Skip to main content
SpringerLink
Log in

Stem Cells and Hair Follicle Cloning/Engineering

  • Chapter
  • First Online:
Androgenetic Alopecia From A to Z

  • 391 Accesses

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 129.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Cotsarelis G. Epithelial stem cells: a folliculocentric view. J Invest Dermatol. 2006;126(7):1459–68.

    CAS  PubMed  Google Scholar 

  2. Stenn KS, Cotsarelis G. Bioengineering the hair follicle: fringe benefits of stem cell technology. Curr Opin Biotechnol. 2005;16(5):493–7.

    CAS  PubMed  Google Scholar 

  3. Strong AL, Neumeister MW, Levi B. Stem cells and tissue engineering: regeneration of the skin and its contents. Clin Plast Surg. 2017;44(3):635–50.

    PubMed  PubMed Central  Google Scholar 

  4. Toma JG, Akhavan M, Fernandes KJ, Barnabé-Heider F, Sadikot A, Kaplan DR, Miller FD. Isolation of multipotent adult stem cells from the dermis of mammalian skin. Nat Cell Biol. 2001;3(9):778–84.

    CAS  PubMed  Google Scholar 

  5. Reed M. Hair transplantation. In: Thorne CH, Beasley RW, Aston SJ, Bartlett SP, Gurtner GC, Spear SL, editors. Grabb and Smith’s plastic surgery. 6th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2006. p. 562–72.

    Google Scholar 

  6. Cooley J. Follicular cell implantation: an update on “hair follicle cloning”. Facial Plast Surg Clin North Am. 2004;12(2):219–24.

    PubMed  Google Scholar 

  7. Martinez-Lopez A, Montero-Vilchez T, Sierra-Sánchez Á, Molina-Leyva A, Arias-Santiago S. Advanced medical therapies in the management of non-scarring alopecia: areata and androgenic alopecia. Int J Mol Sci. 2020;21(21):8390.

    CAS  PubMed  PubMed Central  Google Scholar 

  8. EudraLex the rules governing medicinal products in the European Union Volume 4. Guidelines on good manufacturing practice specific to advanced therapy medicinal products. https://ec.europa.eu/health/sites/health/files/files/eudralex/vol-4/2017_11_22_guidelines_gmp_for_atmps.pdf. Accessed 30 May 2021.

  9. Maxson S, Lopez EA, Yoo D, Danilkovitch-Miagkova A, Leroux MA. Concise review: role of mesenchymal stem cells in wound repair. Stem Cells Transl Med. 2012;1(2):142–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Regulation (EC) No 1394/2007 of the European Parliament and of the Council of 13 November 2007 on Advanced Therapy Medicinal Products and Amending Directive 2001/83/EC and Regulation (EC) No 726/2004. [(accessed on 30 May 2021)]; Available online:https://ec.europa.eu/health/sites/default/files/files/eudralex/vol-1/reg_2007_1394/reg_2007_1394_en.pdf

  11. Stenn KS, Paus R. Controls of hair follicle cycling. Physiol Rev. 2001;81(1):449–94.

    CAS  PubMed  Google Scholar 

  12. Yang CC, Cotsarelis G. Review of hair follicle dermal cells. J Dermatol Sci. 2010;57(1):2–11.

    PubMed  PubMed Central  Google Scholar 

  13. Zheng Y, Nace A, Chen W, Watkins K, Sergott L, Homan Y, Vandeberg JL, Breen M, Stenn K. Mature hair follicles generated from dissociated cells: a universal mechanism of folliculoneogenesis. Dev Dyn. 2010;239(10):2619–26.

    PubMed  Google Scholar 

  14. Rose K. The beginning of the age of mammals. Baltimore: Johns Hopkins University Press; 2006. 428 p.

    Google Scholar 

  15. Botchkarev VA, Paus R. Molecular biology of hair morphogenesis: development and cycling. J Exp Zool B Mol Dev Evol. 2003;298(1):164–80.

    PubMed  Google Scholar 

  16. Millar SE. Molecular mechanisms regulating hair follicle development. J Invest Dermatol. 2002;118(2):216–25.

    CAS  PubMed  Google Scholar 

  17. Philpott M, Paus R. Principles of hair follicle morphogenesis. In: Chuong CM, editor. Molecular basis of epithelial appendage morphogenesis. Austin: Landes; 1998. p. 75–110.

    Google Scholar 

  18. Oro AE, Scott MP. Splitting hairs: dissecting roles of signaling systems in epidermal development. Cell. 1998;95(5):575–8.

    CAS  PubMed  Google Scholar 

  19. Ji S, Zhu Z, Sun X, Fu X. Functional hair follicle regeneration: an updated review. Signal Transduct Target Ther. 2021;6(1):66.

    PubMed  PubMed Central  Google Scholar 

  20. Sato T, Vries RG, Snippert HJ, van de Wetering M, Barker N, Stange DE, van Es JH, Abo A, Kujala P, Peters PJ, Clevers H. Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature. 2009;459(7244):262–5.

