Lenalidomide Augments Differentiation of Cultured Hair Follicle Derived Melanocyte Stem Cells Into Functional Melanocytes
Keywords:
Lenalidomide, Melanocyte stem cells, Melanocytes, differentiationAbstract
Introducion: Melanocyte progenitors are embryonically derived from the neural crest and subsequently get localized in hair follicles and epidermis to provide hair and skin pigmentation. These progenitor cells in hair follicles repeatedly proliferate and differentiate to maintain pigmentation. Vitiligo, a pigmentary disorder, is associated with loss of melanocytes. Repigmentation of vitiligo lesions mainly depends upon the proliferation, migration and differentiation of melanocyte stem cells (MelSCs) into functional melanocytes. Current study is designed to check the efficacy of lenalidomide, an imide drug in the differentiation of MelSCs into functional melanocytes.
Objectives: Aim of the study is to check the effect of lenalidomide in the proliferation, migration of cultured hair follicle derived melanocyte stem cells and their differentiation into functional melanocytes.
Methods: Primary culture of MelSCs was established from whisker hair of C57BL/6 mice. Proliferation and migration of cultured cells were done by MTT assay and boyden’s chamber migration assay, respectively. Effect of lenalidomide on the MelSCs differentiation was checked at gene level by qPCR & protein expression was checked by immunocytochemistry.
Results: A significant increase in the migration of MelSCs in comparison to control was also observed. Lenalidomide treatment significantly increased the expression of melanocyte specific genes in cultured MelSCs as compared to control.
Conclusion: From the results we concluded that lenalidomide induce the proliferation and migration of MelSCs and accelerate the differentiation of MelSCs into functional melanocytes.
References
Nishimura EK. Melanocyte stem cells: a melanocyte reservoir in hair follicles for hair and skin pigmentation. Pigment Cell Melanoma Res. 2011;24(3):401-410. doi.org/10.1111/j.1755-148X.2011.00855.x.
Li H, Fan L, Zhu S, et al. Epilation induces hair and skin pigmentation through an EDN3/EDNRB-dependent regenerative response of melanocyte stem cells. Sci. Rep. 2017;7(1):1-13. doi.org/10.1038/s41598-017-07683-x.
Falabella R. Vitiligo and the melanocyte reservoir. Indian J. Dermatol. 2009;54:313-318. doi: 10.4103/0019-5154.57604
Bellono NW, Oancea EV. Ion transport in pigmentation. Arch Biochem. 2014;563:35-41. doi.org/10.1016/j.abb.2014.06.020.
Nordlund JJ. The pigmentary system and inflammation. Pigment Cell Res. 1992;5(5):362-365. doi.org/10.1111/j.1600-0749.1992.tb00563.x.
Lai YC, Yew YW, Kennedy C, et al. Vitiligo and depression: A systematic review and meta-analysis of observational studies. Br. J. Dermatol 2017;177(3):708–718. doi.org/10.1111/bjd.15199.
Lotti TM, Berti SF, Hercogova J, et al. Vitiligo: Recent insights and new therapeutic approaches. GiornaleItaliano di Dermatologia e Venereologia: OrganoUfficiale, SocietaItaliana di Dermatologia e Sifilografia, 2012;147(6):637–647.
Goldstein NB, Koster MI, Hoaglin LG, et al. Narrow band ultraviolet B treatment for human vitiligo is associated with proliferation, migration, and differentiation of melanocyte precursors. J Invest Dermatol. 2015;135:2068–2076. doi.org/10.1038/jid.2015.126.
Milrod CJ, Blevins F, Hughes D, et al. Incidence of skin hyperpigmentation in Black patients receiving treatment with immunomodulatory drugs. Blood 2021;137(21):2987–2989. doi.org/10.1182/blood.2021010853.
Dasanu CA, Mitsis D, Alexandrescu DT. Hair repigmentation associated with the use of lenalidomide: graying may not be an irreversible process. J Oncol Pharma Pract. 20119(2):165-169. doi.org/10.1177/1078155212442561.
Pervaiz N, Kaur H, Parsad D, et al. Immune‐modulatory effects of lenalidomide inhibited the progression of lesions in a vitiligo mouse model. Pigment Cell Melanoma Res. 2021;34(5):918-927. doi.org/10.1111/pcmr.12962.
Gilanchi S, Esmaeilzade B, Eidi A, et al. Neuronal differentiation of rat hair follicle stem cells: the involvement of the neuroprotective factor Seladin-1 (DHCR24). Iran Biomed J. 2014;18(3):136. doi.org/10.6091/ibj.1284.2014.
Li L, Fukunaga-Kalabis M, Yu H, et al. Human dermal stem cells differentiate into functional epidermal melanocytes. J Cell Sci. 2010;123(6):853-860. doi.org/10.1242/jcs.061598.
