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Stem Cell-Based Therapies for Hair Loss: What is the Evidence from a Clinical Perspective?

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Hair Follicle Regeneration

Part of the book series: Stem Cell Biology and Regenerative Medicine ((STEMCELL,volume 72))

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Abstract

Introduction: Stem cell-based therapies, especially those based on stem cell-derived conditioned medium (CM) are being widely explored in the clinical setting as a promising therapy for hair follicle regeneration. Based upon the pathogenesis of androgenetic alopecia (AGA) where the ability of hair follicle stem cells to differentiate into progenitors is disrupted, the goal of stem cell-derived CM is to restore the signals responsible for hair follicle stem cell activation. In this chapter we provide an up-to-date review of the stem cell-based technologies being used for hair regeneration, including outcomes of the clinical studies, therapeutic potential and possible mechanisms of action. Methods: For the selection of literature cited we used Pubmed database and ClinicalTrials.gov. The keywords used in the Pubmed and ClinicalTrials.gov. research were: alopecia, androgenetic alopecia; hair loss; hair growth; stem cell; stem cell therapy; platelet-rich plasma (PRP); stromal vascular fraction cells (SVFs); cell-free therapy; secretome; stem cell conditioned media (CM); mesenchymal stem cell exosomes; adipose-derived exosomes; clinical trials. Results: The use of PRP for the treatment of AGA has received considerable attention, but the lack of standard protocols (various centrifugation methods, platelet concentrations obtained, whether or not activators are added, etc.) has resulted in conflicting clinical outcomes. Several studies using SVF or stem cells show improvement in hair density in AGA patients, but need to be validated with more rigorous randomized placebo-controlled studies. Recently, many clinical studies have shown positive effects of stem cell CM on hair regeneration. Adipose stem cell derived-CM including growth factors and cytokines, enhances hair thickness and hair density, stimulates the transition to anagen, and promotes dermal papilla cell proliferation via activation of both Erk and Akt signaling pathways. Conclusion: The role of stem cell-based therapies in hair loss disorders is still in its infancy. Due to the some limitations of stem cell therapies the use of the stem cell secretome rather than stem cells themselves is emerging as a new alternative to hair loss treatment because of its efficacy in hair growth while avoiding potential risks of cell-based therapies. Overall, more randomized controlled, double-blind studies with larger sample sizes, objective evaluation methodologies and longer follow-up periods, as well as improved delivery systems are needed to evaluate and confirm the clear-cut benefits of stem cells and stem cell derived CM in the treatment of hair loss.

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Byung-Soon Park is the founder and stockholder of PROSTEMICS Co., Ltd. Hye-In Choi is an employee of PROSTEMICS Co., Ltd.

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References

  1. Garza LA, Yang C, Zhao T, Blatt HB, Lee M, He H et al (2011) 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 121(2):613–622

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Pantelireis N, Higgins CA (2018) A bald statement—current approaches to manipulate miniaturisation focus only on promoting hair growth. Exp Dermatol 27(9):959–965

    Article  PubMed  Google Scholar 

  3. 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 (2012) Hair organ regeneration via the bioengineered hair follicular unit transplantation. Sci Rep 2:424

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. Balañá ME, Charreau HE (2015) Leirós GJ Epidermal stem cells and skin tissue engineering in hair follicle regeneration. Word J Stem Cells 7:711–727

    Article  Google Scholar 

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

    Google Scholar 

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

    Google Scholar 

  7. Bak DH, Choi MJ, Kim SR, Lee BC, Kim JM, Jeon ES, Oh W, Lim ES, Park BC, Kim MJ, Na J, Kim BJ (2018) Human umbilical cord blood mesenchymal stem cells engineered to overexpress growth factors accelerate outcomes in hair growth. Korean J Physiol Pharmacol. 22:555–566

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Inukai T, Katagiri W, Yoshimi R, Osugi M, Kawai T, Hibi H, Ueda M (2013) Novel application of stem cell-derived factors for periodontal regeneration. Biochem Biophys Res Commun 430:763–768