    CAS  PubMed  Google Scholar 

  21. Shackleton M, Vaillant F, Simpson KJ, Stingl J, Smyth GK, Asselin-Labat ML, Wu L, Lindeman GJ, Visvader JE. Generation of a functional mammary gland from a single stem cell. Nature. 2006;439(7072):84–8.

    CAS  PubMed  Google Scholar 

  22. Ikeda E, Morita R, Nakao K, et al. Fully functional bioengineered tooth replacement as an organ replacement therapy. Proc Natl Acad Sci U S A. 2009;106(32):13475–80.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Garza LA, Yang CC, Zhao T, Cotsarelis G, et al. Bald scalp in men with androgenetic alopecia retains hair follicle stem cells but lacks CD200-rich and CD34-positive hair follicle progenitor cells. J Clin Invest. 2011;121(2):613–22.

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Benitah SA, Frye M, Glogauer M, Watt FM. Stem cell depletion through epidermal deletion of Rac1. Science. 2005;309(5736):933–5.

    PubMed  Google Scholar 

  25. Dlugosz AA, Hutchin ME. From hair to eternity: Hedgehog signaling in skin biology and cancer. Prog Dermatol. 2005;39:1–12.

    Google Scholar 

  26. Yi R, O’Carroll D, Pasolli HA, Zhang Z, Dietrich FS, Tarakhovsky A, Fuchs E. Morphogenesis in skin is governed by discrete sets of differentially expressed microRNAs. Nat Genet. 2006;38(3):356–62.

    CAS  PubMed  Google Scholar 

  27. Chuong CM, Cotsarelis G, Stenn K. Defining hair follicles in the age of stem cell bioengineering. J Invest Dermatol. 2007;127(9):2098–100.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Ohyama M, Zheng Y, Paus R, Stenn KS. The mesenchymal component of hair follicle neogenesis: background, methods and molecular characterization. Exp Dermatol. 2010;19(2):89–99.

    PubMed  Google Scholar 

  29. Cohen J. The transplantation of individual rat and guineapig whisker papillae. J Embryol Exp Morphol. 1961;9:117–27.

    CAS  PubMed  Google Scholar 

  30. Oliver RF. The experimental induction of whisker growth in the hooded rat by implantation of dermal papillae. J Embryol Exp Morphol. 1967;18(1):43–51.

    CAS  PubMed  Google Scholar 

  31. Jahoda CA. Induction of follicle formation and hair growth by vibrissa dermal papillae implanted into rat ear wounds: vibrissa-type fibres are specified. Development. 1992;115(4):1103–9.

    CAS  PubMed  Google Scholar 

  32. Oliver RF. The induction of hair follicle formation in the adult hooded rat by vibrissa dermal papillae. J Embryol Exp Morphol. 1970;23(1):219–36.

    CAS  PubMed  Google Scholar 

  33. Aoi N, Inoue K, Kato H, et al. Clinically applicable transplantation procedure of dermal papilla cells for hair follicle 29 regeneration. J Tissue Eng Regen Med. 2012;6(2):85–95.

    PubMed  Google Scholar 

  34. Jahoda CA, Horne KA, Oliver RF. Induction of hair growth by implantation of cultured dermal papilla cells. Nature. 1984;311(5986):560–2.

    CAS  PubMed  Google Scholar 

  35. Jahoda CA, Reynolds AJ, Oliver RF. Induction of hair growth in ear wounds by cultured dermal papilla cells. J Invest Dermatol. 1993;101(4):584–90.

    CAS  PubMed  Google Scholar 

  36. McElwee KJ, 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(6):1267–75.

    CAS  PubMed  Google Scholar 

  37. Reynolds AJ, Lawrence C, Cserhalmi-Friedman PB, Christiano AM, Jahoda CA. Trans-gender induction of hair follicles. Nature. 1999;402(6757):33–4.

    CAS  PubMed  Google Scholar 

  38. Lichti U, Weinberg WC, Goodman L, Ledbetter S, Dooley T, Morgan D, Yuspa SH. In vivo regulation of murine hair growth: insights from grafting defined cell populations onto nude mice. J Invest Dermatol. 1993;101(1 Suppl):124S–9S.

    CAS  PubMed  Google Scholar 

  39. Weinberg WC, Goodman LV, George C, 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(3):229–36.

    CAS  PubMed  Google Scholar 

  40. Kamimura J, Lee D, Baden HP, Brissette J, Dotto GP. Primary mouse keratinocyte cultures contain hair follicle progenitor cells with multiple differentiation potential. J Invest Dermatol. 1997;109(4):534–40.

    CAS  PubMed  Google Scholar 

  41. Kishimoto J, Ehama R, Wu L, Jiang S, Jiang N, Burgeson RE. Selective activation of the versican promoter by epithelial-mesenchymal interactions during hair follicle development. Proc Natl Acad Sci U S A. 1999;96(13):7336–41.