Osada A, Iwabuchi T, Kishimoto J, et al. Long-term culture of mouse vibrissal dermal papilla cells and de novo hair follicle induction. J Tissue Eng. 2007;13(5):975-982. doi.org/10.1089/ten.2006.0304.
Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983;65(1-2):55-63. doi.org/10.1016/0022-1759(83)90303-4.
Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2− ΔΔCT method. Methods. 2001;25(4):402-408. doi.org/10.1006/meth.2001.1262.
Ortonne JP, Schmitt D, Thivolet J. PUVA-induced repigmentation of vitiligo: scanning electron microscopy of hair follicles. J Invest Dermatol. 1980;74:40–42. doi.org/10.1006/meth.2001.1262.
Buffoli B, Rinaldi F, Labanca M, et al. The human hair: from anatomy to physiology. Int J Dermatol. 2014;53:331–341. doi.org/10.1111/ijd.12362.
Zeuner MT, Didenko NN, Humphries D, et al. Isolation and characterization of neural crest-derived stem cells from adult ovine palatal tissue. Front. Cell Dev. Biol. 2018;6:39. doi.org/10.3389/fcell.2018.00039.
Amoh Y, Li L, Yang M, et al. Nascent blood vessels in the skin arise from nestin-expressing hair follicle cells. Proc Natl Acad Sci USA. 2004;101:13291-5. doi.org/10.1073/pnas.0405250101.
Li L, Mignone J, Yang M, Matic et al. Nestin expression in hair follicle sheath progenitor cells. Proc. Natl. Acad. Sci. USA. 2003;100:9958–9961. doi.org/10.1073/pnas.1733025100.
Osawa M, Egawa G, Mak SS, et al. Molecular characterization of melanocyte stem cells in their niche. Development. 2005;132(24):5589–5599. doi.org/10.1242/dev.02161.
Joshi SS, Tandukar B, Pan L, et al. CD34 defines melanocyte stem cell subpopulations with distinct regenerative properties. PLoS Genet. 2019;15(4):1008034. doi.org/10.1371/journal.pgen.1008034.
Colombo S, Berlin I, Delmas V, et al. Classical and nonclassical melanocytes in vertebrates (pp. 21-61). Weinheim, Germany: Wiley-Blackwell. 2011
Qiu W, Yang K, Lei M, et al. SCF/c-kit signaling is required in 12-O-tetradecanoylphorbol-13-acetate-induced migration and differentiation of hair follicle melanocytes for epidermal pigmentation. Cell Tissue Res. 2015;360(2):333-346. doi.org/10.1007/s00441-014-2101-8.
Cui J, Shen LY, Wang GC. Role of hair follicles in the repigmentation of vitiligo. J Invest Dermatol. 1991;97(3):410-416. doi.org/10.1111/1523-1747.ep12480997.
Verhelle D, Corral LG, Wong K, et al. Lenalidomide and CC-4047 inhibit the proliferation of malignant B cells while expanding normal CD34+ progenitor cells. Cancer Res. 2007;67(2):746-755. Doi. 10.1158/0008-5472.CAN-06-2317.
Kawakami A, Fisher DE. The master role of microphthalmia-associated transcription factor in melanocyte and melanoma biology. Lab Invest. 2017;97(6):649-656. doi: 10.1038/labinvest.2017.9.
Wu M, Chen X, Cui K, et al. Pigmentation formation and expression analysis of tyrosinase in Sinipercachuatsi. Fish Physiol Biochem. 2020;46(4):1279-1293. doi: 10.1007/s10695-020-00788-7.
Wegner M. Secrets to a healthy Sox life: lessons for melanocytes. Pigment Cell Res. 2005;18:74–85. doi: 10.1111/j.1600-0749.2005.00218.x.
Yasumoto KI, Yokoyama K, Shibata K, et al. Microphthalmia-associated transcription factor as a regulator for melanocyte specific transcription of the human tyrosinase gene. Mol. Cell. Biol. 1994;14(12):8058-8070. doi.10.1128/mcb.14.12.8058-8070.1994.
Bertolotto C, Abbe P, Bille K, et al. Different cis-acting elements are involved in the regulation of TRP1 and TRP2promoter activities bycyclic AMP: pivotal role of M boxes (GTCATGTGCT)and of microphthalmia. Mol. Cell. Biol. 1998;18(2):694-702. doi: 10.1128/MCB.18.2.694.
Published
Issue
Section
License
Copyright (c) 2023 Uma Kumari, Naveed Pervaiz, Harjot Kaur, Himani Sharma, Davinder Parsad, Ravinder Kumar
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Dermatology Practical & Conceptual applies a Creative Commons Attribution License (CCAL) to all works we publish (http://creativecommons.org/licenses/by-nc/4.0/). Authors retain the copyright for their published work.
How to Cite
Share
