Hair Follicle as a Source of Pigment-Producing Cells for Treatment of Vitiligo: An Alternative to Epidermis?

Mahshid Ghasemi, Amir Bajouri, Saeed Shafiiyan, Nasser Aghdami, Mahshid Ghasemi, Amir Bajouri, Saeed Shafiiyan, Nasser Aghdami

Abstract

To discuss the advantages and limitations of hair follicle-derived cell transplantation (FCT) in vitiligo, compared to the epidermal cell transplantation (ECT), and the knowledge gap which is required to be bridged. The papers relevant to the purpose was reviewed. Surgical approaches for treating vitiligo are based on the idea of replenishing lost melanocytes. Skin and hair follicles as the main sources of melanocytes have been applied for this purpose transferring the whole tissue or tissue-derived cell suspension to the vitiligo lesions. Considering the differences between hair follicle and epidermis in terms of the constituting cell populations, phenotype and function of melanocytes, and micro-environmental factors, different response of vitiligo patients to treatment with FCT or ECT would be expected theoretically. However, there is currently a lack of evidence on such a difference. However, ECT appears to be a more feasible, less time-consuming, and more comfortable treatment for both physicians and patients. Although the current evidence has not shown a significant difference between ECT and FCT in terms of efficacy, ECT appears to be more feasible specifically in the treatment of large lesions. However, further randomized controlled clinical trials with larger sample sizes and longer follow-up durations are required to be conducted to draw a definite conclusion on comparing FCT with ECT in terms of the safety, efficacy, durability of the therapeutic effects, and indications in vitiligo patients.

Keywords: Cell therapy; Hair follicle; Melanocyte; Regenerative medicine; Vitiligo.

Conflict of interest statement

The authors declare that there is no conflict of interest.