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Ehama R, Ishimatsu-Tsuji Y, Iriyama S, Ideta R, Soma T, Yano K, Kawasaki C, Suzuki S, Shirakata Y, Hashimoto K, Kishimoto J. Hair follicle regeneration using grafted rodent and human cells. J Invest Dermatol. 2007;127(9):2106–15.

    CAS  PubMed  Google Scholar 

  43. Reynolds AJ, Jahoda CA. Cultured dermal papilla cells induce follicle formation and hair growth by transdifferentiation of an adult epidermis. Development. 1992;115(2):587–93.

    CAS  PubMed  Google Scholar 

  44. Inoue K, Kato H, Sato T, Osada A, Aoi N, Suga H, Eto H, Gonda K, Yoshimura K. Evaluation of animal models for the hair-inducing capacity of cultured human dermal papilla cells. Cells Tissues Organs. 2009;190(2):102–10.

    PubMed  Google Scholar 

  45. Inamatsu M, Matsuzaki T, Iwanari H, Yoshizato K. Establishment of rat dermal papilla cell lines that sustain the potency to induce hair follicles from afollicular skin. J Invest Dermatol. 1998;111(5):767–75.

    CAS  PubMed  Google Scholar 

  46. Osada A, Iwabuchi T, Kishimoto J, Hamazaki TS, Okochi H. Long-term culture of mouse vibrissal dermal papilla cells and de novo hair follicle induction. Tissue Eng. 2007;13(5):975–82.

    CAS  PubMed  Google Scholar 

  47. Qiao J, Philips E, Teumer J. A graft model for hair development. Exp Dermatol. 2008;17(6):512–8.

    PubMed  Google Scholar 

  48. Qiao J, Zawadzka A, Philips E, Turetsky A, Batchelor S, Peacock J, Durrant S, Garlick D, Kemp P, Teumer J. Hair follicle neogenesis induced by cultured human scalp dermal papilla cells. Regen Med. 2009;4(5):667–76.

    PubMed  Google Scholar 

  49. Ito Y, Hamazaki TS, 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(5):1052–60.

    CAS  PubMed  Google Scholar 

  50. 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(5):867–76.

    CAS  PubMed  Google Scholar 

  51. Blanpain C, Lowry WE, Geoghegan A, Polak L, Fuchs E. Self-renewal, multipotency, and the existence of two cell populations within an epithelial stem cell niche. Cell. 2004;118(5):635–48.

    CAS  PubMed  Google Scholar 

  52. Morris RJ, Liu Y, Marles L, Yang Z, Trempus C, Li S, Lin JS, Sawicki JA, Cotsarelis G. Capturing and profiling adult hair follicle stem cells. Nat Biotechnol. 2004;22(4):411–7.

    CAS  PubMed  Google Scholar 

  53. Oliver RF. Whisker growth after removal of the dermal papilla and lengths of follicle in the hooded rat. J Embryol Exp Morphol. 1966;15(3):331–47.

    CAS  PubMed  Google Scholar 

  54. Oliver RF. Histological studies of whisker regeneration in the hooded rat. J Embryol Exp Morphol. 1966;16(2):231–44.

    CAS  PubMed  Google Scholar 

  55. Horne KA, Jahoda CA. Restoration of hair growth by surgical implantation of follicular dermal sheath. Development. 1992;116(3):563–71.

    CAS  PubMed  Google Scholar 

  56. Paus R, Nickoloff BJ, Ito T. A ‘hairy’ privilege. Trends Immunol. 2005;26(1):32–40.

    CAS  PubMed  Google Scholar 

  57. Itami S, Kurata S, Takayasu S. Androgen induction of follicular epithelial cell growth is mediated via insulin-like growth factor-I from dermal papilla cells. Biochem Biophys Res Commun. 1995;212(3):988–94.

    CAS  PubMed  Google Scholar 

  58. Rosenquist TA, Martin GR. Fibroblast growth factor signalling in the hair growth cycle: expression of the fibroblast growth factor receptor and ligand genes in the murine hair follicle. Dev Dyn. 1996;205(4):379–86.

    CAS  PubMed  Google Scholar 

  59. Kishimoto J, Burgeson RE, Morgan BA. Wnt signaling maintains the hair-inducing activity of the dermal papilla. Genes Dev. 2000;14(10):1181–5.

    CAS  PubMed  PubMed Central  Google Scholar 

  60. 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 

  61. Rendl M, Polak L, Fuchs E. BMP signaling in dermal papilla cells is required for their hair follicle-inductive properties. Genes Dev. 2008;22(4):543–57.

    CAS  PubMed  PubMed Central  Google Scholar 

  62. 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.

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Randall VA, Sundberg JP, Philpott MP. Animal and in vitro models for the study of hair follicles. J Investig Dermatol Symp Proc. 2003;8(1):39–45.

