HDAC Inhibitors as Epigenetic Regulators

However, further studies are needed to determine whether these cells can differentiate into retinal neurons using alternative methods or longer periods of differentiation. Retinal pigment epithelial cells Identification of retinal pigment epithelial cells as retinal stem cells: Retinal pigment epithelial cells are pigment epithelial cells that are located between retina and choroidal vascular cells. are maximally induced MI-503 to differentiate in the host eye). Among the 16 mice that received the transplant, 12 had GFP-positive cells 28 days after transplantation, and eight mice showed morphological integration and migration into the distal outer layer of the neural retina and RPE where these integrated cells expressed Rom1, a rod photoreceptor outer segment protein (8). Although these studies raise the exciting possibility that a subpopulation of human CPE cells are retinal stem cells, unresolved issues need to be considered, including the rarity of retinal stem cells (only 0.018% of single pigmented cells can give rise to clonal colonies), low yield of terminal differentiated cells, and limited potential for integration into the adult mammalian retina. Evidences against the possibility that CPE cells can differentiate into retinal stem cells have also been reported. For example, Cicero anatomical distribution of retinal progenitor cell markers. They found that Nestin-positive cells were detected only in the neural retina, which were adjacent to ora serrata, and they expressed Sox2, shh, and chx10 but were not found in ciliary epithelial cells, where only vimentin and Sox2 were expressed (35). Notably, CPE cells did not express Chx10 when they were plated under adherent conditions (34). This finding is different from the finding in Muller cells, in which Chx10 expression was observed in adherent cultures (5). However, the retinal progenitor markers Chx10 and Rx were expressed only when CPE cells were cultured under suspension culture conditions (34, 36). Recent studies showed that somatic cells can be at least partially reprogrammed during the spheroid formation process (37). Therefore, the finding Rabbit Polyclonal to RCL1 that Chx10 is MI-503 expressed only in sphere cultures of CPE cells requires further confirmation to exclude the possibility that the suspension culture itself has partial reprogramming effects on CPE cells. Additionally, further studies are needed to determine whether the cells in the regenerating retina directly differentiate from retinal stem cells or are trans-differentiated from cultured primary cells. Limitation of the potential of CPE cells as retinal stem cells: In addition to these issues on the cellular identity of CPE cells, discrepancies have been noted in the clonal proliferation and differentiation potential of various types of retinal cells. For example, one of the major discrepancies concerns the potential of human CPE cells to differentiate into rod photoreceptor cells. Subsequent research by numerous investigators adopted this criterion and reported various ranges of photoreceptor cell differentiation from CPE cells (28-32). Ballios integration and differentiation observed in NOD/SCID mice also needs to be examined further because the findings were limited to postnatal day 1 NOD/SCID mice, and such results were not evident in an adult dystrophic MI-503 RCS model. Similarly, additional studies on transplanted cells that migrate to and are integrated in the retina are warranted to examine their integrated function in the retina. Collectively, human CPE cells can express a certain range of retinal progenitor markers in spheroid form but appear to have limited potential for retinal neuronal differentiation and self-renewal. However, further studies are needed to determine whether these cells can differentiate into retinal neurons using alternative methods or longer periods of differentiation. Retinal pigment epithelial cells Identification of retinal pigment epithelial cells as retinal stem cells: Retinal pigment epithelial cells are pigment epithelial cells that are located between retina and choroidal vascular cells. Retinal pigment epithelial cells play an essential role in homeostasis and phototransduction in the retina (40). These cells are the most widely studied cell types in the retina because of their long history of being used in primary cell cultures. Accordingly, studies that use RPE cells from many species demonstrated their potential for differentiation into retinal ganglion, amacrine, photoreceptor, and glial cells (41-43). For example, Carr highlight the possibility of using RPE.