References

    1. Rusfianti M, Wirohadidjodjo YW. Dermatosurgical techniques for repigmentation of vitiligo. Int J Dermatol. 2006;45:411–417.
    1. Khunger N, Kathuria SD, Ramesh V. Tissue grafts in vitiligo surgery-past, present, and future. Indian J Dermatol. 2009;54:150–158.
    1. Olsson MJ, Juhlin L. Leucoderma treated by transplantation of a basal cell layer enriched suspension. Br J Dermatol. 1998;138:644–648.
    1. van Geel N, Ongenae K, De Mil M, Naeyaert JM. Modified technique of autologous noncultured epidermal cell transplantation for repigmenting vitiligo: a pilot study. Dermatol Surg. 2001;27:873–876.
    1. Olsson M, Juhlin L. Long-term follow-up of leucoderma patients treated with transplants of autologous cultured melanocytes, ultrathin epidermal sheets and basal cell layer suspension. Br J Dermatol. 2002;147:893–904.
    1. van Geel N, Ongenae K, De Mil M, Vander Haeghen Y, Vervaet C, Naeyaert JM. Double-blind placebo-controlled study of autologous transplanted epidermal cell suspensions for repigmenting vitiligo. Arch Dermatol. 2004;140:1203–1208.
    1. Khodadadi L, Shafieyan S, Sotoudeh M, Dizaj AV, Shahverdi A, Aghdami N, et al. Intraepidermal injection of dissociated epidermal cell suspension improves vitiligo. Arch Dermatol Res. 2010;302:593–599.
    1. van Geel N, Wallaeys E, Goh BK, De Mil M, Lambert J. Long-term results of noncultured epidermal cellular grafting in vitiligo, halo naevi, piebaldism and naevus depigmentosus. Br J Dermatol. 2010;163:1186–1193.
    1. Toossi P, Shahidi-Dadras M, Mahmoudi Rad M, Fesharaki RJ. Non-cultured melanocyte-keratinocyte transplantation for the treatment of vitiligo: a clinical trial in an Iranian population. J Eur Acad Dermatol Venereol. 2011;25:1182–1186.
    1. Huggins RH, Henderson MD, Mulekar SV, Ozog DM, Kerr HA, Jabobsen G, et al. Melanocyte-keratinocyte transplantation procedure in the treatment of vitiligo: the experience of an academic medical center in the United States. J Am Acad Dermatol. 2012;66:785–793.
    1. Lerner AB, Halaban R, Klaus SN, Moellmann GE. Transplantation of human melanocytes. J Invest Dermatol. 1987;89:219–224.
    1. Pianigiani E, Risulo M, Andreassi A, Taddeucci P, Ierardi F, Andreassi L. Autologous epidermal cultures and narrow-band ultraviolet B in the surgical treatment of vitiligo. Dermatol Surg. 2005;31:155–159.
    1. Redondo P, del Olmo J, García-Guzman M, Guembe L, Prósper F. Repigmentation of vitiligo by transplantation of autologous melanocyte cells cultured on amniotic membrane. Br J Dermatol. 2008;158:1168–1171.
    1. Yao L, Zhong SX, Hu DN, Guo JW, Li SS, Xie XL, et al. Repigmentation of leukotrichia in vitiligo with transplantation of cultured autologous melanocytes. Int J Dermatol. 2014;53:1016–1018.
    1. Czajkowski R, Placek W, Drewa T, Kowaliszyn B, Sir J, Weiss W. Autologous cultured melanocytes in vitiligo treatment. Dermatol Surg. 2007;33:1027–1036.
    1. Fioramonti P, Onesti MG, Marchese C, Carella S, Ceccarelli S, Scuderi N. Autologous cultured melanocytes in vitiligo treatment comparison of two techniques to prepare the recipient site: erbium-doped yttrium aluminum garnet laser versus dermabrasion. Dermatol Surg. 2012;38:809–812.
    1. Fu LF, Zhang DM, Xu AE. De-epithelialization of vitiliginous area for transplantation of cultured autologous melanocyte: a case report of two patients with different methods. Int J Dermatol. 2012;51:747–749.
    1. Cui J, Shen LY, Wang GC. Role of hair follicles in the repigmentation of vitiligo. J Invest Dermatol. 1991;97:410–416.
    1. Arrunátegui A, Arroyo C, Garcia L, Covelli C, Escobar C, Carrascal E, et al. Melanocyte reservoir in vitiligo. Int J Dermatol. 1994;33:484–487.
