Advanced Therapy Medicinal Products in Vitiligo; Current Status, Future Prospect, and Approved Treatments

Document Type : Review Article


Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran


Vitiligo is an auto-immune disease, causing depigmentation of skin in 0.2-1.8% of global population. Topical
corticosteroids and calcineurin inhibitors are the only treatments with firm evidence of optimal effectiveness with
considerable side effects. Phototherapies might not induce serious side effects, although the effectiveness of the method
is limited. Advanced therapy medicinal products (ATMPs) are emerging treatment modalities based on correction and
replacement of affected genes, damaged tissues or cells in treatment of difficult-to-treat diseases. Due to optimal
effectiveness and minimal side effects, ATMPs have recently gained much attention in order to develop new treatments.
In this review, the ATMPs for treating vitiligo were along with its clinical success, affordability and cost-effectiveness.
Currently, the main ATMP based products using in treatment of vitiligo are non-cultured epidermal cell, melanocytes,
and hair follicle melanocytes. These products have shown promising results in the non-responding vitiligo patients.
Furthermore, mesenchymal stem cells and multi-lineage differentiating stress enduring cells are other new potential
modalities. Recently, Iranian Food and Drug Administration (IR-FDA) authorized the first cell-based product for vitiligo.
This product is autologous suspension of keratinocytes and melanocytes. Although ATMPs are efficient and could be
cost-effective in long term, the most important obstacle is affordability of them. This could be facilitated by insurance
companies and instalments payment programs from manufacturers.