    PubMed  Google Scholar 

  64. Midorikawa T, Chikazawa T, Yoshino T, Takada K, Arase S. Different gene expression profile observed in dermal papilla cells related to androgenic alopecia by DNA macroarray analysis. J Dermatol Sci. 2004;36(1):25–32.

    CAS  PubMed  Google Scholar 

  65. Rutberg SE, Kolpak ML, Gourley JA, Tan G, Henry JP, Shander D. Differences in expression of specific biomarkers distinguish human beard from scalp dermal papilla cells. J Invest Dermatol. 2006;126(12):2583–95.

    CAS  PubMed  Google Scholar 

  66. Egger A, Tomic-Canic M, Tosti A. Advances in stem cell-based therapy for hair loss. CellR4 Repair Replace Regen Reprogram. 2020;8:e2894. Epub 2020 Sep 2.

    PubMed  PubMed Central  Google Scholar 

  67. Chang CL, Sung PH, Chen KH, et al. Adipose-derived mesenchymal stem cell-derived exosomes alleviate overwhelming systemic inflammatory reaction and organ damage and improve outcome in rat sepsis syndrome. Am J Transl Res. 2018;10(4):1053–70.

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Zuk PA, Zhu M, Ashjian P, De Ugarte DA, Huang JI, Mizuno H, Alfonso ZC, Fraser JK, Benhaim P, Hedrick MH. Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell. 2002;13(12):4279–95.

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Mizuno H, Tobita M, Uysal AC. Concise review: adipose-derived stem cells as a novel tool for future regenerative medicine. Stem Cells. 2012;30(5):804–10.

    CAS  PubMed  Google Scholar 

  70. Cai L, Johnstone BH, Cook TG, Liang Z, Traktuev D, Cornetta K, Ingram DA, Rosen ED, March KL. Suppression of hepatocyte growth factor production impairs the ability of adipose-derived stem cells to promote ischemic tissue revascularization. Stem Cells. 2007;25(12):3234–43.

    CAS  PubMed  Google Scholar 

  71. Gnecchi M, He H, Liang OD, Melo LG, Morello F, Mu H, Noiseux N, Zhang L, Pratt RE, Ingwall JS, Dzau VJ. Paracrine action accounts for marked protection of ischemic heart by Akt-modified mesenchymal stem cells. Nat Med. 2005;11(4):367–8.

    CAS  PubMed  Google Scholar 

  72. Kinnaird T, Stabile E, Burnett MS, Lee CW, Barr S, Fuchs S, Epstein SE. Marrow-derived stromal cells express genes encoding a broad spectrum of arteriogenic cytokines and promote in vitro and in vivo arteriogenesis through paracrine mechanisms. Circ Res. 2004;94(5):678–85.

    CAS  PubMed  Google Scholar 

  73. Maguire G. Stem cell therapy without the cells. Commun Integr Biol. 2013;6(6):e26631.

    PubMed  PubMed Central  Google Scholar 

  74. Beer L, Mildner M, Ankersmit HJ. Cell secretome based drug substances in regenerative medicine: when regulatory affairs meet basic science. Ann Transl Med. 2017;5(7):170.

    PubMed  PubMed Central  Google Scholar 

  75. Talavera-Adame D, Newman D, Newman N. Conventional and novel stem cell based therapies for androgenic alopecia. Stem Cells Cloning. 2017;10:11–9.

    PubMed  PubMed Central  Google Scholar 

  76. Danilenko DM, Ring BD, Pierce GF. Growth factors and cytokines in hair follicle development and cycling: recent insights from animal models and the potentials for clinical therapy. Mol Med Today. 1996;2(11):460–7.

    CAS  PubMed  Google Scholar 

  77. Limat A, Hunziker T, Waelti ER, Inaebnit SP, Wiesmann U, Braathen LR. Soluble factors from human hair papilla cells and dermal fibroblasts dramatically increase the clonal growth of outer root sheath cells. Arch Dermatol Res. 1993;285(4):205–10.

    CAS  PubMed  Google Scholar 

  78. Won CH, Yoo HG, Kwon OS, Sung MY, Kang YJ, Chung JH, Park BS, Sung JH, Kim S, Kim KH. Hair growth promoting effects of adipose tissue-derived stem cells. J Dermatol Sci. 2010;57(2):134–7.

    CAS  PubMed  Google Scholar 

  79. Yuan AR, Bian Q, Gao JQ. Current advances in stem cell-based therapies for hair regeneration. Eur J Pharmacol. 2020;881:173197.

    CAS  PubMed  Google Scholar 

  80. Won CH, Park GH, Wu X, Tran TN, Park KY, Park BS, Kim DY, Kwon O, Kim KH. The basic mechanism of hair growth stimulation by adipose-derived stem cells and their secretory factors. Curr Stem Cell Res Ther. 2017;12(7):535–43.