    1. Ortonne JP, MacDonald DM, Micoudz A, Thivolet J. PUVA-induced repigmentation of vitiligo: a histochemical (split-DOPA) and ultrastructural study. Br J Dermatol. 1979;101:1–12.
    1. Ortonne JP, Schmitt D, Thivolet J. PUVA-induced repigmentation of vitiligo: scanning electron microscopy of hair follicles. J Invest Dermatol. 1980;74:40–42.
    1. Buffoli B, Rinaldi F, Labanca M, Sorbellini E, Trink A, Guanziroli E, et al. The human hair: from anatomy to physiology. Int J Dermatol. 2014;53:331–341.
    1. Na GY, Seo SK, Choi SK. Single hair grafting for the treatment of vitiligo. J Am Acad Dermatol. 1998;38:580–584.
    1. Aziz Jalali M, Jafari B, Isfahani M, Nilforoushzadeh MA. Treatment of segmental vitiligo with normal-hair follicle autograft. Med J Islam Repub Iran. 2013;27:210–214.
    1. Malakar S, Dhar S. Repigmentation of vitiligo patches by transplantation of hair follicles. Int J Dermatol. 1999;38:237–238.
    1. Sardi JR. Surgical treatment for vitiligo through hair follicle grafting: how to make it easy. Dermatol Surg. 2001;27:685–686.
    1. Kumaresan M. Single-hair follicular unit transplant for stable vitiligo. J Cutan Aesthet Surg. 2011;4:41–43.
    1. Chouhan K, Kumar A, Kanwar AJ. Body hair transplantation in vitiligo. J Cutan Aesthet Surg. 2013;6:111–112.
    1. Vanscheidt W, Hunziker T. Repigmentation by outer-root-sheath-derived melanocytes: proof of concept in vitiligo and leucoderma. Dermatology. 2009;218:342–343.
    1. Tobin DJ, Bystryn JC. Different populations of melanocytes are present in hair follicles and epidermis. Pigment Cell Res. 1996;9:304–310.
    1. Tobin DJ, Colen SR, Bystryn JC. Isolation and long-term culture of human hair-follicle melanocytes. J Invest Dermatol. 1995;104:86–89.
    1. Slominski A, Wortsman J, Plonka PM, Schallreuter KU, Paus R, Tobin DJ. Hair follicle pigmentation. J Invest Dermatol. 2005;124:13–21.
    1. Tobin DJ, Paus R. Graying: gerontobiology of the hair follicle pigmentary unit. Exp Gerontol. 2001;36:29–54.
    1. Gho CG, Braun JE, Tilli CM, Neumann HA, Ramaekers FC. Human follicular stem cells: their presence in plucked hair and follicular cell culture. Br J Dermatol. 2004;150:860–868.
    1. Chou WC, Takeo M, Rabbani P, Hu H, Lee W, Chung YR, et al. Direct migration of follicular melanocyte stem cells to the epidermis after wounding or UVB irradiation is dependent on Mc1r signaling. Nat Med. 2013;19:924–929.
    1. Kwon H, Liu PH, Lew DH, Nishimura E, Orgill DP. Hair follicle melanocyte cells as a renewable source of melanocytes for culture and transplantation. Eplasty. 2008;8:e7.
    1. Na GY, Paek SH, Park BC, Kim DW, Lee WJ, Lee SJ, et al. Isolation and characterization of outer root sheath melanocytes of human hair follicles. Br J Dermatol. 2006;155:902–909.
    1. Staricco RG, Miller-Milinska A. Activation of the amelanotic melanocytes in the outer root sheath of the hair follicle following ultra violet rays exposure. J Invest Dermatol. 1962;39:163–164.
    1. Lin SJ, Chuong CM. Toward the isolation and culture of melanocyte stem cells. J Invest Dermatol. 2011;131:2341–2343.
    1. Lee BW, Schwartz RA, Hercogová J, Valle Y, Lotti TM. Vitiligo road map. Dermatol Ther. 2012;25:S44–S56.
    1. Tobin DJ. The cell biology of human hair follicle pigmentation. Pigment Cell Melanoma Res. 2011;24:75–88.
    1. Singh C, Parsad D, Kanwar AJ, Dogra S, Kumar R. Comparison between autologous noncultured extracted hair follicle outer root sheath cell suspension and autologous noncultured epidermal cell suspension in the treatment of stable vitiligo: a randomized study. Br J Dermatol. 2013;169:287–293.
    1. El-Zawahry BM, Esmat S, Bassiouny D, Zaki NS, Sobhi R, Saleh MA, et al. Effect of procedural-related variables on melanocyte-keratinocyte suspension transplantation in nonsegmental stable vitiligo: a clinical and immunocytochemical study. Dermatol Surg. 2017;43:226–235.