    Article  CAS  PubMed  Google Scholar 

  9. Katagiri W, Osugi M, Kawai T, Ueda M (2013) Novel cell-free regeneration of bone using stem cell–derived growth factors. Int J Oral Maxillofac Implants 28:1009–1016

    Article  PubMed  Google Scholar 

  10. Bacakova L, Zarubova J, Travnickova M, Musilkova J, Pajorova J, Slepicka P, Kasalkova NS, Svorcik V, Kolska Z, Motarjemi H, Molitor M (2018) Stem cells: their source, potency and use in regenerative therapies with focus on adipose-derived stem cells–a review. Biotechnol Adv 36:1111–1126

    Article  PubMed  Google Scholar 

  11. Egger A, Tomic-Canic M, Tosti A (2020) Advances in stem cell-based therapy for hair loss. Cell R4 Repair Replace Regen Reprogram 8:e2894

    Google Scholar 

  12. Moore KA, Lemischka IR (2006) Stem cells and their niches. Science 311:1880–1885

    Article  CAS  PubMed  Google Scholar 

  13. Weissman IL (2000) Stem cells: Units of development, units of regeneration, and units in evolution. Cell 100:157–168

    Article  CAS  PubMed  Google Scholar 

  14. Gentile P, Cole JP, Cole MA, Garcovich S, Bielli A, Scioli MG, Orlandi A, Insalaco C, Cervelli V (2017a) Evaluation of not-activated and activated PRP in hair loss treatment: role of growth factor and cytokine concentrations obtained by different collection systems. Int J Mol Sci 18:1–16

    Google Scholar 

  15. Iman Hamed E, Basma Mourad M, Zeinab Abel Samad I, Said Mohamed A, Yasmina Ahmed EA, Amira Y, Maha Mostafa S, Atef T, Hala Gabr M, Mohamed MEA, Mohamed Labib S (2016) Stem cell therapy as a novel therapeutic intervention for resistant cases of alopecia areata and androgenetic alopecia. J Dermatol Treat 29:431–440

    Google Scholar 

  16. Yoo BY, Shin YH, Yoon HH, Seo YK, Song KY, Park JK (2010) Optimization of the reconstruction of dermal papilla like tissues employing umbilical cord mesenchymal stem cells. Biotechnol Bioprocess Eng 15:182–190

    Article  CAS  Google Scholar 

  17. Zanzottera F, Lavezzari E, Trovato L, Icardi A, Graziano A (2014) Adipose derived stem cells and growth factors applied on hair transplantation: follow-up of clinical outcome. J Cosmet Dermatol Sci 4:268–274

    Google Scholar 

  18. Falto-Aizpurua L, Choudhary S, Tosti A (2014) Emerging treatments in alopecia. Expert Opin Emerg Drugs 19:545–556

    Article  CAS  PubMed  Google Scholar 

  19. Richardson SM, Kalamegam G, Pushparaj PN, Matta C, Memic A, Khademhosseini A, Mobasheri R, Poletti FL, Hoyland JA, Mobasheri A (2016) Mesenchymal stem cells in regenerative medicine: Focus on articular cartilage and intervertebral disc regeneration. Methods 99:69–80

    Article  CAS  PubMed  Google Scholar 

  20. Gunawardena TNA, Rahman MT, Abdullah BJJ, Abu Kasim NH (2019) Conditioned media derived from mesenchymal stem cell cultures: the next generation for regenerative medicine. J Tissue Eng Regen Med 13(4):569–586

    Article  CAS  PubMed  Google Scholar 

  21. Badran KW, Sand JP (2018) Platelet-rich plasma for hair loss: Review of methods and results. Facial Plast Surg Clin North Am 26:469–485

    Article  PubMed  Google Scholar 

  22. Gentile P, Garcovich S (2019) 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 8:466

    Article  CAS  PubMed Central  Google Scholar 

  23. Jha AK, Udayan UK, Roy PK, Amar AKJ, Chaudhary RKP (2018) Original article: Platelet-rich plasma with microneedling in androgenetic alopecia along with dermoscopic pre- and post-treatment evaluation. J Cosmet Dermatol 17:313–318

