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Mesenchymal Cells that Support Human Skin Regeneration

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Regenerative Medicine and Plastic Surgery

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Abstract

Human skin regeneration is highly dependent on the growth factors provided by mesenchymal support cells. Here we review the current understanding of the various cell types both heterotypic and homotypic that are capable of promoting the culture, expansion, and tissue regenerative ability of epidermal cells in both conventional 2D and organotypic 3D experimental model systems. We also review the potential mechanisms by which mesenchymal cells support epidermal cell proliferation and maturation including growth factors and extracellular matrix proteins. The advances made in recent years have been instrumental in beginning to understand the complex microenvironment or niche of epidermal stem and progenitors and how it can be manipulated to design more optimal clinical approaches for the treatment of skin deficits.

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References

  1. Baroni A, Buommino E, De Gregorio V, Ruocco E, Ruocco V, Wolf R. Structure and function of the epidermis related to barrier properties. Clin Dermatol. 2012;30(3):257–62.

    Article  PubMed  Google Scholar 

  2. Ojeh N, Pastar I, Tomic-Canic M, Stojadinovic O. Stem cells in skin regeneration, wound healing, and their clinical applications. Int J Mol Sci. 2015;16(10):25476–501.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Watt FM. Mammalian skin cell biology: at the interface between laboratory and clinic. Science. 2014;346(6212):937–40.

    Article  CAS  PubMed  Google Scholar 

  4. Lawlor KT, Kaur P. Dermal contributions to human interfollicular epidermal architecture and self-renewal. Int J Mol Sci. 2015;16(12):28098–107.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Rowan MP, Cancio LC, Elster EA, Burmeister DM, Rose LF, Natesan S, Chan RK, Christy RJ, Chung KK. Burn wound healing and treatment: review and advancements. Crit Care. 2015;19:243.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Simões MC, Sousa JJ, Pais AA. Skin cancer and new treatment perspectives: a review. Cancer Lett. 2015;357(1):8–42.

    Article  PubMed  CAS  Google Scholar 

  7. Green H. The birth of therapy with cultured cells. BioEssays. 2008;30(9):897–903.

    Article  PubMed  Google Scholar 

  8. Sriram G, Bigliardi PL, Bigliardi-Qi M. Fibroblast heterogeneity and its implications for engineering organotypic skin models in vitro. Eur J Cell Biol. 2015;94(11):483–512.

    Article  CAS  PubMed  Google Scholar 

  9. Fuchs E. Skin stem cells: rising to the surface. J Cell Biol. 2008;180(2):273–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Blanpain C, Fuchs E. Epidermal stem cells of the skin. Annu Rev Cell Dev Biol. 2006;22:339–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Jones PH, Watt FM. Separation of human epidermal stem cells from transit amplifying cells on the basis of differences in integrin function and expression. Cell. 1993;73(4):713–24.

    Article  CAS  PubMed  Google Scholar 

  12. Jones PH, Harper S, Watt FM. Stem cell patterning and fate in human epidermis. Cell. 1995;80(1):83–93.

    Article  CAS  PubMed  Google Scholar 

  13. Jensen UB, Lowell S, Watt FM. The spatial relationship between stem cells and their progeny in the basal layer of human epidermis: a new view based on whole-mount labelling and lineage analysis. Development. 1999;126(11):2409–18.

    Article  CAS  PubMed  Google Scholar 

  14. Legg J, Jensen UB, Broad S, Leigh I, Watt FM. Role of melanoma chondroitin sulphate proteoglycan in patterning stem cells in human interfollicular epidermis. Development. 2003;130(24):6049–63.