Main Subjects

  1. Zhang Y, Cai Y, Shi M, Jiang S, Cui S, Wu Y, et al. The prevalence of vitiligo: a meta-analysis. PLoS One. 2016; 11(9): e0163806.
  2. Kubelis-López DE, Zapata-Salazar NA, Said-Fernández SL, Sánchez-Domínguez CN, Salinas-Santander MA, Martínez-Rodríguez HG, et al. Updates and new medical treatments for vitiligo (Review). Exp Ther Med. 2021; 22(2): 797.
  3. Morrison B, Burden-Teh E, Batchelor JM, Mead E, Grindlay D, Ratib S. Quality of life in people with vitiligo: a systematic review and meta- analysis. Br J Dermatol. 2017; 177(6): e338-e339.
  4. Van TN, Minh TT, Huu DL, Huu SN, Thanh TV, Huu ND, et al. Successful treatment of vitiligo vietnamese patients with Vitilinex® herbal bio-actives in combination with phototherapy. Open Access Maced J Med Sci. 2019; 7(2): 283-286.
  5. Karagaiah P, Schwartz RA, Lotti T, Wollina U, Grabbe S, Goldust M. Biologic and targeted therapeutics in vitiligo. J Cosmet Dermatol. 2023; 22(1): 64-73.
  6. Karagaiah P, Valle Y, Sigova J, Zerbinati N, Vojvodic P, Parsad D, et al. Emerging drugs for the treatment of vitiligo. Expert Opin Emerg Drugs. 2020; 25(1): 7-24.
  7. Ramírez-Marín HA, Tosti A. Evaluating the therapeutic potential of ritlecitinib for the treatment of alopecia areata. Drug Des Devel Ther. 2022; 16: 363-374.
  8. Kadry M, Tawfik A, Abdallah N, Badawi A, Shokeir H. Platelet-rich plasma versus combined fractional carbon dioxide laser with platelet- rich plasma in the treatment of vitiligo: a comparative study. Clin Cosmet Investig Dermatol. 2018; 11: 551-559.
  9. Chen J, Yu N, Li H, Tang Y, Zhu H. Meta-analysis of the efficacy of adding platelet-rich plasma to 308-nm excimer laser for patients with vitiligo. J Int Med Res. 2022; 50(9): 3000605221119646.
  10. Saberi S, Karamzadeh R, Moghadam P, Kadivari M, Eghbal Behbahani B, Heydari Z, et al. Research performance in stem cell science and regenerative medicine in iran: a national comprehensive observation. Arch Iran Med. 2019; 22(6): 318-327.
  11. Chang HC, Hsu YP, Huang YC. The effectiveness of topical calcineurin inhibitors compared with topical corticosteroids in the treatment of vitiligo: a systematic review and meta-analysis. J Am Acad Dermatol. 2020; 82(1): 243-245.
  12. Bae JM, Jung HM, Hong BY, Lee JH, Choi WJ, Lee JH, et al. Phototherapy for vitiligo: a systematic review and meta-analysis. JAMA Dermatol. 2017; 153(7): 666-674.
  13. Hossein-Khannazer N, Torabi S, Hosseinzadeh R, Shahrokh S, Asadzadeh Aghdaei H, Memarnejadian A, et al. Novel cell-based therapies in inflammatory bowel diseases: the established concept, promising results. Hum Cell. 2021; 34(5): 1289-1300.
  14. Lloyd-Williams H, Hughes DA. A systematic review of economic evaluations of advanced therapy medicinal products. Br J Clin Pharmacol. 2021; 87(6): 2428-2443.
  15. Takaya K, Kato T, Ishii T, Sakai S, Okabe K, Aramaki-Hattori N, et al. Clinical analysis of cultured epidermal autograft (JACE) transplantation for giant congenital melanocytic nevus. Plast Reconstr Surg Glob Open. 2021; 9(1): e3380.
  16. Matsumura H, Matsushima A, Ueyama M, Kumagai N. Application of the cultured epidermal autograft “JACE(®”) for treatment of severe burns: results of a 6-year multicenter surveillance in Japan. Burns. 2016; 42(4): 769-776.
  17. Spritz RA, Santorico SA. The genetic basis of vitiligo. J Invest Dermatol. 2021; 141(2): 265-273.
  18. Rashighi M, Harris JE. Vitiligo pathogenesis and emerging treatments. Dermatol Clin. 2017; 35(2): 257-265.
  19. Seleit I, Bakry OA, Abdou AG, Dawoud NM. Immunohistochemical study of melanocyte-melanocyte stem cell lineage in vitiligo; a clue to interfollicular melanocyte stem cell reservoir. Ultrastruct Pathol. 2014; 38(3): 186-198.
  20. El-Zawahry BM, Esmat S, Bassiouny D, Zaki NS, Sobhi R, Saleh MA, et al. Effect of procedural-related variables on melanocytekeratinocyte suspension transplantation in nonsegmental stable vitiligo: a clinical and immunocytochemical study. Dermatol Surg. 2017; 43(2): 226-235.
  21. 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(5): 785-793.
  22. Bertolotti A, Leone G, Taïeb A, Soriano E, Pascal M, Maillard H, et al. Assessment of non-cultured autologous epidermal cell grafting resuspended in hyaluronic acid for repigmenting vitiligo and piebaldism lesions: a randomized clinical trial. Acta Derm Venereol. 2021; 101(7): adv00506.
  23. 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(8): 593-599.
  24. Subburaj K, Thakur V, Kumaran MS, Vinay K, Srivastava N, Parsad D. A prospective, randomized clinical study to compare the efficacy of recipient site preparation using dermabrasion, cryoblister, and dermaroller in autologous noncultured epidermal cell suspension in stable vitiligo. Dermatol Ther. 2021; 34(1): e14683.
  25. 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(5): 1293-1298.
  26. Thakur V, Kumar S, Kumaran MS, Kaushik H, Srivastava N, Parsad D. Efficacy of transplantation of combination of noncultured dermal and epidermal cell suspension vs epidermal cell suspension alone in vitiligo: a randomized clinical trial. JAMA Dermatol. 2019; 155(2): 204-210.
  27. Zhu L, Lin X, Zhi L, Fang Y, Lin K, Li K, et al. Mesenchymal stem cells promote human melanocytes proliferation and resistance to apoptosis through PTEN pathway in vitiligo. Stem Cell Res Ther. 2020; 11(1): 26.
  28. Chang WL, Lee WR, Kuo YC, Huang YH. Vitiligo: an autoimmune skin disease and its immunomodulatory therapeutic intervention. Front Cell Dev Biol. 2021; 9: 797026.
  29. Klar AS, Biedermann T, Michalak K, Michalczyk T, Meuli-Simmen C, Scherberich A, et al. Human adipose mesenchymal cells inhibit melanocyte differentiation and the pigmentation of human skin via increased expression of TGF-β1. J Invest Dermatol. 2017; 137(12): 2560-2569.
  30. Paino F, Ricci G, De Rosa A, D’Aquino R, Laino L, Pirozzi G, et al. Ecto-mesenchymal stem cells from dental pulp are committed to differentiate into active melanocytes. Eur Cell Mater. 2010; 20: 295-305.
  31. Jones JC, Sabatini K, Liao X, Tran HT, Lynch CL, Morey RE, et al. Melanocytes derived from transgene-free human induced pluripotent stem cells. J Invest Dermatol. 2013; 133(8): 2104-2108.
  32. Mull AN, Zolekar A, Wang YC. Understanding melanocyte stem cells for disease modeling and regenerative medicine applications. Int J Mol Sci. 2015; 16(12): 30458-30469.
  33. Razmi TM, Afra TP, Parsad D. Vitiligo surgery: a journey from tissues via cells to the stems! Exp Dermatol. 2019; 28(6): 690-694.
  34. Saleh AA, Salam OHA, Metwally GH, Abdelsalam HA, Hassan MA, Sosa WS. Comparison treatment of vitiligo by co-culture of melanocytes derived from hair follicle with adipose-derived stem cells with and without NB-UVB. Pigmentary Disorders. 2017; 4(256): 1-8.
  35. Hampson G, Towse A, Pearson SD, Dreitlein WB, Henshall C. Gene therapy: evidence, value and affordability in the US health care system. J Comp Eff Res. 2018; 7(1): 15-28.