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Wound healing effect of adipose-derived stem cells: A critical role of secretory factors on human dermal fibroblasts

  • Won-Serk Kim
    Affiliations
    Division of Stem Cell Research, Prostemics Research Institute, Seoul, Republic of Korea

    Department of Dermatology, Kangbuk Samsung Hospital, School of Medicine, Sungkyunkwan University, Seoul, Republic of Korea
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  • Byung-Soon Park
    Correspondence
    Corresponding authors at: Division of Stem Cell Research, Prostemics Research Institute, 60-6, Nonhyun-dong, Kangnam-gu, Seoul 135-010, Republic of Korea. Tel.: +82 2 545 2818; fax: +82 2 545 2819.
    Affiliations
    Division of Stem Cell Research, Prostemics Research Institute, Seoul, Republic of Korea

    Leaders Clinic, Seoul, Republic of Korea
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  • Jong-Hyuk Sung
    Affiliations
    Division of Stem Cell Research, Prostemics Research Institute, Seoul, Republic of Korea
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  • Jun-Mo Yang
    Affiliations
    Department of Dermatology, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul, Republic of Korea
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  • Seok-Beom Park
    Affiliations
    Leaders Clinic, Seoul, Republic of Korea
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  • Sahng-June Kwak
    Affiliations
    Department of Biochemistry, College of Medicine, Dankook University, Chunan, Republic of Korea
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  • Jeong-Soo Park
    Correspondence
    Corresponding authors at: Division of Stem Cell Research, Prostemics Research Institute, 60-6, Nonhyun-dong, Kangnam-gu, Seoul 135-010, Republic of Korea. Tel.: +82 2 545 2818; fax: +82 2 545 2819.
    Affiliations
    Division of Stem Cell Research, Prostemics Research Institute, Seoul, Republic of Korea

    Department of Biochemistry, College of Medicine, Dankook University, Chunan, Republic of Korea
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      Summary

      Background

      Adipose-derived stem cells (ADSCs) are a population of pluripotent cells, which have characteristics similar to bone marrow-derived mesenchymal stem cells. Whereas ADSCs have potential applications for the repair and regeneration of various damaged tissues, few studies have dealt with the effect of ADSCs on fibroblasts, which play a key role in skin biology.

      Objective

      In this study, we investigated the possible roles of ADSCs in skin wound healing process, especially in the aspect of fibroblast activation—proliferation, collagen synthesis and migratory properties.

      Methods and results

      ADSCs promoted human dermal fibroblast (HDF) proliferation, not only by cell-to-cell direct contact, which was confirmed by co-culture experiment, but also by paracrine activation through secretory factors, resolved by transwell co-culture and culturing with conditioned medium of ADSCs (ADSC-CM). ADSC-CM enhanced the secretion of type I collagen in HDFs by regulating the mRNA levels of extracellular matrix (ECM) proteins: up-regulation of collagen type I, III and fibronectin and down-regulation of MMP-1. Moreover, ADSC-CM showed stimulatory effect on migration of HDFs in in vitro wound healing models. Additional to those in vitro evidences, wound healing effect of ADSCs was also verified with in vivo animal study, resulted that ADSCs significantly reduced the wound size and accelerated the re-epithelialization from the edge.

      Conclusion

      Collectively, these data suggest that ADSC is constitutionally well suited for dermal wound healing and secretory factors derived from ADSCs promote wound healing via HDFs and ADSCs can be used for the treatment of photoaging and wound healing.

      Keywords

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      References

        • Zuk P.A.
        • Zhu M.
        • Ashjian P.
        • De Ugarte D.A.
        • Huang J.I.
        • Mizuno H.
        • et al.
        Human adipose tissue is a source of multipotent stem cells.
        Mol Biol Cell. 2002; 13: 4279-4295
        • Zuk P.A.
        • Zhu M.
        • Mizuno H.
        • Huang J.
        • Futrell J.W.
        • Katz A.J.
        • et al.
        Multilineage cells from human adipose tissue: implications for cell-based therapies.
        Tissue Eng. 2001; 7: 211-228
        • Kim C.G.
        • Lee J.J.
        • Jung D.Y.
        • Jeon J.
        • Heo H.S.
        • Kang H.C.
        • et al.
        Profiling of differentially expressed genes in human stem cells by cDNA microarray.
        Mol Cells. 2006; 21: 343-355
        • Katz A.J.
        • Llull R.
        • Hedrick M.H.
        • Futrell J.W.
        Emerging approaches to the tissue engineering of fat.
        Clin Plast Surg. 1999; 26 (viii): 587-603
        • Safford K.M.
        • Hicok K.C.
        • Safford S.D.
        • Halvorsen Y.D.
        • Wilkison W.O.
        • Gimble J.M.
        • et al.
        Neurogenic differentiation of murine and human adipose-derived stromal cells.
        Biochem Biophys Res Commun. 2002; 294: 371-379
        • Barry F.
        • Boynton R.
        • Murphy M.
        • Haynesworth S.
        • Zaia J.
        The SH-3 and SH-4 antibodies recognize distinct epitopes on CD73 from human mesenchymal stem cells.
        Biochem Biophys Res Commun. 2001; 289: 519-524
        • Li H.
        • Fu X.
        • Ouyang Y.
        • Cai C.
        • Wang J.
        • Sun T.
        Adult bone-marrow-derived mesenchymal stem cells contribute to wound healing of skin appendages.
        Cell Tissue Res. 2006; 326: 725-736
        • Puolakkainen P.A.
        • Twardzik D.R.
        • Ranchalis J.E.
        • Pankey S.C.
        • Reed M.J.
        • Gombotz W.R.
        The enhancement in wound healing by transforming growth factor-beta 1 (TGF-beta 1) depends on the topical delivery system.
        J Surg Res. 1995; 58: 321-329
        • Ono I.
        • Gunji H.
        • Zhang J.Z.
        • Maruyama K.
        • Kaneko F.
        Studies on cytokines related to wound healing in donor site wound fluid.
        J Dermatol Sci. 1995; 10: 241-245
        • Le Pillouer-Prost A.
        Fibroblasts: what's new in cellular biology?.
        J Cosmet Laser Ther. 2003; 5: 232-238
        • Gosain A.
        • DiPietro L.A.
        Aging and wound healing.
        World J Surg. 2004; 28: 321-326
        • Park J.S.
        • Park W.Y.
        • Cho K.A.
        • Kim D.I.
        • Jhun B.H.
        • Kim S.R.
        • et al.
        Down-regulation of amphiphysin-1 is responsible for reduced receptor-mediated endocytosis in the senescent cells.
        FASEB J. 2001; 15: 1625-1627
        • Pejnovic N.
        • Lilic D.
        • Zunic G.
        • Colic M.
        • Kataranovski M.
        • Dujic A.
        Aberrant levels of cytokines within the healing wound after burn injury.
        Arch Surg. 1995; 130: 999-1006
        • Mustoe T.A.
        • Pierce G.F.
        • Thomason A.
        • Gramates P.
        • Sporn M.B.
        • Deuel T.F.
        Accelerated healing of incisional wounds in rats induced by transforming growth factor-beta.
        Science. 1987; 237: 1333-1336
        • Broadley K.N.
        • Aquino A.M.
        • Hicks B.
        • Ditesheim J.A.
        • McGee G.S.
        • Demetriou A.A.
        • et al.
        The diabetic rat as an impaired wound healing model: stimulatory effects of transforming growth factor-beta and basic fibroblast growth factor.
        Biotechnol Ther. 1989; 1: 55-68
        • DeLany J.P.
        • Floyd Z.E.
        • Zvonic S.
        • Smith A.
        • Gravois A.
        • Reiners E.
        • et al.
        Proteomic analysis of primary cultures of human adipose-derived stem cells: modulation by Adipogenesis.
        Mol Cell Proteomics. 2005; 4: 731-740
        • Kratchmarova I.
        • Kalume D.E.
        • Blagoev B.
        • Scherer P.E.
        • Podtelejnikov A.V.
        • Molina H.
        • et al.
        A proteomic approach for identification of secreted proteins during the differentiation of 3T3-L1 preadipocytes to adipocytes.
        Mol Cell Proteomics. 2002; 1: 213-222
        • Rehman J.
        • Traktuev D.
        • Li J.
        • Merfeld-Clauss S.
        • Temm-Grove C.J.
        • Bovenkerk J.E.
        • et al.
        Secretion of angiogenic and antiapoptotic factors by human adipose stromal cells.
        Circulation. 2004; 109: 1292-1298
        • Fitzpatrick R.E.
        • Rostan E.F.
        Reversal of photodamage with topical growth factors: a pilot study.
        J Cosmet Laser Ther. 2003; 5: 25-34
        • Inui H.
        • Kitami Y.
        • Kondo T.
        • Inagami T.
        Transduction of mitogenic activity of platelet-derived growth factor (PDGF) AB by PDGF-beta receptor without participation of PDGF-alpha receptor in vascular smooth muscle cells.
        J Biol Chem. 1993; 268: 17045-17050