5, pp.111~115 (2010)
- Badillo AT, "Treatment of diabetic wounds with fetal murine mesenchymal stromal cells enhances wound closure", Cell Tissue Res, 329, pp.301~311 (2007)
- Li H, "Adult bone-marrow-derived mesenchymal stem cells contribute to wound healing of skin appendages", Cell Tissue Res, 326, pp.725~736 (2006)
- Ma K, "Effects of nanofiber", stem cell composite on wound healing in acute full-thickness skin wounds, 2011, pp.17, 1413~1424
- Schneider RK, "Long-term survival and characterisation of human umbilical cord-derived mesenchymal stem cells on dermal equivalents", Differentiation, 79, pp.182~193 (2010)
- Wu Y, "Mesenchymal stem cells enhance wound healing through differentiation and angiogenesis", Stem Cells, 25, pp.2648~2659 (2007)
- Kwon DS, "Treatment with bone marrow-derived stromal cells accelerates wound healing in diabetic rats", Int Wound J, 5, pp.453~463 (2008)
- Yoshikawa T, "Wound therapy by marrow mesenchymal cell transplantation", Plast Reconstr Surg, 121, pp.860~877 (2008)
- Falanga V, "Autologous bone marrow-derived cultured mesenchymal stem cells delivered in a fibrin spray accelerate healing in murine and human cutaneous wounds", Tissue Eng, 13, pp.1299~1312 (2007)
- Hasegawa T, "Keratinocyte progenitor cells reside in human subcutaneous adipose tissue", PLoS One, 10, pp.e0118402~ (2015)
- Chavez-Munoz C, "Transdifferentiation of adipose-derived stem cells into keratinocyte-like cells : engineering a stratified epidermis", PLoS One, 8, pp.e80587~ (2013)
- Maeda Y, "Adipose-derived stem cells express higher levels of type VII collagen under specific culture conditions", Arch Dermatol Res, 309, pp.843~849 (2017)
- Kilkenny C, "Improving bioscience research reporting : the ARRIVE guidelines for reporting animal research", PLoS Biol, 8, pp.e1000412~ (2010)
- Desmoulière A, "Transforming growth factor-beta 1 induces alpha-smooth muscle actin expression in granulation tissue myofibroblasts and in quiescent and growing cultured fibroblasts", J Cell Biol, 122, pp.103~111 (1993)
- Desmoulière A, "Alpha-smooth muscle actin is expressed in a subpopulation of cultured and cloned fibroblasts and is modulated by gamma-interferon", Exp Cell Res, 201, pp.64~73 (1992)
- Lee YR, "Combination of insulin-like growth factor(IGF)-I and IGF-binding protein-1promotes fibroblast-embedded collagen gel contraction", Endocrinology, 137, pp.5278~5283 (1996)
- Suhr KB, "Sphingosylphosphorylcholine stimulates contraction of fibroblast-embedded collagen gel", Br J Dermatol, 143, pp.66~71 (2000)
- Grinnell F., "Fibroblasts, myofibroblasts, and wound contraction", J Cell Biol, 124, pp.401~404 (1994)
- Nassar D, "Calpain activity is essential in skin wound healing and contributes to scar formation", PLoS One, 7, pp.e37084~ (2012)
- Kopecki Z, "Collagen loss and impaired wound healing is associated with c-Myb deficiency", J Pathol, 211, pp.351~361 (2007)
- Urich K, "Comparative animal biochemistry", pp.376~402 (1994), Springer