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TISSUE-SPECIFIC STEM CELLS |
1 Ocular Repair and Regeneration Biology Unit, Departments of Cell Biology and Pathology, Institute of Ophthalmology and Moorfields Eye Hospital, London, EC1V 9EL, UK
2 Department of Biological Structure, University of Washington, Box 357420, Seattle, WA 98195, USA
* To whom correspondence should be addressed. E-mail: g.limb{at}ucl.ac.uk.
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Abstract |
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Growing evidence suggests that glial cells may have a role as neural precursors in the adult central nervous system. Although it has been shown that Müller cells exhibit progenitor characteristics in the post-natal chick and rat retinae, their progenitor-like role in developed human retina is unknown. We first reported the Müller glial characteristics of the spontaneously immortalized human cell line MIO-M1, but recently we have derived similar cell lines from the neural retina of several adult eye donors. Since immortalization is one of the main properties of stem cells, we investigated whether these cells expressed stem cell markers. Cells were grown as adherent monolayers, responded to EGF and could be expanded indefinitely without growth factors under normal culture conditions. They could be frozen and thawed without losing their characteristics. In the presence of extracellular matrix and FGF2 or retinoic acid, they acquired neural morphology, formed neurospheres and expressed neural stem cell markers including III tubulin, Sox-2, Pax-6, Chx10 and Notch-1. They also expressed markers of post-mitotic retinal neurons, including peripherin, recoverin, calretinin, S-opsin and Brn3. When grafted into the subretinal space of dystrophic RCS rats or neonatal Lister hooded rats, immortalized cells migrated into the retina, where they expressed various markers of retinal neurons. These observations indicate that adult human neural retina harbours a population of cells that express both Müller glial and stem cell markers, and suggest that these cells may have potential use for cell-based therapies to restore retinal function.
Key Words. Adult stem cells, Cellular proliferation, Glial differentiation, Glia, Neural differentiation, Retinal transplantation, Stem/progenitor cell
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