    Article  CAS  PubMed  Google Scholar 

  15. Jensen KB, Collins CA, Nascimento E, Tan DW, Frye M, Itami S, Watt FM. Lrig1 expression defines a distinct multipotent stem cell population in mammalian epidermis. Cell Stem Cell. 2009;4(5):427–39.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Li A, Simmons PJ, Kaur P. Identification and isolation of candidate human keratinocyte stem cells based on cell surface phenotype. Proc Natl Acad Sci U S A. 1998;95(7):3902–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Li A, Pouliot N, Redvers R, Kaur P. Extensive tissue-regenerative capacity of neonatal human keratinocyte stem cells and their progeny. J Clin Invest. 2004;113(3):390–400.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Schluter H, Paquet-Fifield S, Gangatirkar P, Li J, Kaur P. Functional characterization of quiescent keratinocyte stem cells and their progeny reveals a hierarchical organization in human skin epidermis. Stem Cells. 2011;29(8):1256–68.

    Article  PubMed  Google Scholar 

  19. Webb A, Li A, Kaur P. Location and phenotype of human adult keratinocyte stem cells of the skin. Differentiation. 2004;72(8):387–95.

    Article  PubMed  Google Scholar 

  20. Lechler T, Fuchs E. Asymmetric cell divisions promote stratification and differentiation of mammalian skin. Nature. 2005;437(7056):275–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Gangatirkar P, Paquet-Fifield S, Li A, Rossi R, Kaur P. Establishment of 3D organotypic cultures using human neonatal epidermal cells. Nat Protoc. 2007;2(1):178–86.

    Article  CAS  PubMed  Google Scholar 

  22. Breitkreutz D, Koxholt I, Thiemann K, Nischt R. Skin basement membrane: the foundation of epidermal integrity—BM functions and diverse roles of bridging molecules nidogen and perlecan. Biomed Res Int. 2013;2013:179784.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Sorrell JM, Caplan AI. Fibroblast heterogeneity: more than skin deep. J Cell Sci. 2004;117(Pt 5):667–75.

    Article  CAS  PubMed  Google Scholar 

  24. Driskell RR, Watt FM. Understanding fibroblast heterogeneity in the skin. Trends Cell Biol. 2015;25(2):92–9.

    Article  CAS  PubMed  Google Scholar 

  25. Braverman IM. The cutaneous microcirculation. J Investig Dermatol Symp Proc. 2000;5(1):3–9.

    Article  CAS  PubMed  Google Scholar 

  26. Birbrair A, Zhang T, Wang Z-M, Messi ML, Mintz A, Delbono O. Pericytes at the intersection between tissue regeneration and pathology. Clin Sci. 2015;128(2):81–93.

    Article  CAS  Google Scholar 

  27. Paquet-Fifield S, Schluter H, Li A, Aitken T, Gangatirkar P, Blashki D, Koelmeyer R, Pouliot N, Palatsides M, Ellis S, Brouard N, Zannettino A, Saunders N, Thompson N, Li J, Kaur P. A role for pericytes as microenvironmental regulators of human skin tissue regeneration. J Clin Invest. 2009;119(9):2795–806.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Gaur M, Dobke M, Lunyak VV. Mesenchymal stem cells from adipose tissue in clinical applications for dermatological indications and skin aging. Int J Mol Sci. 2017;18(1):E208.

    Article  PubMed  CAS  Google Scholar 

  29. Nestle FO, Di Meglio P, Qin J-Z, Nickoloff BJ. Skin immune sentinels in health and disease. Nat Rev Immunol. 2009;9(10):679–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Mann ER, Smith KM, Bernardo D, Al-Hassi HO, Knight SC, Hart HL. Review: skin and the immune system. J Clin Exp Dermatol Res. 2012;S2:003.

    Google Scholar 

  31. Minutti CM, Knipper JA, Allen JE, Zaiss DMW. Tissue-specific contribution of macrophages to wound healing. Semin Cell Dev Biol. 2017;61(Suppl C):3–11.

    Article  CAS  PubMed  Google Scholar 

  32. Rheinwald JG, Green H. Serial cultivation of strains of human epidermal keratinocytes: the formation of keratinizing colonies from single cells. Cell. 1975;6(3):331–43.