    Article  PubMed  Google Scholar 

  24. Singh S (2015) Role of platelet-rich plasma in chronic alopecia areata: Our centre experience. Indian J Plast Surg. 48:7–59

    Google Scholar 

  25. York K, Meah N, Bhoyrul B, Sinclair R (2020) Treatment review for male pattern hair-loss. Expert Opin Pharmacother 21:603–612

    Article  CAS  PubMed  Google Scholar 

  26. Giordano S, Romeo M, Lankinen P (2017) Platelet-rich plasma for androgenetic alopecia: does it work? evidence from meta analysis. J Cosmet Dermatol 16:374–381

    Article  PubMed  Google Scholar 

  27. Stevens J, Khetarpal S (2019) Platelet-rich plasma for androgenetic alopecia: A review of the literature and proposed treatment protocol. Int J Womens Dermatol 5:46–51

    Article  CAS  PubMed  Google Scholar 

  28. Girijala RL, Riahi RR, Cohen PR, Girijala RL (2018) Platelet-rich plasma for androgenic alopecia treatment: a comprehensive review. Dermatol Online J 24:1–13

    Google Scholar 

  29. Gupta AK, Cole J, Deutsch DP et al (2019) Platelet rich plasma as treatment for androgenetic alopecia. Dermatol Surg 45:1262–1273

    Article  CAS  PubMed  Google Scholar 

  30. Oh JH, Kim W, Roh YH, Park KU (2015) Comparison of the cellular composition and cytokine-release kinetics of various platelet-rich plasma preparations. Am J Sports Med 43:3062–3070

    Article  PubMed  Google Scholar 

  31. Gawdat HI, Hegazy RA, Fawzy MM, Fathy M (2014) Autologous platelet rich plasma: topical versus intradermal after fractional ablative carbon dioxide laser treatment of atrophic acne scars. Dermatol Surg 40:152–161

    Article  CAS  PubMed  Google Scholar 

  32. Klosova H, Stetinsky J, Bryjová I, Hledík S, Klein L (2013) Objective evaluation of the effect of autologous platelet concentrate on post-operative scarring in deep burns. Burns 39:1263–1276

    Article  PubMed  Google Scholar 

  33. Motolese A, Vignati F, Antelmi A, Satumi V (2015) Effectiveness of platelet-rich plasma in healing necrobiosis lipoidica diabeticorum ulcers. Clin Exp Dermatol 40:39–41

    Article  CAS  PubMed  Google Scholar 

  34. Cervelli V, Garcovich S, Bielli A, Cervelli G, Curcio BC, Scioli MG, Orlandi A, Gentile P (2014) The effect of autologous activated platelet rich plasma (AA-PRP) injection on pattern hair loss: clinical and histomorphometric evaluation. BioMed Res Int 2014:760709

    Google Scholar 

  35. Gkini MA, Kouskoukis AE, Tripsianis G, Rigopoulos D, Kouskoukis K (2014) Study of platelet-rich plasma injections in the treatment of androgenetic alopecia through a one-year period. J Cutan Aesthet Surg 7:213–219

    Article  PubMed  PubMed Central  Google Scholar 

  36. Li ZJ, Choi HI, Choi DK, Sohn KC, Im M, Seo YJ, Lee YH, Lee JH, Lee Y (2012) Autologous platelet-rich plasma: A potential therapeutic tool for promoting hair growth. Dermatol Surg 38:1040–1046

    Article  CAS  PubMed  Google Scholar 

  37. Gentile P, Garcovich S, Scioli MG, Bielli A, Orlandi A, CervelliV (2018) Mechanical and controlled PRP injections in patients affected by androgenetic alopecia. J Vis Exp 27:131

    Google Scholar 

  38. Gentile P, Garcovich S (2020) Systematic review of platelet-rich plasma use in androgenetic alopecia compared with Minoxidil®, Finasteride®, and adult stem cell-based therapy. Int J Mol Sci 21:2702

    Google Scholar 

  39. Rodrigues B, Montalvão S, Cancela R, Silva F, Urban A, Huber S, Júnior JL, Lana JM, Annichinno-Bizzacchi JM (2019) Treatment of male pattern alopecia with platelet-rich plasma: a double-blind controlled study with analysis of platelet number and growth factor levels. J Am Acad Dermatol 80:694–700

