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Invited review article| Volume 57, ISSUE 1, P2-11, January 2010

Review of hair follicle dermal cells

  • Chao-Chun Yang
    Affiliations
    Department of Dermatology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA

    Department of Dermatology, School of Medicine, National Cheng Kung University, Tainan 704, Taiwan

    Institute of Clinical Medicine, School of Medicine, National Cheng Kung University, Tainan 704, Taiwan
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  • George Cotsarelis
    Correspondence
    Corresponding author. Tel.: +1 215 898 9967; fax: +1 215 573 9102.
    Affiliations
    Department of Dermatology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
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      Abstract

      Hair follicle stem cells in the epithelial bulge are responsible for the continual regeneration of the hair follicle during cycling. The bulge cells reside in a niche composed of dermal cells. The dermal compartment of the hair follicle consists of the dermal papilla and dermal sheath. Interactions between hair follicle epithelial and dermal cells are necessary for hair follicle morphogenesis during development and in hair reconstitution assays. Dermal papilla and dermal sheath cells express specific markers and possess distinctive morphology and behavior in culture. These cells can induce hair follicle differentiation in epithelial cells and are required in hair reconstitution assays either in the form of intact tissue, dissociated freshly prepared cells or cultured cells. This review will focus on hair follicle dermal cells since most therapeutic efforts to date have concentrated on this aspect of the hair follicle, with the idea that enriching hair-inductive dermal cell populations and expanding their number by culture while maintaining their properties, will establish an efficient hair reconstitution assay that could eventually have therapeutic implications.