    Article  CAS  PubMed  Google Scholar 

  33. Green H, Rheinwald JG, Sun TT. Properties of an epithelial cell type in culture: the epidermal keratinocyte and its dependence on products of the fibroblast. Prog Clin Biol Res. 1977;17:493–500.

    CAS  PubMed  Google Scholar 

  34. Oh JW, Hsi TC, Guerrero-Juarez CF, Ramos R, Plikus MV. Organotypic skin culture. J Invest Dermatol. 2013;133(11):1–4.

    Article  PubMed  CAS  Google Scholar 

  35. Nanba D, Matsushita N, Toki F, Higashiyama S. Efficient expansion of human keratinocyte stem/progenitor cells carrying a transgene with lentiviral vector. Stem Cell Res Ther. 2013;4(5):127.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. Pellegrini G, Ranno R, Stracuzzi G, Bondanza S, Guerra L, Zambruno G, Micali G, De Luca M. The control of epidermal stem cells (holoclones) in the treatment of massive full-thickness burns with autologous keratinocytes cultured on fibrin. Transplantation. 1999;68(6):868–79.

    Article  CAS  PubMed  Google Scholar 

  37. Ronfard V, Rives JM, Neveux Y, Carsin H, Barrandon Y. Long-term regeneration of human epidermis on third degree burns transplanted with autologous cultured epithelium grown on a fibrin matrix. Transplantation. 2000;70(11):1588–98.

    Article  CAS  PubMed  Google Scholar 

  38. Jubin K, Martin Y, Lawrence-Watt DJ, Sharpe JR. A fully autologous co-culture system utilising non-irradiated autologous fibroblasts to support the expansion of human keratinocytes for clinical use. Cytotechnology. 2011;63(6):655–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Higham MC, Dawson R, Szabo M, Short R, Haddow DB, MacNeil S. Development of a stable chemically defined surface for the culture of human keratinocytes under serum-free conditions for clinical use. Tissue Eng. 2003;9(5):919–30.

    Article  CAS  PubMed  Google Scholar 

  40. Sun T, Higham M, Layton C, Haycock J, Short R, MacNeil S. Developments in xenobiotic-free culture of human keratinocytes for clinical use. Wound Repair Regen. 2004;12(6):626–34.

    Article  PubMed  Google Scholar 

  41. Bullock AJ, Higham MC, MacNeil S. Use of human fibroblasts in the development of a xenobiotic-free culture and delivery system for human keratinocytes. Tissue Eng. 2006;12(2):245–55.

    Article  CAS  PubMed  Google Scholar 

  42. Mujaj S, Manton K, Upton Z, Richards S. Serum-free primary human fibroblast and keratinocyte coculture. Tissue Eng Part A. 2010;16(4):1407–20.

    Article  CAS  PubMed  Google Scholar 

  43. El-Ghalbzouri A, Gibbs S, Lamme E, Van Blitterswijk CA, Ponec M. Effect of fibroblasts on epidermal regeneration. Br J Dermatol. 2002;147(2):230–43.

    Article  CAS  PubMed  Google Scholar 

  44. El Ghalbzouri A, Lamme E, Ponec M. Crucial role of fibroblasts in regulating epidermal morphogenesis. Cell Tissue Res. 2002;310(2):189–99.

    Article  PubMed  Google Scholar 

  45. Boehnke K, Mirancea N, Pavesio A, Fusenig NE, Boukamp P, Stark HJ. Effects of fibroblasts and microenvironment on epidermal regeneration and tissue function in long-term skin equivalents. Eur J Cell Biol. 2007;86(11–12):731–46.

    Article  CAS  PubMed  Google Scholar 

  46. Llames S, Garcia E, Garcia V, del Rio M, Larcher F, Jorcano JL, López E, Holguín P, Miralles F, Otero J, Meana A. Clinical results of an autologous engineered skin. Cell Tissue Bank. 2006;7(1):47–53.