    CAS  PubMed  Google Scholar 

  81. Kim WS, Park BS, Kim HK, Park JS, Kim KJ, Choi JS, Chung SJ, Kim DD, Sung JH. Evidence supporting antioxidant action of adipose-derived stem cells: protection of human dermal fibroblasts from oxidative stress. J Dermatol Sci. 2008;49(2):133–42.

    CAS  PubMed  Google Scholar 

  82. Park BS, Jang KA, Sung JH, Park JS, Kwon YH, Kim KJ, Kim WS. Adipose-derived stem cells and their secretory factors as a promising therapy for skin aging. Dermatol Surg. 2008;34(10):1323–6.

    CAS  PubMed  Google Scholar 

  83. Park BS, Kim WS, Choi JS, Kim HK, Won JH, Ohkubo F, Fukuoka H. Hair growth stimulated by conditioned medium of adipose-derived stem cells is enhanced by hypoxia: evidence of increased growth factor secretion. Biomed Res. 2010;31(1):27–34.

    CAS  PubMed  Google Scholar 

  84. Lee RH, Kim B, Choi I, Kim H, Choi HS, Suh K, Bae YC, Jung JS. Characterization and expression analysis of mesenchymal stem cells from human bone marrow and adipose tissue. Cell Physiol Biochem. 2004;14(4-6):311–24.

    CAS  PubMed  Google Scholar 

  85. Fukuoka H, Tadayuki S, Ohkubo F. Hair regenerated therapy with growth factors in adipose-derived stem cells secreted protein. Jpn J Plast Surg. 2010;53:1095–104.

    Google Scholar 

  86. Fukuoka H, Suga H. Hair regeneration treatment using stem cell conditioned medium. Jpn J Plast Surg. 2012;55:1083–9.

    Google Scholar 

  87. Fukuoka H, Suga H, Narita K, Watanabe R, Shintani S. The latest advance in hair regeneration therapy using proteins secreted by adipose-derived stem cells. Am J Cosmet Surg. 2012;29:273–82.

    Google Scholar 

  88. Fukuoka H, Suga H. Hair regeneration treatment using adipose-derived stem cell conditioned medium: follow-up with trichograms. Eplasty. 2015;15:e10.

    PubMed  PubMed Central  Google Scholar 

  89. Shin H, Ryu HH, Kwon O, Park BS, Jo SJ. Clinical use of conditioned media of adipose tissue-derived stem cells in female pattern hair loss: a retrospective case series study. Int J Dermatol. 2015;54(6):730–5.

    PubMed  Google Scholar 

  90. Perez-Meza D, Ziering C, Sforza M, Krishnan G, Ball E, Daniels E. Hair follicle growth by stromal vascular fraction-enhanced adipose transplantation in baldness. Stem Cells Cloning. 2017;10:1–10.

    PubMed  PubMed Central  Google Scholar 

  91. Fukuoka H, Narita K, Suga H. Hair regeneration therapy: application of adipose-derived stem cells. Curr Stem Cell Res Ther. 2017;12(7):531–4.

    CAS  PubMed  PubMed Central  Google Scholar 

  92. Tsuboi R, Niiyama S, Irisawa R, Harada K, Nakazawa Y, Kishimoto J. Autologous cell-based therapy for male and female pattern hair loss using dermal sheath cup cells: a randomized placebo-controlled double-blinded dose-finding clinical study. J Am Acad Dermatol. 2020;83(1):109–16.

    CAS  PubMed  Google Scholar 

  93. Owczarczyk-Saczonek A, Krajewska-Włodarczyk M, Kruszewska A, Banasiak Ł, Placek W, Maksymowicz W, Wojtkiewicz J. Therapeutic potential of stem cells in follicle regeneration. Stem Cells Int. 2018;2018:1049641.

    PubMed  PubMed Central  Google Scholar 

  94. Gentile P, Scioli MG, Bielli A, Orlandi A, Cervelli V. Stem cells from human hair follicles: first mechanical isolation for immediate autologous clinical use in androgenetic alopecia and hair loss. Stem Cell Investig. 2017;4:58.

    PubMed  PubMed Central  Google Scholar 

  95. Gentile P, Garcovich S. Advances in regenerative stem cell therapy in androgenic alopecia and hair loss: Wnt pathway, growth-factor, and mesenchymal stem cell signaling impact analysis on cell growth and hair follicle development. Cells. 2019;8(5):466.

    CAS  PubMed  PubMed Central  Google Scholar 

  96. Alvarez X, Valenzuela M, Tuffet J. Microscopic and histologic evaluation of the Regenera® method for the treatment of androgenetic alopecia in a small number of cases. IJRSMHS. 2017;2:19–22.

    Google Scholar 

  97. Alvarez X, Valenzuela M, Tuffet J. Clinical and histological evaluation of the Regenera® method for the treatment of androgenetic alopecia. IEASRJ. 2018;3:2456–5040.