      Keywords

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      References

        • Cotsarelis G.
        Epithelial stem cells: a folliculocentric view.
        J Invest Dermatol. 2006; 126: 1459-1468
        • Millar S.E.
        Molecular mechanisms regulating hair follicle development.
        J Invest Dermatol. 2002; 118: 216-225
        • Chuong C.M.
        • Cotsarelis G.
        • Stenn K.
        Defining hair follicles in the age of stem cell bioengineering.
        J Invest Dermatol. 2007; 127: 2098-2100
        • Paus R.
        • Cotsarelis G.
        The biology of hair follicles.
        N Engl J Med. 1999; 341: 491-497
        • Ito M.
        • Sato Y.
        Dynamic ultrastructural changes of the connective tissue sheath of human hair follicles during hair cycle.
        Arch Dermatol Res. 1990; 282: 434-441
        • Fernandes K.J.
        • McKenzie I.A.
        • Mill P.
        • Smith K.M.
        • Akhavan M.
        • Barnabe-Heider F.
        • et al.
        A dermal niche for multipotent adult skin-derived precursor cells.
        Nat Cell Biol. 2004; 6: 1082-1093
        • Driskell R.R.
        • Giangreco A.
        • Jensen K.B.
        • Mulder K.W.
        • Watt F.M.
        Sox2-positive dermal papilla cells specify hair follicle type in mammalian epidermis.
        Development. 2009; 136: 2815-2823
        • Rendl M.
        • Lewis L.
        • Fuchs E.
        Molecular dissection of mesenchymal–epithelial interactions in the hair follicle.
        PLoS Biol. 2005; 3: e331
        • Tobin D.J.
        • Gunin A.
        • Magerl M.
        • Handijski B.
        • Paus R.
        Plasticity and cytokinetic dynamics of the hair follicle mesenchyme: implications for hair growth control.
        J Invest Dermatol. 2003; 120: 895-904
        • Ito M.
        • Liu Y.
        • Yang Z.
        • Nguyen J.
        • Liang F.
        • Morris R.J.
        • et al.
        Stem cells in the hair follicle bulge contribute to wound repair but not to homeostasis of the epidermis.
        Nat Med. 2005; 11: 1351-1354
        • Horne K.A.
        • Jahoda C.A.
        Restoration of hair growth by surgical implantation of follicular dermal sheath.
        Development. 1992; 116: 563-571
        • Reynolds A.J.
        • Lawrence C.
        • Cserhalmi-Friedman P.B.
        • Christiano A.M.
        • Jahoda C.A.
        Trans-gender induction of hair follicles.
        Nature. 1999; 402: 33-34
        • McElwee K.J.
        • Kissling S.
        • Wenzel E.
        • Huth A.
        • Hoffmann R.
        Cultured peribulbar dermal sheath cells can induce hair follicle development and contribute to the dermal sheath and dermal papilla.
        J Invest Dermatol. 2003; 121: 1267-1275
        • Oliver R.F.
        Whisker growth after removal of the dermal papilla and lengths of follicle in the hooded rat.
        J Embryol Exp Morphol. 1966; 15: 331-347
        • Jahoda C.A.
        Cell movement in the hair follicle dermis—more than a two-way street?.
        J Invest Dermatol. 2003; 121: ix-xi
        • Feutz A.C.
        • Barrandon Y.
        • Monard D.
        Control of thrombin signaling through PI3K is a mechanism underlying plasticity between hair follicle dermal sheath and papilla cells.
        J Cell Sci. 2008; 121: 1435-1443
        • Paus R.
        • Muller-Rover S.
        • Van Der Veen C.
        • Maurer M.
        • Eichmuller S.
        • Ling G.
        • et al.
        A comprehensive guide for the recognition and classification of distinct stages of hair follicle morphogenesis.
        J Invest Dermatol. 1999; 113: 523-532
        • Ito M.
        • Kizawa K.
        • Hamada K.
        • Cotsarelis G.
        Hair follicle stem cells in the lower bulge form the secondary germ, a biochemically distinct but functionally equivalent progenitor cell population, at the termination of catagen.
        Differentiation. 2004; 72: 548-557
        • Schmidt-Ullrich R.
        • Paus R.
        Molecular principles of hair follicle induction and morphogenesis.
        Bioessays. 2005; 27: 247-261
        • Andl T.
        • Reddy S.T.
        • Gaddapara T.
        • Millar S.E.
        WNT signals are required for the initiation of hair follicle development.
        Dev Cell. 2002; 2: 643-653
        • Petiot A.
        • Conti F.J.
        • Grose R.
        • Revest J.M.
        • Hodivala-Dilke K.M.
        • Dickson C.
        A crucial role for Fgfr2-IIIb signalling in epidermal development and hair follicle patterning.
        Development. 2003; 130: 5493-5501
        • Botchkarev V.A.
        • Botchkareva N.V.
        • Roth W.
        • Nakamura M.
        • Chen L.H.
        • Herzog W.
        • et al.
        Noggin is a mesenchymally derived stimulator of hair-follicle induction.
        Nat Cell Biol. 1999; 1: 158-164
        • Chiang C.
        • Swan R.Z.
        • Grachtchouk M.
        • Bolinger M.
        • Litingtung Y.
        • Robertson E.K.
        • et al.
        Essential role for Sonic hedgehog during hair follicle morphogenesis.
        Dev Biol. 1999; 205: 1-9
        • St-Jacques B.
        • Dassule H.R.
        • Karavanova I.
        • Botchkarev V.A.
        • Li J.
        • Danielian P.S.
        • et al.
        Sonic hedgehog signaling is essential for hair development.
        Curr Biol. 1998; 8: 1058-1068
        • Karlsson L.
        • Bondjers C.
        • Betsholtz C.
        Roles for PDGF-A and sonic hedgehog in development of mesenchymal components of the hair follicle.
        Development. 1999; 126: 2611-2621
        • Lehman J.M.
        • Laag E.
        • Michaud E.J.
        • Yoder B.K.
        An essential role for dermal primary cilia in hair follicle morphogenesis.
        J Invest Dermatol. 2008;
        • Gao J.
        • DeRouen M.C.
        • Chen C.H.
        • Nguyen M.
        • Nguyen N.T.