    Article  CAS  PubMed  Google Scholar 

  40. Bourin P, Bunnell BA, Casteilla L, Dominici M, Katz AJ, March KL, Gimble JM (2013) Stromal cells from the adipose tissue-derived stromal vascular fraction and ulture expanded adipose tissue-derived stromal/stem cells: a joint statement of the International Federation for Adipose Therapeutics and Science (IFATS) and the International Society for Cellular Therapy (ISCT). Cytotherapy 15(6):641–648

    Article  PubMed  PubMed Central  Google Scholar 

  41. Cohen SR, Hewett S, Ross L, Delaunay F, Goodacre A, Ramos C, Saad A (2017) Regenerative cells for facial surgery: biofilling and biocontouring. Aesthetic Surg J 37(suppl_3):S16-S32

    Google Scholar 

  42. Festa E, Fretz J, Berry R, Schmidt B, Rodeheffer M, Horowitz M, Horsley V (2011) Adipocyte lineage cells contribute to the skin stem cell niche to drive hair cycling. Cell 146:761–771

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Lee P, Sadick NS, Diwan AH, Zhang PS, Liu JS, Prieto VG, Zhu CC, Zhu C (2005) Expression of androgen receptor coactivator ARA70/ELE1 in androgenic alopecia. J Cutan Pathol 32:567–571

    Article  PubMed  Google Scholar 

  44. Zhang P, Kling RE, Ravuri SK, Kokai LE, Rubin JP, Chai JK, Marra KG (2014) A review of adipocyte lineage cells and dermal papilla cells in hair follicle regeneration. J Tissue Eng 5:1–10

    Article  CAS  Google Scholar 

  45. Perez-Meza D, Ziering C, Sforza M, Krishna G, Ball E, Daniels E (2017) Hair follicle growth by stromal vascular fraction-enhanced adipose transplantation in baldness. Stem Cells Cloning Adv Appl:10

    Google Scholar 

  46. Sabapathy V, Sundaram B, Sreelakshmi V M, Mankuzhy P, Kumar S (2014) Human Wharton’s jelly mesenchymal stem cells plasticity augments scar-free skin wound healing with hair growth. PloS one 9:e93726

    Google Scholar 

  47. Ruiz RG, Resell JMC, Cecarelli G et al (2019) Progenitor cell-enriched micrografts as a novel option for the management of androgenetic alopecia. J Cell Physiol:1–7

    Google Scholar 

  48. Teixeira FG, Carvalho MM, Sousa N, Salgado AJ (2013) Mesenchymal stem cells secretome: a new paradigm for central nervous system regeneration? Cell Mol Life Sci 70(20):3871–3882

    Article  CAS  PubMed  Google Scholar 

  49. Gnecchi M, He H, Liang OD, Melo LG, Morello F, Mu H, Dzau VJ et al (2005) Paracrine action accounts for marked protection of ischemic heart by Akt-modified mesenchymal stem cells. Nat Med 11(4):367–368

    Article  CAS  PubMed  Google Scholar 

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

    Google Scholar 

  51. Shin H, Ryu HH, Kwon O, Park BS, Jo SJ (2015) Clinical use of conditioned media of adipose tissue-derived stem cells in female pattern hair loss: a retrospective case series study. Int J Dermatol 54:730–735

    Article  PubMed  Google Scholar 

  52. Kinnaird T, Stabile E, Burnett MS, Lee CW, Barr S, Fuchs S, Epstein SE (2004) 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 94:678–685

    Article  CAS  PubMed  Google Scholar 

  53. Kruglikov IL, Scherer PE (2016) Dermal adipocytes and hair cycling: Is spatial heterogeneity a characteristic feature of the dermal adipose tissue depot? Exp Dermato 25:258–262

    Article  CAS  Google Scholar 

  54. Pawitan JA (2014) Prospect of stem cell conditioned medium in regenerative medicine. BioMed Res Int:965849

    Google Scholar 

  55. Haque N, Rahman MT, Abu Kasim NH, Alabsi AM (2013) Hypoxic culture conditions as a solution for mesenchymal stem cell sased regenerative therapy. Sci World J:632972

