Adipose-Derived Stem Cells Improve Efficacy of Melanocyte Transplantation in Animal Skin

Abstract

Vitiligo is a pigmentary disorder induced by a loss of melanocytes. In addition to replacement of pure melanocytes, cocultures of melanocytes with keratinocytes have been used to improve the repigmentation outcome in vitiligo treatment. We previously identified by in vitro studies, that adipose-derived stem cells (ADSCs) could be a potential substitute for keratinocytes in cocultures with melanocytes. In this study, the efficacy of pigmentation including durability of grafted melanocytes and short-term safety was examined in the nude mouse and Sprague-Dawley rat after grafting of primary cultured human melanocytes, with or without different ratios of primary cultured human ADSCs. Simultaneous grafting of melanocytes and ADSCs, which were separately cultured and mixed on grafting at the ratios of 1:1, 1:2, or 1:3, showed better efficacy than that of pure melanocytes. Grafting of melanocytes cocultured with ADSCs resulted in a similar outcome as the grafting of cell mixtures. Skin pigmentation by melanocytes : ADSCs at the ratios of 1:1 and 1:2 was better than at 1:3. No significant difference was observed between the 1-week and 2-week durations in coculturing. Time-course microscopic examination showed that the grafted melanocytes remained a little longer than 6-week post-grafting. No inflammatory cell infiltration was observed in the grafted skin and no melanocytes were detectable in other organs. Collectively, grafting of melanocytes and ADSCs was equally safe and more effective than grafting of melanocytes alone. Despite the absence of significant differences in efficacy between the group of 1:1 and that of 1:2 ratio, 1:2 ratio for 1-week coculturing may be better for clinical use from the cost-benefit viewpoint.

Comparison Treatment of Vitiligo by Co-culture of Melanocytes Derived from Hair Follicle with Adipose-Derived Stem Cells with and without NB-UVB

“…Unfortunately this study hasn't been done before on human but similar study was done on skin animals, in a study made by Lim et al [20] on lab animals showed that, Grafting of melanocytes co cultured with ADSCs increased melanocyte number in nude mice compared to melanocyte monocultures.…”

The Use of Adipose-Derived Stem Cells in Selected Skin Diseases (Vitiligo, Alopecia, and Nonhealing Wounds)

“…Repigmentation of vitiligo depends on available melanocytes from three possible sources: from the hair follicle unit which is the main provider of pigment cells, from the border of vitiligo lesions, and from unaffected melanocytes within depigmented areas [ 32 ]. Melanocytes rarely undergo mitosis without growth factors; therefore, mitogenic factors are used in transplantation treatments for this disease [ 33 , 34 ]. Repigmentation occurs due to the migration of melanocyte stem cells (MelSCs) located in the lower part of the hair follicle (infundibulum).…”

“…Repigmentation occurs due to the migration of melanocyte stem cells (MelSCs) located in the lower part of the hair follicle (infundibulum). Therefore, this process starts perifolliculary [ 33 – 36 ].…”

The importance and use of stem cells in dermatology

“…Pigmentacja zaczyna pojawiać się pomiędzy 4. a 5. tygodniem i trwa do 6 miesięcy, a nawet dłużej [32]. Ponieważ melanocyty rzadko podlegają mitozie bez pomocy czynników wzrostu lub czynników mitogennych, efekty podawania samych melanocytów w plamy bielacze były słabsze niż w przypadku podawania ich z komórkami naskórka w formie przeszczepów [34,35].…”

“…Stwierdzono lepsze efekty jednoczesnego podawania melanocytów i ADSCs, które hoduje się oddzielnie i miesza się w proporcji 1 : 1, 1 : 2 lub 1 : 3 w porównaniu z podawaniem tylko czystych melanocytów [34].…”