Stem Cell Research & Therapy
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It is a model of ancient Greek neoplatonism, which is believed to reproduce the same pattern at every stage of the universe. In this system, the center is human of the universe.
Vitiligo
Coculture with adipose-derived stem cells (ADSCs) can stimulate proliferation and migration of melanocytes. To enhance out- comes of skin disorders caused by melanocyte loss or death, mixed transplantation with ADSCs has been suggested.
ACKNOWLEDGMENTS
This study was supported by the National Research Foun- dation of Korea (NRF) grant funded by the Korean Govern- ment (MSIT) (No.NRF-2017R1A2A2A09069507 and NRF- 2018R1A5A2023127)
Original ArticleBiomol Ther 27(2), November 9, 2020
Pathogenesis of vitiligo
Vitiligo is an autoimmune disease in which CD8+ T-cells target and destroy melanocytes, leaving areas of skin without pigment production. Nonsegmental vitiligo, the classical form of the disease, results in symmetrical, bilateral white patches. Vitiligo is a chronic, unpredictable disease, characterized by flares, with depigmentation and periods of disease arrest alternating. This process can be stressful and negatively impact one’s quality of life. Various hypotheses have been offered, including cellular stress causing degeneration of melanocytes, chemical toxicity causing melanocyte death, and neural changes that influence melanocytes or their ability to produce melanin. Recently, the interaction between oxidative stress and autoimmune-mediated melanocyte loss has been proposed as the primary pathogenesis of vitiligo. It is now well accepted that interferon-γ and/or C-X-C motif chemokine ligand 10 axis is functionally required for both progression and maintenance of vitiligo, making this pathway a potential therapeutic target. Most therapeutic interventions in the management of vitiligo have been developed based on this immunopathogenesis. This article aims to review the current understanding of the vitiligo pathogenesis.
Original ArticleBiomol Ther 27(2), 185-192 (2019)
Adipose-Derived Stem Cell Coculturing Stimulates Integrin-Mediated Extracellular Matrix Adhesion of Melanocytes by Upregulating Growth Factors
Coculture with adipose-derived stem cells (ADSCs) can stimulate proliferation and migration of melanocytes. To enhance out- comes of skin disorders caused by melanocyte loss or death, mixed transplantation with ADSCs has been suggested. However, role of cocultured ADSCs in proliferation and migration of melanocytes remains unclear. This study determined the effect of ADSCs on production of growth factors and expression levels of intergrins in primary culture of adult human melanocytes with or without ADSCs and in nude mice grafted with such melanocytes. Higher amounts of growth factors for melanocytes, such as bFGF and SCF were produced and released from ADSCs by coculturing with melanocytes. Relative levels of integrins β1, α5, and α6 as well as adhesion to fibronectin and laminin were increased in melanocytes cocultured with ADSCs. Such increases were inhibited by neutralization of bFGF or SCF. Relative levels of bFGF, SCF and integrins were increased in nude mice skin after grafting with melanocyte+ADSC cocultures. Collectively, these results indicate that ADSCs can stimulate proliferation and migration of melanocytes by increasing expression of integrins in melanocytes through upregulation of production/release of me- lanocyte growth factors such as bFGF and SCF.
Original Article
Biomol Ther 22(4), 328-333 (2014)
Adipose-Derived Stem Cells Improve Efficacy of Melanocyte Transplantation in Animal Skin
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 iden- tifi ed 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 effi cacy 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 differ- ent 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 effi cacy than that of pure melanocytes. Grafting of melano- cytes 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 signifi cant 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 infl ammatory cell infi ltration 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 signifi cant differences in effi cacy 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-benefi t viewpoint.Key Words: Melanocytes, Adipose-derived stem cells, Grafting, Animal, Effi cacy, Short-term safety
Acta Derm Venereol
2012; 92: 16–23
Acta Derm Venereol
2012; 92: 16–23
Acta Derm Venereol
2012; 92: 16–23
Co-culture of Melanocytes with Adipose-derived Stem Cells as a Potential Substitute for Co-culture with Keratinocytes
Cell-to-cell interactions between melanocytes and kerati- nocytes increase the proliferation and migration of mela- nocytes. In fact, mixed keratinocyte and melanocyte cul- tures have been used for autologous cell transplantation for treatment of vitiligo. However, this may require taking an amount of skin tissue large enough to leave scars. In this study, the in vitro effect of adipose-derived stem cells (ADSCs) on proliferation, differentiation and migration of melanocytes was compared with that of keratinocytes using immunohistochemistry and a Boyden chamber migration assay. The proliferation and migration of melanocytes was significantly stimulated by co-culture with ADSCs compared with melanocyte monocultures, although the effect of ADSCs was less powerful than that of keratinocytes. This may be related to increases in stem cellfactorandbasicfibroblastgrowthfactor,growthfac- tors for melanocytes, produced by the ADSCs. The ratios of melanocytes stained with antibodies against Trp-2, E-cadherinandN-cadherinweresignificantlyincreased by co-culturing with ADSCs compared with co-culturing with keratinocytes as well as melanocyte monocultures. The proportion of less-pigmented melanocytes was also increased and sustained for a longer duration in the pre- sence of ADSCs. Our data show that co-culturing with ADSCs results in increased melanocyte proliferation and migration while reducing differentiation, and could provide a means to treat disorders such as vitiligo. Key words: adipose-derived stem cells; keratinocytes; co-cultu- re; melanocytes; proliferation; differentiation; migration.
Core Values
Core Values
Adipose-derived Stem Cells as a Potential Substitute for Co-culture with Keratinocytes
Melanocytes by Upregulating Growth Factors
Proliferation of melanocytes by coculturing with ADSCs in our previous study (Kim et al., 2012) suggests a direct or in- direct cell-cell interaction between melanocytes and ADSCs. Melanocytes require growth factors for their proliferation (Jim-bow et al., 1975; Pawelek, 1979). bFGF and SCF are well- known growth factors for melanocytes.
Adipose-derived Stem Cells as a Potential Substitute for Co-culture with Keratinocytes
Stimulation of melanocyte proliferation by adipose-derived stem cells vs. keratinocytes Before examining the effect of feeder cells on me- lanocyte proliferation, the proliferative activity of feeder cells in the supplement-starved Medium 254 was examined. Because ADSCs, but not keratinocytes, proliferated in the Medium 254, 5 μg/ml MMC was added to the medium to reduce cell proliferation by less than half during the 3-week culture period (data not shown). A fixed number of MMC-treated ADSCs were co-cultured with different quantities of melano- cytes for 3 weeks.
Adipose-Derived Stem Cells Improve Efficacy of Melanocyte Transplantation in Animal Skin
Vitiligo results from a loss of melanocytes. Although various ways have been developed to replace melanocytes, their ef- fi cacy remains to be improved. We previously identifi ed that ADSCs could be a potential substitute for keratinocytes in co- cultures with melanocytes in vitro (Kim et al., 2012), hence we accordingly determined the in vivo effectiveness in this study.