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H. Aoki, T. Kunisada; Regenerative Pigmentation of Adult Iris by the Transplantation of Melanocytes From Es Cells and Melanocytes Derived From Neonatal Mice or Human Epidermis and Adult Mice Uvea. Invest. Ophthalmol. Vis. Sci. 2008;49(13):5771.
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© ARVO (1962-2015); The Authors (2016-present)
A culture system to generate melanocytes from undifferentiated mouse embryonic stem (ES) cells has been established. The melanocytes generated require the same growth and/or transcription factors such as c-kit/SCF, endothelin 3 and Mitf, as in vivo melanocyte development. The aim of this study is to investigate the potential of these ES cell-derived melanocytes to populate when transplanted into adult developed tissue.
Mouse ES cells were induced to differentiate into melanocytes in vitro for 19 days on ST2 stromal cells. Neonatal mice skin and adult mice uvea processed by trypsin and dispase and human melanocyte cell line were prepared as donor cells containing melanocytes for comparison. They were transplanted onto the iris. Eyes were analyzed by histology and immunohistochemistry 10 or more days after transplantation
In the iris, transplanted ES cell-derived melanocytes were efficiently integrated without any teratogenetic features. ES cell-derived melanocytes showed the characteristic dendritic morphology and pigment granules as comparable with the melanocytes from mouse neonatal epidermis at 10 days after transplantation. Moreover, transplanted melanocytes from ES cells as well as neonatal epidermis were observed at 20 or 30 days after transplantation. ES cell-drived melanocytes extended through the iris from transplanted area toward the opposite site and facilitated the pigmentation of the iris. Also, in the transplantation of melanocytes from neonatal epidermis, most of the iris was uniformly pigmented. Melanocytes from adult mice uvea also integrated into the host iris. Most of the transplanted blackly pigmented cells had the melanocyte-specific dendritic morphology. However, some of them were not dendritic, but round in shape as IPE. Human melanocytes were found on the iris as heavily pigmented cells with dendritic morphology.
Several origins of melanocytes including ES cells were thus shown to survive, differentiate and proliferate on the iris of an allogenic host in spite of the fact that the albino host mice contained unpigmented but differentiated melanocytes in their irides. Our results suggested that melanocytes derived from ES cells in our culture systems were comparable to in vivo counterparts. The efficient integration of the pigmented melanocytes into the iris is a very important first step for the future cell therapy directed to the large number of the people who suffer from heterochromia iridia and photophobia.
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