    Google Scholar 

  98. Elmaadawi IH, Mohamed BM, Ibrahim ZAS, et al. Stem cell therapy as a novel therapeutic intervention for resistant cases of alopecia areata and androgenetic alopecia. J Dermatolog Treat. 2018;29(5):431–40.

    PubMed  Google Scholar 

  99. Gentile P. Autologous cellular method using micrografts of human adipose tissue derived follicle stem cells in androgenic alopecia. Int J Mol Sci. 2019;20(14):3446.

    CAS  PubMed  PubMed Central  Google Scholar 

  100. Tak YJ, Lee SY, Cho AR, Kim YS. A randomized, double-blind, vehicle-controlled clinical study of hair regeneration using adipose-derived stem cell constituent extract in androgenetic alopecia. Stem Cells Transl Med. 2020;9(8):839–49.

    CAS  PubMed  PubMed Central  Google Scholar 

  101. Narita K, Fukuoka H, Sekiyama T, Suga H, Harii K. Sequential scalp assessment in hair regeneration therapy using an adipose-derived stem cell-conditioned medium. Dermatol Surg. 2020;46(6):819–25.

    CAS  PubMed  Google Scholar 

  102. Lee YI, Kim J, Kim J, Park S, Lee JH. The effect of conditioned media from human adipocyte-derived mesenchymal stem cells on androgenetic alopecia after nonablative fractional laser treatment. Dermatol Surg. 2020;46(12):1698–704.

    CAS  PubMed  Google Scholar 

  103. https://clinicaltrials.gov/ct2/show/NCT01673789.

  104. https://clinicaltrials.gov/ct2/show/NCT02865421.

  105. https://clinicaltrials.gov/ct2/show/NCT03078686.

  106. https://clinicaltrials.gov/ct2/show/NCT02849470.

  107. https://clinicaltrials.gov/ct2/show/NCT03676400.

  108. https://clinicaltrials.gov/ct2/show/NCT01501617.

  109. Balañá ME, Charreau HE, Leirós GJ. Epidermal stem cells and skin tissue engineering in hair follicle regeneration. World J Stem Cells. 2015;7(4):711–27.

    PubMed  PubMed Central  Google Scholar 

  110. Abaci HE, Coffman A, Doucet Y, Chen J, Jacków J, Wang E, Guo Z, Shin JU, Jahoda CA, Christiano AM. Tissue engineering of human hair follicles using a biomimetic developmental approach. Nat Commun. 2018;9(1):5301.

    CAS  PubMed  PubMed Central  Google Scholar 

  111. Lee LF, Jiang TX, Garner W, Chuong CM. A simplified procedure to reconstitute hair-producing skin. Tissue Eng Part C Methods. 2011;17(4):391–400.

    PubMed  PubMed Central  Google Scholar 

  112. Asakawa K, Toyoshima KE, Ishibashi N, Tobe H, Iwadate A, Kanayama T, Hasegawa T, Nakao K, Toki H, Noguchi S, Ogawa M, Sato A, Tsuji T. Hair organ regeneration via the bioengineered hair follicular unit transplantation. Sci Rep. 2012;2:424.

    PubMed  PubMed Central  Google Scholar 

  113. Toyoshima KE, Asakawa K, Ishibashi N, Toki H, Ogawa M, Hasegawa T, Irié T, Tachikawa T, Sato A, Takeda A, Tsuji T. Fully functional hair follicle regeneration through the rearrangement of stem cells and their niches. Nat Commun. 2012;3:784.

    PubMed  Google Scholar 

  114. Nakao K, Morita R, Saji Y, Ishida K, Tomita Y, Ogawa M, Saitoh M, Tomooka Y, Tsuji T. The development of a bioengineered organ germ method. Nat Methods. 2007;4(3):227–30.

    CAS  PubMed  Google Scholar 

  115. Qiao J, Turetsky A, Kemp P, Teumer J. Hair morphogenesis in vitro: formation of hair structures suitable for implantation. Regen Med. 2008;3(5):683–92.

    PubMed  Google Scholar 

  116. Fan Z, Miao Y, Qu Q, Xiao S, Wang J, Du L, Liu B, Hu Z. Unlocking the vital role of host cells in hair follicle reconstruction by semi-permeable capsules. PLoS One. 2017;12(6):e0179279.

    PubMed  PubMed Central  Google Scholar 

  117. Tan Y, JJ, Kang L. Engineering the future of hair follicle regeneration and delivery. Ther Deliv. 2018;9(5):321–4.

    CAS  Google Scholar 

  118. Cotsarelis G, Sun TT, Lavker RM. Label-retaining cells reside in the bulge area of pilosebaceous unit: implications for follicular stem cells, hair cycle, and skin carcinogenesis. Cell. 1990;61(7):1329–37.