        • Ido H.
        • et al.
        Laminin-511 is an epithelial message promoting dermal papilla development and function during early hair morphogenesis.
        Genes Dev. 2008; 22: 2111-2124
        • Jahoda C.
        • Oliver R.F.
        The growth of vibrissa dermal papilla cells in vitro.
        Br J Dermatol. 1981; 105: 623-627
        • Messenger A.G.
        The culture of dermal papilla cells from human hair follicles.
        Br J Dermatol. 1984; 110: 685-689
        • Osada A.
        • Iwabuchi T.
        • Kishimoto J.
        • Hamazaki T.S.
        • Okochi H.
        Long-term culture of mouse vibrissa dermal papilla cells and de novo hair follicle induction.
        Tissue Eng. 2007; 13: 975-982
        • Wu J.J.
        • Liu R.Q.
        • Lu Y.G.
        • Zhu T.Y.
        • Cheng B.
        • Men X.
        Enzyme digestion to isolate and culture human scalp dermal papilla cells: a more efficient method.
        Arch Dermatol Res. 2005; 297: 60-67
        • Kishimoto J.
        • Ehama R.
        • Wu L.
        • Jiang S.
        • Jiang N.
        • Burgeson R.E.
        Selective activation of the versican promoter by epithelial–mesenchymal interactions during hair follicle development.
        Proc Natl Acad Sci USA. 1999; 96: 7336-7341
        • Fujie T.
        • Katoh S.
        • Oura H.
        • Urano Y.
        • Arase S.
        The chemotactic effect of a dermal papilla cell-derived factor on outer root sheath cells.
        J Dermatol Sci. 2001; 25: 206-212
        • Iida M.
        • Ihara S.
        • Matsuzaki T.
        Hair cycle-dependent changes of alkaline phosphatase activity in the mesenchyme and epithelium in mouse vibrissa follicles.
        Dev Growth Differ. 2007; 49: 185-195
        • Handjiski B.K.
        • Eichmuller S.
        • Hofmann U.
        • Czarnetzki B.M.
        • Paus R.
        Alkaline phosphatase activity and localization during the murine hair cycle.
        Br J Dermatol. 1994; 131: 303-310
        • Rendl M.
        • Polak L.
        • Fuchs E.
        BMP signaling in dermal papilla cells is required for their hair follicle-inductive properties.
        Genes Dev. 2008; 22: 543-557
        • Jahoda C.A.
        • Reynolds A.J.
        • Chaponnier C.
        • Forester J.C.
        • Gabbiani G.
        Smooth muscle alpha-actin is a marker for hair follicle dermis in vivo and in vitro.
        J Cell Sci. 1991; 99: 627-636
        • Soma T.
        • Tajima M.
        • Kishimoto J.
        Hair cycle-specific expression of versican in human hair follicles.
        J Dermatol Sci. 2005; 39: 147-154
        • Kim S.R.
        • Cha S.Y.
        • Kim M.K.
        • Kim J.C.
        • Sung Y.K.
        Induction of versican by ascorbic acid 2-phosphate in dermal papilla cells.
        J Dermatol Sci. 2006; 43: 60-62
        • Enshell-Seijffers D.
        • Lindon C.
        • Morgan B.A.
        The serine protease Corin is a novel modifier of the Agouti pathway.
        Development. 2008; 135: 217-225
        • Ito Y.
        • Hamazaki T.S.
        • Ohnuma K.
        • Tamaki K.
        • Asashima M.
        • Okochi H.
        Isolation of murine hair-inducing cells using the cell surface marker prominin-1/CD133.
        J Invest Dermatol. 2007; 127: 1052-1060
        • Oliver R.F.
        The experimental induction of whisker growth in the hooded rat by implantation of dermal papillae.
        J Embryol Exp Morphol. 1967; 18: 43-51
        • Oliver R.F.
        The induction of hair follicle formation in the adult hooded rat by vibrissa dermal papillae.
        J Embryol Exp Morphol. 1970; 23: 219-236
        • Jahoda C.A.
        • Horne K.A.
        • Oliver R.F.
        Induction of hair growth by implantation of cultured dermal papilla cells.
        Nature. 1984; 311: 560-562
        • Jahoda C.A.
        • Oliver R.F.
        • Reynolds A.J.
        • Forrester J.C.
        • Gillespie J.W.
        • Cserhalmi-Friedman P.B.
        • et al.
        Trans-species hair growth induction by human hair follicle dermal papillae.
        Exp Dermatol. 2001; 10: 229-237
        • Paus R.
        • Ito N.
        • Takigawa M.
        • Ito T.
        The hair follicle and immune privilege.
        J Investig Dermatol Symp Proc. 2003; 8: 188-194
        • Iida M.
        • Ihara S.
        • Matsuzaki T.
        Follicular epithelia and dermal papillae of mouse vibrissa follicles qualitatively change their hair-forming ability during anagen.
        Differentiation. 2007; 75: 371-381
        • Inamatsu M.
        • Tochio T.
        • Makabe A.
        • Endo T.
        • Oomizu S.
        • Kobayashi E.
        • et al.
        Embryonic dermal condensation and adult dermal papilla induce hair follicles in adult glabrous epidermis through different mechanisms.
        Dev Growth Differ. 2006; 48: 73-86
        • Osada A.
        • Kobayashi K.
        • Masui S.
        • Hamazaki T.S.
        • Yasuda K.
        • Okochi H.
        Cloned cells from the murine dermal papilla have hair-inducing ability.
        J Dermatol Sci. 2009; 54: 129-131
        • Reynolds A.J.
        • Jahoda C.A.
        Cultured dermal papilla cells induce follicle formation and hair growth by transdifferentiation of an adult epidermis.
        Development. 1992; 115: 587-593
        • Jahoda C.A.
        Induction of follicle formation and hair growth by vibrissa dermal papillae implanted into rat ear wounds: vibrissa-type fibres are specified.
        Development. 1992; 115: 1103-1109
        • Lichti U.
        • Anders J.
        • Yuspa S.H.
        Isolation and short-term culture of primary keratinocytes, hair follicle populations and dermal cells from newborn mice and keratinocytes from adult mice for in vitro analysis and for grafting to immunodeficient mice.
        Nat Protoc. 2008; 3: 799-810
        • Ehama R.
        • Ishimatsu-Tsuji Y.
