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Adult bone-marrow-derived mesenchymal stem cells contribute to wound healing of skin appendages

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Abstract

Adult bone-marrow-derived mesenchymal stem cells (MSCs) are well-established as having the capacity to differentiate into cells with mesodermal, ectodermal, and endodermal characteristics and can leave their niche to home toward and engraft within foreign tissues. To investigate whether adult MSCs contribute to the repair of skin appendages after injury, BrdU-labeled MSCs were co-cultured with heat-shocked confluent sweat gland cells (SGCs) in vitro and later intravenously injected into full-thickness skin wounds in rats. When adult MSCs were co-cultured with heat-shocked SGCs, a subset of adult MSCs differentiated into SGCs, the percentage of differentiation being enhanced by epidermal growth factor and the injured microenviroment, but weakened by PD98059. The ERK (extracellular signal-regulated kinase) pathway, especially pERK, was involved in the phenotype conversion of human MSCs into human SGC. Labeled MSCs were noted in hair follicles, sebaceous glands, blood vessels, and dermis in full-thickness wounds, and the incorporated cells in hair follicles and sebaceous glands were also positive for pan-cytokeratin. After wound healing, some labeled MSCs returned to the bone marrow, whereas other were retained in the dermis. We conclude that adult MSCs have the capacity to dock at specific sites, to contribute to wound healing of skin appendages, and to home toward marrow, and that engraftment of bone-marrow-derived cells is a functional event.

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References

  • Badiavas EV, Abedi M, Butmarc J, Falanga V, Quesenberry P (2003) Participation of bone marrow derived cells in cutaneous wound healing. J Cell Physiol 196:245–250

    Article  PubMed  CAS  Google Scholar 

  • Ball SG, Shuttleworth AC, Kielty CM (2004) Direct cell contact influences bone marrow mesenchymal stem cell fate. Int J Biochem Cell Biol 36:714–727

    Article  PubMed  CAS  Google Scholar 

  • Blecher SR, Kapalanga J, Lalonde D (1990) Induction of sweat glands by epidermal growth factor in murine X-linked anhidrotic ectodermal dysplasia. Nature 345:542–544

    Article  PubMed  CAS  Google Scholar 

  • Bosnakovski D, Mizuno M, Kim G, Takagi S, Okumura M, Fujinaga T (2005) Isolation and multilineage differentiation of bovine bone marrow mesenchymal stem cells. Cell Tissue Res 319:243–253

    Article  PubMed  Google Scholar 

  • Deng W, Han Q, Liao L, Li C, Ge W, Zhao Z, You S, Deng H, Murad F, Zhao RC (2005) Engrafted bone marrow-derived Flk-1(+) mesenchymal stem cells regenerate skin tissue. Tissue Eng 11:110–119

    Article  PubMed  CAS  Google Scholar 

  • Guerriero R, Parolini I, Testa U, Samoggia P, Petrucci E, Sargiacomo M, Chelucci C, Gabbianelli M, Peschle C (2006) Inhibition of TPO-induced MEK or mTOR activity induces opposite effects on the ploidy of human differentiating megakaryocytes. J Cell Sci 119:744–752

    Article  PubMed  CAS  Google Scholar 

  • Irie HY, Pearline RV, Grueneberg D, Hsia M, Ravichandran P, Kothari N, Natesan S, Brugge JS (2005) Distinct roles of Akt1 and Akt2 in regulating cell migration and epithelial-mesenchymal transition. J Cell Biol 171:1023–1034

    Article  PubMed  CAS  Google Scholar 

  • Jaiswal RK, Jaiswal N, Bruder SP, Mbalaviele G, Marshak DR, Pittenger MF (2000) Adult human mesenchymal stem cell differentiation to the osteogenic or adipogenic lineage is regulated by mitogen-activated protein kinase. J Biol Chem 275:9645–9652