    CAS  PubMed  Google Scholar 

  119. Oshima H, Rochat A, Kedzia C, Kobayashi K, Barrandon Y. Morphogenesis and renewal of hair follicles from adult multipotent stem cells. Cell. 2001;104(2):233–45.

    CAS  PubMed  Google Scholar 

  120. Tumbar T, Guasch G, Greco V, Blanpain C, Lowry WE, Rendl M, Fuchs E. Defining the epithelial stem cell niche in skin. Science. 2004;303(5656):359–63.

    CAS  PubMed  Google Scholar 

  121. Stenn KS, et al. Future directions: bioengineering the hair follicle. In: Trüeb Ralph M, Desmond T, editors. Aging hair. 1st ed. Berlin: Springer; 2010. p. 239–48.

    Google Scholar 

  122. Jahoda CA, Oliver RF, Reynolds AJ, Forrester JC, Horne KA. Human hair follicle regeneration following amputation and grafting into the nude mouse. J Invest Dermatol. 1996;107(6):804–7.

    CAS  PubMed  Google Scholar 

  123. Pisansarakit P, Moore GP. Induction of hair follicles in mouse skin by rat vibrissa dermal papillae. J Embryol Exp Morphol. 1986;94:113–9.

    CAS  PubMed  Google Scholar 

  124. Ferraris C, Bernard BA, Dhouailly D. Adult epidermal keratinocytes are endowed with pilosebaceous forming abilities. Int J Dev Biol. 1997;41(3):491–8.

    CAS  PubMed  Google Scholar 

  125. Jahoda CA, Oliver RF. Vibrissa dermal papilla cell aggregative behaviour in vivo and in vitro. J Embryol Exp Morphol. 1984;79:211–24.

    CAS  PubMed  Google Scholar 

  126. Triel C, Vestergaard ME, Bolund L, Jensen TG, Jensen UB. Side population cells in human and mouse epidermis lack stem cell characteristics. Exp Cell Res. 2004;295(1):79–90. Erratum in: Exp Cell Res. 2007 Nov 1;313(18):3943.

    CAS  PubMed  Google Scholar 

  127. Rochat A, Kobayashi K, Barrandon Y. Location of stem cells of human hair follicles by clonal analysis. Cell. 1994;76(6):1063–73.

    CAS  PubMed  Google Scholar 

  128. Roh C, Tao Q, Photopoulos C, Lyle S. In vitro differences between keratinocyte stem cells and transit-amplifying cells of the human hair follicle. J Invest Dermatol. 2005;125(6):1099–105.

    CAS  PubMed  Google Scholar 

  129. Matsuzaki T, Inamatsu M, Yoshizato K. The upper dermal sheath has a potential to regenerate the hair in the rat follicular epidermis. Differentiation. 1996;60(5):287–97.

    CAS  PubMed  Google Scholar 

  130. Paus R, Eichmüller S, Hofmann U, Czarnetzki BM, Robinson P. Expression of classical and non-classical MHC class I antigens in murine hair follicles. Br J Dermatol. 1994;131(2):177–83.

    CAS  PubMed  Google Scholar 

  131. Inoue K, Aoi N, Yamauchi Y, et al. TGF-beta is specifically expressed in human dermal papilla cells and modulates hair folliculogenesis. J Cell Mol Med. 2009;13(11–12):4643–56.

    CAS  PubMed  PubMed Central  Google Scholar 

  132. Jahoda CA. Cell movement in the hair follicle dermis—more than a two-way street? J Invest Dermatol. 2003;121(6):ix–xi.

    CAS  PubMed  Google Scholar 

  133. Yamao M, Inamatsu M, Ogawa Y, Toki H, Okada T, Toyoshima KE, Yoshizato K. Contact between dermal papilla cells and dermal sheath cells enhances the ability of DPCs to induce hair growth. J Invest Dermatol. 2010;130(12):2707–18.

    CAS  PubMed  Google Scholar 

  134. Kwack MH, Yang JM, Won GH, Kim MK, Kim JC, Sung YK. Establishment and characterization of five immortalized human scalp dermal papilla cell lines. Biochem Biophys Res Commun. 2018;496(2):346–51.

    CAS  PubMed  Google Scholar 

  135. Lin CM, Li Y, Ji YC, Huang K, Cai XN, Li GQ. Induction of hair follicle regeneration in rat ear by microencapsulated human hair dermal papilla cells. Chin J Traumatol. 2009;12(1):49–54.

    PubMed  Google Scholar 

  136. Perez-Losada J, Balmain A. Stem-cell hierarchy in skin cancer. Nat Rev Cancer. 2003;3(6):434–43.

    CAS  PubMed  Google Scholar 

  137. Stenbäck F. Adnexal participation in formation of cutaneous tumors following topical application of 9,10-dimethyl-benzanthracene. J Cutan Pathol. 1980;7(5):277–94.