    Article  PubMed  Google Scholar 

  47. Llames SG, Del Rio M, Larcher F, Garcia E, Garcia M, Escamez MJ, Jorcano JL, Holguín P, Meana A. Human plasma as a dermal scaffold for the generation of a completely autologous bioengineered skin. Transplantation. 2004;77(3):350–5.

    Article  PubMed  Google Scholar 

  48. Bisson F, Rochefort É, Lavoie A, Larouche D, Zaniolo K, Simard-Bisson C, Damour O, Auger FA, Guérin SL, Germain L. Irradiated human dermal fibroblasts are as efficient as mouse fibroblasts as a feeder layer to improve human epidermal cell culture lifespan. Int J Mol Sci. 2013;14(3):4684–704.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Auxenfans C, Thepot A, Justin V, Hautefeuille A, Shahabeddin L, Damour O, Hainaut P. Characterisation of human fibroblasts as keratinocyte feeder layer using p63 isoforms status. Biomed Mater Eng. 2009;19(4–5):365–72.

    PubMed  Google Scholar 

  50. Panacchia L, Dellambra E, Bondanza S, Paterna P, Maurelli R, Paionni E, Guerra L. Nonirradiated human fibroblasts and irradiated 3T3-J2 murine fibroblasts as a feeder layer for keratinocyte growth and differentiation in vitro on a fibrin substrate. Cells Tissues Organs. 2010;191(1):21–35.

    Article  PubMed  Google Scholar 

  51. Meana A, Iglesias J, Del Rio M, Larcher F, Madrigal B, Fresno MF, Martin C, San Roman F, Tevar F. Large surface of cultured human epithelium obtained on a dermal matrix based on live fibroblast-containing fibrin gels. Burns. 1998;24(7):621–30.

    Article  CAS  PubMed  Google Scholar 

  52. Kamolz LP, Luegmair M, Wick N, Eisenbock B, Burjak S, Koller R, Meissl G, Frey M. The Viennese culture method: cultured human epithelium obtained on a dermal matrix based on fibroblast containing fibrin glue gels. Burns. 2005;31(1):25–9.

    Article  CAS  PubMed  Google Scholar 

  53. Ng W, Ikeda S. Standardized, defined serum-free culture of a human skin equivalent on fibroblast-populated collagen scaffold. Acta Derm Venereol. 2011;91(4):387–91.

    Article  CAS  PubMed  Google Scholar 

  54. Chen C-SJ, Lavker RM, Rodeck U, Risse B, Jensen PJ. Use of a serum-free epidermal culture model to show deleterious effects of epidermal growth factor on morphogenesis and differentiation. J Invest Dermatol. 1995;104(1):107–12.

    Article  CAS  PubMed  Google Scholar 

  55. Sorrell JM, Baber MA, Caplan AI. Site-matched papillary and reticular human dermal fibroblasts differ in their release of specific growth factors/cytokines and in their interaction with keratinocytes. J Cell Physiol. 2004;200(1):134–45.

    Article  CAS  PubMed  Google Scholar 

  56. Varkey M, Ding J, Tredget EE. Fibrotic remodeling of tissue-engineered skin with deep dermal fibroblasts is reduced by keratinocytes. Tissue Eng Part A. 2014;20(3–4):716–27.

    CAS  PubMed  Google Scholar 

  57. Varkey M, Ding J, Tredget EE. Superficial dermal fibroblasts enhance basement membrane and epidermal barrier formation in tissue-engineered skin: implications for treatment of skin basement membrane disorders. Tissue Eng Part A. 2014;20(3–4):540–52.

    CAS  PubMed  Google Scholar 

  58. Janson D, Saintigny G, Mahé C, Ghalbzouri AE. Papillary fibroblasts differentiate into reticular fibroblasts after prolonged in vitro culture. Exp Dermatol. 2013;22(1):48–53.

    Article  CAS  PubMed  Google Scholar 

  59. Janson D, Rietveld M, Mahe C, Saintigny G, El Ghalbzouri A. Differential effect of extracellular matrix derived from papillary and reticular fibroblasts on epidermal development in vitro. Eur J Dermatol. 2017;27(3):237–46.

    Article  CAS  PubMed  Google Scholar 

  60. Mine S, Fortunel NO, Pageon H, Asselineau D. Aging alters functionally human dermal papillary fibroblasts but not reticular fibroblasts: a new view of skin morphogenesis and aging. PLoS One. 2009;3(12):e4066.

    Article  CAS  Google Scholar 

  61. Pageon H, Zucchi H, Asselineau D. Distinct and complementary roles of papillary and reticular fibroblasts in skin morphogenesis and homeostasis. Eur J Dermatol. 2012;22(3):324–32.

    Article  CAS  PubMed  Google Scholar 

  62. Hill RP, Gardner A, Crawford HC, Richer R, Dodds A, Owens WA, Lawrence C, Rao S, Kara B, James SE, Jahoda CA. Human hair follicle dermal sheath and papilla cells support keratinocyte growth in monolayer coculture. Exp Dermatol. 2013;22(3):236–8.

    Article  CAS  PubMed  Google Scholar 

  63. Higgins CA, Roger MF, Hill RP, Ali-Khan AS, Garlick JA, Christiano AM, Jahoda CAB. Multifaceted role of hair follicle dermal cells in bioengineered skins. Br J Dermatol. 2017;176(5):1259–69.

    Article  CAS  PubMed  Google Scholar 

  64. Shin YH, Seo YK, Yoon HH, Yoo BY, Song KY, Park JK. Comparison of hair dermal cells and skin fibroblasts in a collagen sponge for use in wound repair. Biotechnol Bioprocess Eng. 2011;16(4):793.

    Article  CAS  Google Scholar 

  65. Cho HJ, Bae IH, Chung HJ, Kim DS, Kwon SB, Cho YJ, Youn SW, Park KC. Effects of hair follicle dermal sheath cells in the reconstruction of skin equivalents. J Dermatol Sci. 2004;35(1):74–7.

    Article  PubMed  Google Scholar 

  66. Reynolds AJ, Jahoda CA. Hair follicle stem cells? A distinct germinative epidermal cell population is activated in vitro by the presence of hair dermal papilla cells. J Cell Sci. 1991;99(2):373–85.

    Article  PubMed  Google Scholar 

  67. Tosca MC, Chlapanidas T, Galuzzi M, Antonioli B, Perteghella S, Vigani B, Mantelli M, Ingo D, Avanzini MA, Vigo D, Faustini M, Torre ML, Marazzi M. Human adipose-derived stromal cells as a feeder layer to improve keratinocyte expansion for clinical applications. Tissue Eng Regen Med. 2015;12(4):249–58.

    Article  CAS  Google Scholar 

  68. Sugiyama H, Maeda K, Yamato M, Hayashi R, Soma T, Hayashida Y, Yang J, Shirakabe M, Matsuyama A, Kikuchi A, Sawa Y, Okano T, Tano Y, Nishida K. Human adipose tissue-derived mesenchymal stem cells as a novel feeder layer for epithelial cells. J Tissue Eng Regen Med. 2008;2(7):445–9.

    Article  CAS  PubMed  Google Scholar 

  69. Huh CH, Kim SY, Cho HJ, Kim DS, Lee WH, Kwon SB, Na JI, Park KC. Effects of mesenchymal stem cells in the reconstruction of skin equivalents. J Dermatol Sci. 2007;46(3):217–20.

    Article  CAS  PubMed  Google Scholar 

  70. Alexaki VI, Simantiraki D, Panayiotopoulou M, Rasouli O, Venihaki M, Castana O, Alexakis D, Kampa M, Stathopoulos EN, Castanas E. Adipose tissue-derived mesenchymal cells support skin re-epithelialization through secretion of KGF-1 and PDGF-BB: comparison with dermal fibroblasts. Cell Transplant. 2012;21(11):2441–54.