    1. Donaparthi N, Chopra A. Comparative study of efficacy of epidermal melanocyte transfer versus hair follicular melanocyte transfer in stable vitiligo. Indian J Dermatol. 2016;61:640–644.
    1. Orouji Z, Bajouri A, Ghasemi M, Mohammadi P, Fallah N, Shahbazi A, et al. A single-arm open-label clinical trial of autologous epidermal cell transplantation for stable vitiligo: a 30-month follow-up. J Dermatol Sci. 2017;89:52–59.
    1. Pincelli C, Marconi A. Keratinocyte stem cells: friends and foes. J Cell Physiol. 2010;225:310–315.
    1. Potten CS, Booth C. Keratinocyte stem cells: a commentary. J Invest Dermatol. 2002;119:888–899.
    1. Ohyama M, Terunuma A, Tock CL, Radonovich MF, Pise-Masison CA, Hopping SB, et al. Characterization and isolation of stem cell–enriched human hair follicle bulge cells. J Clin Invest. 2006;116:249–260.
    1. Ohyama M. Hair follicle bulge: a fascinating reservoir of epithelial stem cells. J Dermatol Sci. 2007;46:81–89.
    1. Hirobe T. Keratinocytes regulate the function of melanocytes. Dermatol Sin. 2014;32:200–204.
    1. Sellheyer K, Krahl D. Skin mesenchymal stem cells: prospects for clinical dermatology. J Am Acad Dermatol. 2010;63:859–865.
    1. Mohanty S, Kumar A, Dhawan J, Sreenivas V, Gupta S. Noncultured extracted hair follicle outer root sheath cell suspension for transplantation in vitiligo. Br J Dermatol. 2011;164:1241–1246.
    1. Zhou MN, Zhang ZQ, Wu JL, Lin FQ, Fu LF, Wang SQ, et al. Dermal mesenchymal stem cells (DMSCs) inhibit skin-homing CD8 + T cell activity, a determining factor of vitiligo patients’ autologous melanocytes transplantation efficiency. PLoS One. 2013;8:e60254.
    1. Kaur P, Li A, Redvers R, Bertoncello I. Keratinocyte stem cell assays: an evolving science. J Invest Dermatol Symp. 2004;9:238–247.
    1. Li L, Fukunaga-Kalabis M, Yu H, Xu X, Kong J, Lee JT, et al. Human dermal stem cells differentiate into functional epidermal melanocytes. J Cell Sci. 2010;123:853–860.
    1. Kumar A, Mohanty S, Sahni K, Kumar R, Gupta S. Extracted hair follicle outer root sheath cell suspension for pigment cell restoration in vitiligo. J Cutan Aesthet Surg. 2013;6:121–125.
    1. Poswal A. The preshaving protocol in body hair-to-scalp transplant to identify hair in anagen phase. Indian J Dermatol. 2010;55:50–52.
    1. Dua A, Dua K. Follicular unit extraction hair transplant. J Cutan Aesthet Surg. 2010;3:76–81.
    1. Vinay K, Dogra S, Parsad D, Kanwar AJ, Kumar R, Minz RW, et al. Clinical and treatment characteristics determining therapeutic outcome in patients undergoing autologous non-cultured outer root sheath hair follicle cell suspension for treatment of stable vitiligo. J Eur Acad Dermatol Venereol. 2015;29:31–37.
    1. Kumar A, Gupta S, Mohanty S, Bhargava B, Airan B. Stem cell niche is partially lost during follicular plucking: a preliminary pilot study. Int J Trichology. 2013;5:97–100.
    1. Harris JA. New methodology and instrumentation for follicular unit extraction: lower follicle transection rates and expanded patient candidacy. Dermatol Surg. 2006;32:56–61.
    1. Shah AN, Marfatia RK, Saikia SS. A study of noncultured extracted hair follicle outer root sheath cell suspension for transplantation in vitiligo. Int J Trichology. 2016;8:67–72.
    1. Dieckmann C, Milkova L, Hunziker T, Emmendörffer A, Simon JC. Human melanocytes can be isolated, propagated and expanded from plucked anagen hair follicles. Exp Dermatol. 2010;19:543–545.
    1. Lommerts JE, Meesters AA, Komen L, Bekkenk MW, de Rie MA, Luiten RM, et al. Autologous cell suspension grafting in segmental vitiligo and piebaldism: a randomized controlled trial comparing full surface and fractional CO2 laser recipient-site preparations. Br J Dermatol. 2017;177:1293–1298.