    PubMed  Google Scholar 

  138. Morris RJ, Fischer SM, Slaga TJ. Evidence that a slowly cycling subpopulation of adult murine epidermal cells retains carcinogen. Cancer Res. 1986;46(6):3061–6.

    CAS  PubMed  Google Scholar 

  139. Morris RJ. Keratinocyte stem cells: targets for cutaneous carcinogens. J Clin Invest. 2000;106(1):3–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  140. Hutchin ME, Kariapper MS, Grachtchouk M, et al. Sustained Hedgehog signaling is required for basal cell carcinoma proliferation and survival: conditional skin tumorigenesis recapitulates the hair growth cycle. Genes Dev. 2005;19(2):214–23.

    CAS  PubMed  PubMed Central  Google Scholar 

  141. Verhaegh ME, Arends JW, Majoie IM, Hoekzema R, Neumann HA. Transforming growth factor-beta and bcl-2 distribution patterns distinguish trichoepithelioma from basal cell carcinoma. Dermatol Surg. 1997;23(8):695–700.

    CAS  PubMed  Google Scholar 

  142. Stenn KS, Lawrence L, Veis D, Korsmeyer S, Seiberg M. Expression of the bcl-2 protooncogene in the cycling adult mouse hair follicle. J Invest Dermatol. 1994;103(1):107–11.

    CAS  PubMed  Google Scholar 

  143. Oro AE, Higgins KM, Hu Z, Bonifas JM, Epstein EH Jr, Scott MP. Basal cell carcinomas in mice overexpressing sonic hedgehog. Science. 1997;276(5313):817–21.

    CAS  PubMed  Google Scholar 

  144. Adolphe C, Narang M, Ellis T, Wicking C, Kaur P, Wainwright B. An in vivo comparative study of sonic, desert and Indian hedgehog reveals that hedgehog pathway activity regulates epidermal stem cell homeostasis. Development. 2004;131(20):5009–19.

    CAS  PubMed  Google Scholar 

  145. Headington JT. Tumors of the hair follicle. A review. Am J Pathol. 1976 Nov;85(2):479–514.

    CAS  PubMed  PubMed Central  Google Scholar 

  146. Gailani MR, Ståhle-Bäckdahl M, Leffell DJ, Glynn M, Zaphiropoulos PG, Pressman C, Undén AB, Dean M, Brash DE, Bale AE, Toftgård R. The role of the human homologue of Drosophila patched in sporadic basal cell carcinomas. Nat Genet. 1996;14(1):78–81.

    CAS  PubMed  Google Scholar 

  147. Johnson RL, Rothman AL, Xie J, Goodrich LV, Bare JW, Bonifas JM, Quinn G, Myers RM, Cox DR, Epstein EH Jr, Scott MP. Human homolog of patched, a candidate gene for the basal cell nevus syndrome. Science. 1996;272(5268):1668–71.

    CAS  PubMed  Google Scholar 

  148. Lee LF, Chuong CM. Building complex tissues: high-throughput screening for molecules required in hair engineering. J Invest Dermatol. 2009;129(4):815–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  149. Adenuga P, Summers P, Bergfeld W. Hair regrowth in a male patient with extensive androgenetic alopecia on estrogen therapy. J Am Acad Dermatol. 2012;67(3):e121–3.

    PubMed  Google Scholar 

  150. https://www.fda.gov/consumers/consumer-updates/fda-warns-about-stem-cell-therapies.

  151. https://www.engage.hoganlovells.com/knowledgeservices/news/times-up-new-enforcement-era-for-regenerative-medicines-begins-june-1.

  152. Marks PW, Hahn S. Identifying the risks of unproven regenerative medicine therapies. JAMA. 2020;324(3):241–2.

    PubMed  Google Scholar 

  153. https://www.fda.gov/news-events/fda-voices/advancing-development-safe-and-effective-regenerative-medicine-products.

  154. Castro AR, Logarinho E. Tissue engineering strategies for human hair follicle regeneration: how far from a hairy goal? Stem Cells Transl Med. 2020;9(3):342–50.

    PubMed  Google Scholar 

  155. Han C, Sun X, Liu L, Jiang H, Shen Y, Xu X, Li J, Zhang G, Huang J, Lin Z, Xiong N, Wang T. Exosomes and their therapeutic potentials of stem cells. Stem Cells Int. 2016;2016:7653489.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Anastassakis Hair Clinic, Athens, Attiki, Greece

    Konstantinos Anastassakis

Authors
  1. Konstantinos Anastassakis
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

Copyright information

© 2023 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Anastassakis, K. (2023). Stem Cells and Hair Follicle Cloning/Engineering. In: Androgenetic Alopecia From A to Z. Springer, Cham. https://doi.org/10.1007/978-3-031-10613-2_40

Download citation

  • DOI: https://doi.org/10.1007/978-3-031-10613-2_40

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-031-10612-5

  • Online ISBN: 978-3-031-10613-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation