The story of melanocyte: a long way from bench to bedside.

Skin is composed of major layers, namely a superficial epidermis and a deeper dermis. The color of skin is influenced by a number of pigments, including melanin, which is produced by cells called melanocytes. Most skin disorders are relatively benign, but a few, including melanomas, can be fatal. A number of more noticeable disorders, namely albinism and vitiligo, affect the appearance of the skin and its accessory organs. Vitiligo is associated with significant psycho-social morbidity and a major effect on quality of life. Topical steroids, calcineurin inhibitors, phototherapy and surgery are the most common treatments for melanoma. However, there are many patients who do not respond to any of these modalities. The transplantation of cultured or non-cultured melanocyte is the most important treatment for hypopigmentory disorders. This study aims at reviewing the history of melanocyte cultivation, and evaluating the effectiveness of transplantation of cultured cells. For this purpose, the authors examined the initial process of isolation, characterization, and transplantation of epidermal cells. This review, thus, summarizes the current understanding of the cutaneous pigmentary system from the start of synthesis in the pigment cells, along with the response of repigmentation. During the production of melanin, melanosomes are transferred to neighboring keratinocyte in order to form perinuclear melanin caps. The objective of this review is to analyze the melanocytes transplantation in the last century to date, and explore the methods epidermal cells can increase pigmentation in hypo-pigmented areas in skin disorders. Moreover, the focus is on the story of the melanocyte back to 1950s. In addition, prior systemic therapy was associated with a significant increase, based on combined additional therapy, achieving desired results and improved outcomes. Despite the short study of a long way of melanocyte assessment and following up patient treatment, results of the all reports confirmed the efficacy of the method used in the treatment of stable vitiligo patients, who did not respond to the common algorithms of non-invasive treatments.

Safety and Efficacy of Autologous Melanocyte/Keratinocyte Transplantation in Patients with Refractory Stable Vitiligo.

BACKGROUND: Vitiligo is a common depigmentation skin disease associated with significant psychosocial morbidity and profound effect on the quality of life. The treatment of vitiligo is still a major challenge in the field of dermatology. Currently, topical steroids, calcineurin inhibitors, ultraviolet phototherapy, surgery, and cultured and non-cultured epidermal melanocyte transplantation are used for the treatment of vitiligo. However, the effectiveness of these treatment modalities is limited by the lack of response, long-term treatment periods, high cost, and inevitable adverse effects. OBJECTIVES: In this study, we aimed to evaluate the efficacy of intraepidermal injection of autologous non-cultured melanocytes and keratinocytes as an alternative therapy for the refractory and stable (RS) vitiligo. METHODS: The treatment procedure was performed on thirty-nine RS vitiligo patients. The autologous skin grafts obtained from the buttock area and epidermis were separated from dermis using dispase. Single-cell autologous melanocytes and keratinocytes were prepared from the epidermis by trypsin/ethylene diamine tetra acetic acid and injected at the concentration of 100-400 × 103 cells/cm2, intra-epidermally to the selected vitiligo lesions. Vitiligo re-pigmentation was monitored employing photography. Photographs were taken prior to and 2, 4, and 6 months after the cell transplantation. Improvement of the skin depigmentation was classified as follows: <25% as minimal response, 26-50% as moderate response, 51-75% as good response, and finally 76-100% as excellent response. RESULTS: Cell infusion appeared to be safe as none of the patients exhibited any adverse effects. At the end of the sixth month follow-up period, of the treated patients, 12.8% demonstrated an excellent response, 36% exhibited a good response, and 51.2% showed a moderate to minimal response to the administered therapy. Obtained significant p value for Wilcoxon test over the checkpoints at 2nd, 4th, and 6th month (p = 0.03, 0.04, and 0.039, respectively) post-cell transplantation confirmed notable growing trend in the re-pigmentation. CONCLUSION: Our findings provide a strong support for the therapeutic efficacy of autologous non-cultured melanocytes and keratinocytes in patients with RS vitiligo.

A single-arm open-label clinical trial of autologous epidermal cell transplantation for stable vitiligo: A 30-month follow-up.

BACKGROUND: Recently, we introduced intralesional injection of autologous epidermal cells as a safe and feasible approach for transplantation in patients with stable vitiligo. This approach resulted in less pain during and after the procedure, no scarring or cobblestone formation at the recipient site, and was more feasible to perform on curved surfaces such as joints, lips, eyelids, ears, and face. OBJECTIVE: In this study, we aimed to investigate the long-term efficacy and safety of this transplantation technique. METHODS: In this open-label and single-arm clinical trial, we enrolled 300 patients with stable vitiligo. We obtained a partial thickness normo-pigmented skin specimen from the patients' thigh-buttock junction with an area of one tenth to one third of the recipient site area. The epidermal cell suspension was prepared by processing the autologous skin specimen. We injected the cell suspension into 1060 vitiligo patches in 300 patients. Patients did not use any adjuvant phototherapy during the study. An experienced dermatologist and patients respectively defined the repigmentation score and self-assessment score at regular follow-up visits for up to 30 months after treatment. The scores represented the repigmentation percentage as follows: 0 (0), I (1%-24%), II (25%-49%), III (50%-74%), and IV (75%-100%). RESULTS: The mean repigmentation score at 3 months post-transplantation was 1.12±0.73. A significant upward trend existed in the mean repigmentation score until 9 months after cell transplantation, when the mean repigmentation score reached to 1.98±1.20. At 9 months after treatment, repigmentation of >50% was obtained in 32.2% of treated patches. Acquired repigmentation remained stable in 79.3% of treated patches during the follow-up period. The number of received cells per cm2 positively influenced the repigmentation score. Patches located on face, neck and trunk showed significantly higher response to the treatment. CONCLUSION: The results of our study demonstrated efficacy and safety of autologus epidermal cell transplantation on repigmentation of vitiligo patches. The achieved repigmentation was stable in the majority of treated patches during the follow-up period.