    Article  PubMed  Google Scholar 

  71. Aoki S, Takezawa T, Uchihashi K, Sugihara H, Toda S. Non-skin mesenchymal cell types support epidermal regeneration in a mesenchymal stem cell or myofibroblast phenotype-independent manner. Pathol Int. 2009;59(6):368–75.

    Article  PubMed  Google Scholar 

  72. Aoki S, Toda S, Ando T, Sugihara H. Bone marrow stromal cells, preadipocytes, and dermal fibroblasts promote epidermal regeneration in their distinctive fashions. Mol Biol Cell. 2004;15(10):4647–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Ojeh NO, Navsaria HA. An in vitro skin model to study the effect of mesenchymal stem cells in wound healing and epidermal regeneration. J Biomed Mater Res A. 2014;102(8):2785–92.

    Article  PubMed  CAS  Google Scholar 

  74. Sugihara H, Toda S, Yonemitsu N, Watanabe K. Effects of fat cells on keratinocytes and fibroblasts in a reconstructed rat skin model using collagen gel matrix culture. Br J Dermatol. 2001;144(2):244–53.

    Article  CAS  PubMed  Google Scholar 

  75. Zieske JD, Mason VS, Wasson ME, Meunier SF, Nolte CJ, Fukai N, Olsen BR, Parenteau NL. Basement membrane assembly and differentiation of cultured corneal cells: importance of culture environment and endothelial cell interaction. Exp Cell Res. 1994;214(2):621–33.

    Article  CAS  PubMed  Google Scholar 

  76. Maas-Szabowski N, Szabowski A, Andrecht S, Kolbus A, Schorpp-Kistner M, Angel P, Fusenig NE. Organotypic cocultures with genetically modified mouse fibroblasts as a tool to dissect molecular mechanisms regulating keratinocyte growth and differentiation. J Invest Dermatol. 2001;116(5):816–20.

    Article  CAS  PubMed  Google Scholar 

  77. Maas-Szabowski N, Shimotoyodome A, Fusenig NE. Keratinocyte growth regulation in fibroblast cocultures via a double paracrine mechanism. J Cell Sci. 1999;112(Pt 12):1843–53.

    Article  PubMed  Google Scholar 

  78. Nolte SV, Xu W, Rennekampff HO, Rodemann HP. Diversity of fibroblasts—a review on implications for skin tissue engineering. Cells Tissues Organs. 2008;187(3):165–76.

    Article  PubMed  Google Scholar 

  79. Choi Y, Fuchs E. TGF-beta and retinoic acid: regulators of growth and modifiers of differentiation in human epidermal cells. Cell Regul. 1990;1(11):791–809.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Maas-Szabowski N, Stark HJ, Fusenig NE. Keratinocyte growth regulation in defined organotypic cultures through IL-1-induced keratinocyte growth factor expression in resting fibroblasts. J Invest Dermatol. 2000;114(6):1075–84.

    Article  CAS  PubMed  Google Scholar 

  81. El Ghalbzouri A, Ponec M. Diffusible factors released by fibroblasts support epidermal morphogenesis and deposition of basement membrane components. Wound Repair Regen. 2004;12(3):359–67.

    Article  PubMed  Google Scholar 

  82. Smola H, Stark HJ, Thiekotter G, Mirancea N, Krieg T, Fusenig NE. Dynamics of basement membrane formation by keratinocyte-fibroblast interactions in organotypic skin culture. Exp Cell Res. 1998;239(2):399–410.

    Article  CAS  PubMed  Google Scholar 

  83. El Ghalbzouri A, Jonkman MF, Dijkman R, Ponec M. Basement membrane reconstruction in human skin equivalents is regulated by fibroblasts and/or exogenously activated keratinocytes. J Invest Dermatol. 2005;124(1):79–86.

    Article  PubMed  Google Scholar 

  84. Lee DY, Cho KH. The effects of epidermal keratinocytes and dermal fibroblasts on the formation of cutaneous basement membrane in three-dimensional culture systems. Arch Dermatol Res. 2005;296(7):296–302.