        • Iriyama S.
        • Ideta R.
        • Soma T.
        • Yano K.
        • et al.
        Hair follicle regeneration using grafted rodent and human cells.
        J Invest Dermatol. 2007; 127: 2106-2115
        • Morris R.J.
        • Liu Y.
        • Marles L.
        • Yang Z.
        • Trempus C.
        • Li S.
        • et al.
        Capturing and profiling adult hair follicle stem cells.
        Nat Biotechnol. 2004; 22: 411-417
        • Zheng Y.
        • Du X.
        • Wang W.
        • Boucher M.
        • Parimoo S.
        • Stenn K.
        Organogenesis from dissociated cells: generation of mature cycling hair follicles from skin-derived cells.
        J Invest Dermatol. 2005; 124: 867-876
        • Havlickova B.
        • Biro T.
        • Mescalchin A.
        • Arenberger P.
        • Paus R.
        Towards optimization of an organotypic assay system that imitates human hair follicle-like epithelial–mesenchymal interactions.
        Br J Dermatol. 2004; 151: 753-765
        • Qiao J.
        • Turetsky A.
        • Kemp P.
        • Teumer J.
        Hair morphogenesis in vitro: formation of hair structures suitable for implantation.
        Regen Med. 2008; 3: 683-692
        • Nakao K.
        • Morita R.
        • Saji Y.
        • Ishida K.
        • Tomita Y.
        • Ogawa M.
        • et al.
        The development of a bioengineered organ germ method.
        Nat Methods. 2007; 4: 227-230
        • Horne K.A.
        • Jahoda C.A.
        • Oliver R.F.
        Whisker growth induced by implantation of cultured vibrissa dermal papilla cells in the adult rat.
        J Embryol Exp Morphol. 1986; 97: 111-124
        • Young T.H.
        • Lee C.Y.
        • Chiu H.C.
        • Hsu C.J.
        • Lin S.J.
        Self-assembly of dermal papilla cells into inductive spheroidal microtissues on poly(ethylene-co-vinyl alcohol) membranes for hair follicle regeneration.
        Biomaterials. 2008; 29: 3521-3530
        • Young T.H.
        • Tu H.R.
        • Chan C.C.
        • Huang Y.C.
        • Yen M.H.
        • Cheng N.C.
        • et al.
        The enhancement of dermal papilla cell aggregation by extracellular matrix proteins through effects on cell-substratum adhesivity and cell motility.
        Biomaterials. 2009;
        • Kishimoto J.
        • Burgeson R.E.
        • Morgan B.A.
        Wnt signaling maintains the hair-inducing activity of the dermal papilla.
        Genes Dev. 2000; 14: 1181-1185
        • Ouji Y.
        • Yoshikawa M.
        • Shiroi A.
        • Ishizaka S.
        Promotion of hair follicle development and trichogenesis by Wnt-10b in cultured embryonic skin and in reconstituted skin.
        Biochem Biophys Res Commun. 2006; 345: 581-587
        • Yamauchi K.
        • Kurosaka A.
        Inhibition of glycogen synthase kinase-3 enhances the expression of alkaline phosphatase and insulin-like growth factor-1 in human primary dermal papilla cell culture and maintains mouse hair bulbs in organ culture.
        Arch Dermatol Res. 2009; 301: 357-365
        • Kwack M.H.
        • Sung Y.K.
        • Chung E.J.
        • Im S.U.
        • Ahn J.S.
        • Kim M.K.
        • et al.
        Dihydrotestosterone-inducible dickkopf 1 from balding dermal papilla cells causes apoptosis in follicular keratinocytes.
        J Invest Dermatol. 2008; 128: 262-269
        • Kitagawa T.
        • Matsuda K.
        • Inui S.
        • Takenaka H.
        • Katoh N.
        • Itami S.
        • et al.
        Keratinocyte growth inhibition through the modification of Wnt signaling by androgen in balding dermal papilla cells.
        J Clin Endocrinol Metab. 2009; 94: 1288-1294
        • Inui S.
        • Fukuzato Y.
        • Nakajima T.
        • Yoshikawa K.
        • Itami S.
        Androgen-inducible TGF-beta1 from balding dermal papilla cells inhibits epithelial cell growth: a clue to understand paradoxical effects of androgen on human hair growth.
        FASEB J. 2002; 16: 1967-1969
        • Hamada K.
        • Randall V.A.
        Inhibitory autocrine factors produced by the mesenchyme-derived hair follicle dermal papilla may be a key to male pattern baldness.
        Br J Dermatol. 2006; 154: 609-618
        • Bahta A.W.
        • Farjo N.
        • Farjo B.
        • Philpott M.P.
        Premature senescence of balding dermal papilla cells in vitro is associated with p16(INK4a) expression.
        J Invest Dermatol. 2008; 128: 1088-1094
        • Jahoda C.A.
        • Reynolds A.J.
        • Oliver R.F.
        Induction of hair growth in ear wounds by cultured dermal papilla cells.
        J Invest Dermatol. 1993; 101: 584-590
        • Weinberg W.C.
        • Goodman L.V.
        • George C.
        • Morgan D.L.
        • Ledbetter S.
        • Yuspa S.H.
        • et al.
        Reconstitution of hair follicle development in vivo: determination of follicle formation, hair growth, and hair quality by dermal cells.
        J Invest Dermatol. 1993; 100: 229-236
        • Lichti U.
        • Weinberg W.C.
        • Goodman L.
        • Ledbetter S.
        • Dooley T.
        • Morgan D.
        • et al.
        In vivo regulation of murine hair growth: insights from grafting defined cell populations onto nude mice.
        J Invest Dermatol. 1993; 101: 124S-129S
        • Jahoda C.A.
        • Oliver R.F.
        • Reynolds A.J.
        • Forrester J.C.
        • Horne K.A.
        Human hair follicle regeneration following amputation and grafting into the nude mouse.
        J Invest Dermatol. 1996; 107: 804-807
        • Reynolds A.J.
        • Jahoda C.A.
        Cultured human and rat tooth papilla cells induce hair follicle regeneration and fiber growth.
        Differentiation. 2004; 72: 566-575
        • Qiao J.
        • Philips E.
        • Teumer J.
        A graft model for hair development.
        Exp Dermatol. 2008; 17: 512-518