    Article  PubMed  CAS  Google Scholar 

  • Janes SM, Lowell S, Hutter C (2002) Epidermal stem cells. J Pathol 197:479–491

    Article  PubMed  Google Scholar 

  • Jiang Y, Jahagirdar BN, Reinhardt RL, Schwartz RE, Keene CD, Ortiz-Gonzalez XR, Reyes M, Lenvik T, Lund T, Blackstad M, Du J, Aldrich S, Lisberg A, Low WC, Largaespada DA, Verfaillie CM (2002) Pluripotency of mesenchymal stem cells derived from adult marrow. Nature 418:41–49

    Article  PubMed  CAS  Google Scholar 

  • Joannides A, Gaughwin P, Scott M, Watt S, Compston A, Chandran S (2003) Postnatal astrocytes promote neural induction from adult human bone marrow-derived stem cells. J Hematother Stem Cell Res 12:681–688

    Article  PubMed  Google Scholar 

  • Kataoka K, Medina RJ, Kageyama T, Miyazaki M, Yoshino T, Makino T, Huh NH (2003) Participation of adult mouse bone marrow cells in reconstitution of skin. Am J Pathol 163:1227–1231

    PubMed  Google Scholar 

  • Kicic A, Shen WY, Wilson AS, Constable IJ, Robertson T, Rakoczy PE (2003) Differentiation of marrow stromal cells into photoreceptors in the rat eye. J Neurosci 23:7742–7749

    PubMed  CAS  Google Scholar 

  • Krampera M, Pasini A, Rigo A, Scupoli MT, Tecchio C, Malpeli G, Scarpa A, Dazzi F, Pizzolo G, Vinante F (2005) HB-EGF/HER-1 signaling in bone marrow mesenchymal stem cells: inducing cell expansion and reversibly preventing multilineage differentiation. Blood 106:59–66

    Article  PubMed  CAS  Google Scholar 

  • Kulbatski I, Mothe AJ, Nomura H, Tator CH (2005) Endogenous and exogenous CNS derived stem/progenitor cell approaches for neurotrauma.Curr Drug Targets 6:111–126

    Article  PubMed  CAS  Google Scholar 

  • Le Blanc K, Tammik C, Rosendahl K, Zetterberg E, Ringden O (2003) HLA expression and immunologic properties of differentiated and undifferentiated mesenchymal stem cells. Exp Hematol 31:890–896

    Article  PubMed  Google Scholar 

  • Mayhall EA, Paffett-Lugassy N, Zon LI (2004) The clinical potential of stem cells. Curr Opin Cell Biol 16:713–720

    Article  PubMed  CAS  Google Scholar 

  • Oshima Y, Watanabe N, Matsuda K, Takai S, Kawata M, Kubo T (2005) Behavior of transplanted bone marrow-derived GFP mesenchymal cells in osteochondral defect as a simulation of autologous transplantation. J Histochem Cytochem 53:207–216

    Article  PubMed  CAS  Google Scholar 

  • Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284:143–147

    Article  PubMed  CAS  Google Scholar 

  • Rescan C, Le Bras S, Lefebvre VH, Frandsen U, Klein T, Foschi M, Pipeleers DG, Scharfmann R, Madsen OD, Heimberg H (2005) EGF-induced proliferation of adult human pancreatic duct cells is mediated by the MEK/ERK cascade. Lab Invest 85:65–74

    PubMed  CAS  Google Scholar 

  • Safford KM, Rice HE (2005) Stem cell therapy for neurologic disorders: therapeutic potential of adipose-derived stem cells. Curr Drug Targets 6:57–62

    Article  PubMed  CAS  Google Scholar 

  • Saga K (2002) Structure and function of human sweat glands studied with histochemistry and cytochemistry. Prog Histochem Cytochem 37:323–386

    Article  PubMed  CAS  Google Scholar 

  • Schuldiner M, Yanuka O, Itskovitz-Eldor J, Melton DA, Benvenisty N (2000) Effects of eight growth factors on the differentiation of cells derived from human embryonic stem cells. Proc Natl Acad Sci USA 97:11307–11312