    Article  PubMed  Google Scholar 

  85. Wong T, McGrath JA, Navsaria H. The role of fibroblasts in tissue engineering and regeneration. Br J Dermatol. 2007;156(6):1149–55.

    Article  CAS  PubMed  Google Scholar 

  86. Smola H, Thiekotter G, Baur M, Stark HJ, Breitkreutz D, Fusenig NE. Organotypic and epidermal-dermal co-cultures of normal human keratinocytes and dermal cells: regulation of transforming growth factor alpha, beta1 and beta2 mRNA levels. Toxicol In Vitro. 1994;8(4):641–50.

    Article  CAS  PubMed  Google Scholar 

  87. Konig A, Bruckner-Tuderman L. Transforming growth factor-beta stimulates collagen VII expression by cutaneous cells in vitro. J Cell Biol. 1992;117(3):679–85.

    Article  CAS  PubMed  Google Scholar 

  88. Konig A, Bruckner-Tuderman L. Transforming growth factor-beta promotes deposition of collagen VII in a modified organotypic skin model. Lab Investig. 1994;70(2):203–9.

    CAS  PubMed  Google Scholar 

  89. Varkey M, Ding J, Tredget EE. Differential collagen-glycosaminoglycan matrix remodeling by superficial and deep dermal fibroblasts: potential therapeutic targets for hypertrophic scar. Biomaterials. 2011;32(30):7581–91.

    Article  CAS  PubMed  Google Scholar 

  90. Wang J, Dodd C, Shankowsky HA, Scott PG, Tredget EE. Deep dermal fibroblasts contribute to hypertrophic scarring. Lab Investig. 2008;88(12):1278–90.

    Article  CAS  PubMed  Google Scholar 

  91. Chiu HC, Chang CH, Chen JS, Jee SH. Human hair follicle dermal papilla cell, dermal sheath cell and interstitial dermal fibroblast characteristics. J Formos Med Assoc. 1996;95(9):667–74.

    CAS  PubMed  Google Scholar 

  92. Inoue K, Aoi N, Yamauchi Y, Sato T, Suga H, Eto H, Kato H, Tabata Y, Yoshimura K. TGF-beta is specifically expressed in human dermal papilla cells and modulates hair folliculogenesis. J Cell Mol Med. 2009;13(11–12):4643–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Jimenez F, Poblet E, Izeta A. Reflections on how wound healing-promoting effects of the hair follicle can be translated into clinical practice. Exp Dermatol. 2015;24(2):91–4.

    Article  PubMed  Google Scholar 

  94. Jahoda CA, Reynolds AJ. Hair follicle dermal sheath cells: unsung participants in wound healing. Lancet. 2001;358(9291):1445–8.

    Article  CAS  PubMed  Google Scholar 

  95. Crisan M, Corselli M, Chen WC, Peault B. Perivascular cells for regenerative medicine. J Cell Mol Med. 2012;16(12):2851–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Mills SJ, Cowin AJ, Kaur P. Pericytes, mesenchymal stem cells and the wound healing process. Cell. 2013;2(3):621–34.

    Article  CAS  Google Scholar 

  97. Chen CW, Montelatici E, Crisan M, Corselli M, Huard J, Lazzari L, Péault B. Perivascular multi-lineage progenitor cells in human organs: regenerative units, cytokine sources or both? Cytokine Growth Factor Rev. 2009;20(5–6):429–34.

    Article  CAS  PubMed  Google Scholar 

  98. Sorrentino A, Ferracin M, Castelli G, Biffoni M, Tomaselli G, Baiocchi M, Fatica A, Negrini M, Peschle C, Valtieri M. Isolation and characterization of CD146+ multipotent mesenchymal stromal cells. Exp Hematol. 2008;36(8):1035–46.