    Google Scholar 

  56. Hawkins KE, Sharp TV (2013) The role of hypoxia in stem cell potency and differentiation. Regen Med 8:771–782

    Article  CAS  PubMed  Google Scholar 

  57. Vizoso FJ, Eiro N, Cid S, Schneider J, Perez-Fernandez R (2017) Mesenchymal stem cell secretome: Toward cell-free therapeutic strategies in regenerative medicine. Int J Mol Sci 18:1852

    Article  PubMed Central  CAS  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  59. Kim JH, Kim WK, Sung YK, Kwack MH, Song SY, Choi JS, Park SG, Yi T, Lee HJ, Kim DD, Seo HM, Song SU, Sung JH (2014) The molecular mechanism underlying the proliferating and preconditioning effect of vitamin C on adipose-derived stem cells. Stem Cells Dev 23:1364–1376

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Yang Y, Choi H, Seon M, Cho D, Bang SI (2016) LL-37 stimulates the functions of adipose- derived stromal/stem cells via early growth response 1 and the MAPK pathway. Stem Cell Res Ther 7:58

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  61. Won CH, Yoo HG, Kwon OS, Sung MY, Kang YJ, Chung JH, Park BS, Sung JH, Kim WS, Kim KH (2010) Hair growth promoting effects of adipose tissue-derived stem cells. J Dermatol Sci 57:134–137

    Article  CAS  PubMed  Google Scholar 

  62. Won CH, Park GH, Wu X, Tran TN, Park KY, Park BS, Kim DY, Kwon O, Kim KH (2017) The basic mechanism of hair growth stimulation by adipose-derived stem cells and their secretory factors. Curr Stem Cell Res Ther 12:535–543

    Article  CAS  PubMed  Google Scholar 

  63. Shin H, Won CH, Chung WK, Park BS (2017) Up-to-date clinical trials of hair regeneration using conditioned media of adipose-derived stem cells in male and female pattern hair loss. Curr Stem Cell Res Ther 12(7):524–530

    Article  CAS  PubMed  Google Scholar 

  64. Fukuoka H, Suga H, Narita K, Watanabe R, Shintani S (2012) The latest advance in hair regeneration therapy using proteins secreted by adipose-derived stem cells. Am J Cosmetic Surg 29(4):273–282

    Article  Google Scholar 

  65. Fukuoka H, Narita K, Suga H (2017) Hair regeneration therapy: application of adipose-derived stem cells. Curr Stem Cell Res Ther 12(7):531–534

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Narita K, Fukuoka H, Sekiyama T, Suga H, Harii K (2020) Sequential scalp assessment in hair regeneration therapy using an adipose-derived stem cell-conditioned medium. Dermatol Surg 46(6):819–825

    Article  CAS  PubMed  Google Scholar 

  67. Lee YI, Kim J, Kim J, Park S, Lee JH (2020) The effect of conditioned media from human adipocyte-derived mesenchymal stem cells on androgenetic alopecia after nonablative fractional laser treatment. Dermatol Surg 46(12):1698–1704

    Article  CAS  PubMed  Google Scholar 

  68. Oh HA, Kwak J, Kim BJ, Jin HJ, Park WS, Choi SJ, Um S et al (2020) Migration inhibitory factor in conditioned medium from human umbilical cord blood-derived mesenchymal stromal cells stimulates hair growth. Cells 9(6):1344

    Article  CAS  PubMed Central  Google Scholar 

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Byung-Soon Park is the founder and stockholder of PROSTEMICS Co., Ltd. Hye-In Choi is an employee of PROSTEMICS Co., Ltd.

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Park, BS., Choi, HI. (2022). Stem Cell-Based Therapies for Hair Loss: What is the Evidence from a Clinical Perspective?. In: Jimenez, F., Higgins, C. (eds) Hair Follicle Regeneration. Stem Cell Biology and Regenerative Medicine, vol 72. Humana, Cham. https://doi.org/10.1007/978-3-030-98331-4_10

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