    1. Parambath N, Sharma VK, Parihar AS, Sahni K, Gupta S. Use of platelet-rich plasma to suspend noncultured epidermal cell suspension improves repigmentation after autologous transplantation in stable vitiligo: a double-blind randomized controlled trial. Int J Dermatol. 2019;58:472–476.
    1. Redondo P, Giménez de Azcarate A, Marqués L, García-Guzman M, Andreu E, Prósper F. Amniotic membrane as a scaffold for melanocyte transplantation in patients with stable vitiligo. Dermatol Res Pract. 2011;2011:532139.
    1. Sverdlov ED, Mineev K. Mutation rate in stem cells: an underestimated barrier on the way to therapy. Trends Mol Med. 2013;19:273–280.
    1. Zhu WY, Zhang RZ, Ma HJ, Wang DG. Isolation and culture of amelanotic melanocytes from human hair follicles. Pigment Cell Res. 2004;17:668–673.
    1. Ma HJ, Yue XZ, Wang DG, Li CR, Zhu WY. A modified method for purifying amelanotic melanocytes from human hair follicles. J Dermatol. 2006;33:239–248.
    1. Savkovic V, Dieckmann C, Milkova L, Simon JC. Improved method of differentiation, selection and amplification of human melanocytes from the hair follicle cell pool. Exp Dermatol. 2012;21:948–950.
    1. Wang D, Xu X, Ma H, Yue X, Li C, Zhu W. Optimization of the method for the culture of melanocyte precursors from hair follicles and their activation by 1, 25-dihydroxyvitamin D3. Exp Ther Med. 2013;6:967–972.
    1. Gauthier Y, Surleve-Bazeille JE. Autologous grafting with noncultured melanocytes: a simplified method for treatment of depigmented lesions. J Am Acad Dermatol. 1992;26:191–194.
    1. Silpa-Archa N, Griffith JL, Williams MS, Lim HW, Hamzavi IH. Prospective comparison of recipient-site preparation with fractional carbon dioxide laser vs. dermabrasion and recipient-site dressing composition in melanocyte–keratinocyte transplantation procedure in vitiligo: a preliminary study. Br J Dermatol. 2016;174:895–897.
    1. Al-Hadidi N, Griffith JL, Al-Jamal MS, Hamzavi I. Role of recipient-site preparation techniques and post-operative wound dressing in the surgical management of vitiligo. J Cutan Aesthet Surg. 2015;8:79– 87.
    1. Nahhas AF, Mohammad TF, Hamzavi IH, editors. Vitiligo surgery: shuffling melanocytes. J Investig Dermatol Symp Proc. 2017;18:S34–7.
    1. Vázquez-Martínez OT, Matínez-Rodríguez HG, Velásquez-Arenas L, Baños-González D, Ortíz-López R, Padilla-Rivas G, et al. Treatment of vitiligo with a melanocytes-keratiocyte cell suspension versus dermabrasion only: a pilot study with a 12 month follow up. J Drugs Dermatol. 2011;10:1032–1036.
    1. Awad SS. Dermabrasion may repigment vitiligo through stimulation of melanocyte precursors and elimination of hyperkeratosis. J Cosmet Dermatol. 2012;11:318–322.
    1. Bayoumi W, Fontas E, Sillard L, Le Duff F, Ortonne JP, Bahadoran P, et al. Effect of a preceding laser dermabrasion on the outcome of combined therapy with narrowband ultraviolet B and potent topical steroids for treating nonsegmental vitiligo in resistant localizations. Br J Dermatol. 2012;166:208–211.
    1. Razmi M, Parsad D, Kumaran SM. Combined epidermal and follicular cell suspension as a novel surgical approach for acral vitiligo. J Am Acad Dermatol. 2017;76:564–567.
    1. Cervelli V, De Angelis B, Balzani A, Colicchia G, Spallone D, Grimaldi M. Treatment of stable vitiligo by ReCell system. Acta Dermatovenerol Croat. 2009;17:273–8.
    1. Ebadi A, Rad MM, Nazari S, Fesharaki RJ, Ghalamkarpour F, Younespour S. The additive effect of excimer laser on non-cultured melanocyte–keratinocyte transplantation for the treatment of vitiligo: a clinical trial in an Iranian population. J Eur Acad Dermatol Venereol. 2015;29:745–751.

Source: PubMed

Patrocinadores e Colaboradores

Condições médicas

Intervenções de drogas

3
Se inscrever