    Article  CAS  PubMed  Google Scholar 

  99. Dohgu S, Banks WA. Brain pericytes increase the lipopolysaccharide-enhanced transcytosis of HIV-1 free virus across the in vitro blood-brain barrier: evidence for cytokine-mediated pericyte-endothelial cell crosstalk. Fluids Barriers CNS. 2013;10(1):23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Walter MN, Wright KT, Fuller HR, MacNeil S, Johnson WE. Mesenchymal stem cell-conditioned medium accelerates skin wound healing: an in vitro study of fibroblast and keratinocyte scratch assays. Exp Cell Res. 2010;316(7):1271–81.

    Article  CAS  PubMed  Google Scholar 

  101. Isakson M, de Blacam C, Whelan D, McArdle A, Clover AJP. Mesenchymal stem cells and cutaneous wound healing: current evidence and future potential. Stem Cells Int. 2015;2015:12.

    Article  Google Scholar 

  102. Ghieh F, Jurjus R, Ibrahim A, Geagea AG, Daouk H, El Baba B, Chams S, Matar M, Zein W, Jurjus A. The use of stem cells in burn wound healing: a review. Biomed Res Int. 2015;2015:9.

    Article  CAS  Google Scholar 

  103. Wu Y, Zhao RC, Tredget EE. Concise review: bone marrow-derived stem/progenitor cells in cutaneous repair and regeneration. Stem Cells. 2010;28(5):905–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Black AF, Berthod F, L’Heureux N, Germain L, Auger FA. In vitro reconstruction of a human capillary-like network in a tissue-engineered skin equivalent. FASEB J. 1998;12(13):1331–40.

    Article  CAS  PubMed  Google Scholar 

  105. Marino D, Luginbuhl J, Scola S, Meuli M, Reichmann E. Bioengineering dermo-epidermal skin grafts with blood and lymphatic capillaries. Sci Transl Med. 2014;6(221):221ra14.

    Article  PubMed  CAS  Google Scholar 

  106. Chau DY, Johnson C, MacNeil S, Haycock JW, Ghaemmaghami AM. The development of a 3D immunocompetent model of human skin. Biofabrication. 2013;5(3):035011.

    Article  CAS  PubMed  Google Scholar 

  107. Mai J, Virtue A, Shen J, Wang H, Yang XF. An evolving new paradigm: endothelial cells—conditional innate immune cells. J Hematol Oncol. 2013;6:61.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  108. Banchereau J, Briere F, Caux C, Davoust J, Lebecque S, Liu YJ, Pulendran B, Palucka K. Immunobiology of dendritic cells. Ann Rev Immunol. 2000;18(1):767–811.

    Article  CAS  Google Scholar 

  109. Sorrell JM, Baber MA, Caplan AI. Human dermal fibroblast subpopulations; differential interactions with vascular endothelial cells in coculture: nonsoluble factors in the extracellular matrix influence interactions. Wound Repair Regen. 2008;16(2):300–9.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Epithelial Stem Cell Biology Group, School of Biomedical Sciences, Curtin University, Perth, WA, Australia

    Joanne K. Gardner, Zalitha Pieterse & Pritinder Kaur

  2. Curtin Health and Innovation Research Institute, Curtin University, Perth, WA, Australia

    Joanne K. Gardner, Zalitha Pieterse & Pritinder Kaur

Authors
  1. Joanne K. Gardner
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  2. Zalitha Pieterse
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  3. Pritinder Kaur
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Correspondence to Pritinder Kaur .

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Editors and Affiliations

  1. Department for Plastic Surgery and Hand Surgery, Division of Experimental Plastic Surgery, Technical University of Munich, Munich, Germany

    Dominik Duscher

  2. Private Practice, Tustin, CA, USA

    Melvin A. Shiffman

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Gardner, J.K., Pieterse, Z., Kaur, P. (2019). Mesenchymal Cells that Support Human Skin Regeneration. In: Duscher, D., Shiffman, M.A. (eds) Regenerative Medicine and Plastic Surgery. Springer, Cham. https://doi.org/10.1007/978-3-030-19962-3_7

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