      Biography

      Dr. Chao-Chun Yang is doing his postdoctoral research in Dr. George Cotsarelis’ laboratory in University of Pennsylvania, USA since 2008. He received his MD degree in National Cheng Kung University, Tainan, Taiwan in 1999. After finishing residency training, he served as an attending physician and ran the hair clinics in the Department of Dermatology, National Cheng Kung University Hospital, Tainan, Taiwan since 2005. His current research is focused on developing hair reconstitution assays.

      Biography

      George Cotsarelis (MD) is the Albert M. Kligman Professor of dermatology at the University of Pennsylvania School of Medicine in Philadelphia where he is the Director of the Hair and Scalp Clinic and Director of the Program on Epithelial Regeneration and Stem Cells, University of Pennsylvania Institute for Regenerative Medicine. He received his MD from the University of Pennsylvania School of Medicine, where he also completed his Dermatology Residency and a Howard Hughes sponsored Fellowship for Physicians in molecular biology. He is the first to identified and localized stem cells in the hair follicles of both mice and humans. The hair follicle stem cells are located in a unique area called the bulge. Since the identification of these cells, he has developed means for isolating, characterizing and manipulating them. He first demonstrated that isolated hair follicle stem cells could generate new hair follicles when injected into immunodeficient mice. His research areas of interest include epithelial stem cells, hair follicle biology, wound healing and skin regeneration.