    Article  PubMed  CAS  Google Scholar 

  • Shikiji T, Minami M, Inoue T, Hirose K, Oura H, Arase S (2003) Keratinocytes can differentiate into eccrine sweat ducts in vitro: involvement of epidermal growth factor and fetal bovine serum. J Dermatol Sci 33:141–150

    Article  PubMed  CAS  Google Scholar 

  • Silva GV, Litovsky S, Assad JA, Sousa AL, Martin BJ, Vela D, Coulter SC, Lin J, Ober J, Vaughn WK, Branco RV, Oliveira EM, He R, Geng YJ, Willerson JT, Perin EC (2005) Mesenchymal stem cells differentiate into an endothelial phenotype, enhance vascular density, and improve heart function in a canine chronic ischemia model. Circulation 111:150–156

    Article  PubMed  CAS  Google Scholar 

  • Tamama K, Fan VH, Griffith LG, Blair HC, Wells A (2005) Epidermal growth factor as candidate for ex vivo expansion of bone marrow-derived mesenchymal stem cells. Stem Cells 24:686–695

    Article  PubMed  Google Scholar 

  • Tropel P, Noel D, Platet N, Legrand P, Benabid AL, Bergera F (2004) Isolation and characterisation of mesenchymal stem cells from adult mouse bone marrow. Exp Cell Res 295:395–406

    Article  PubMed  CAS  Google Scholar 

  • Wang G, Bunnell BA, Painter RG, Quiniones BC, Tom S, Lanson NA Jr, Spees JL, Bertucci D, Peister A, Weiss DJ, Valentine VG, Prockop DJ, Kolls JK (2005) Adult stem cells from bone marrow stroma differentiate into airway epithelial cells: potential therapy for cystic fibrosis. Proc Natl Acad Sci USA 102:186–191

    Article  PubMed  CAS  Google Scholar 

  • Yang W, Chen Y, Zhang Y, Wang X, Yang N, Zhu D (2006) Extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase pathway is involved in myostatin-regulated differentiation repression. Cancer Res 66:1320–1326

    Article  PubMed  CAS  Google Scholar 

  • Yoon SY, Lee YJ, Seo JH, Sung HJ, Park KH, Choi IK, Kim SJ, Oh SC, Choi CW, Kim BS, Shin SW, Kim YH, Kim JS (2006) uPAR expression under hypoxic conditions depends on iNOS modulated ERK phosphorylation in the MDA-MB-231 breast carcinoma cell line. Cell Res 16:75–81

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Wound Healing and Cell Biology Laboratory, Burns Institute, The First Affiliated Hospital (304th Hospital), General Hospital of PLA, Trauma Center of Postgraduate Medical College, 51 Fu Cheng Road, Beijing, 100037, People’s Republic of China

    Haihong Li, Xiaobing Fu, Yunshu Ouyang, Cunliang Cai, Jun Wang & Tongzhu Sun

  2. Taihe Hospital, Yunyang Medical College, Shiyan, Hubei, 442000, People’s Republic of China

    Haihong Li

Authors
  1. Haihong Li
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  2. Xiaobing Fu
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  3. Yunshu Ouyang
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  4. Cunliang Cai
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  5. Jun Wang
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  6. Tongzhu Sun
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Corresponding author

Correspondence to Xiaobing Fu.

Additional information

This work was supported in part by the National Basic Science and Development Program (973 Program and 2005CB522603) and the National Natural Science Foundation of China (30230370 and 30500194).

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Li, H., Fu, X., Ouyang, Y. et al. Adult bone-marrow-derived mesenchymal stem cells contribute to wound healing of skin appendages. Cell Tissue Res 326, 725–736 (2006). https://doi.org/10.1007/s00441-006-0270-9

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  • DOI: https://doi.org/10.1007/s00441-006-0270-9

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