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Jean M. Lawrencea, Shweta Singhala, Bhairavi Bhatiaa, David J. Keegana, Thomas A. Rehb, Philip J. Lutherta, Peng T. Khawa, Gloria Astrid Limba
aOcular Repair and Regeneration Biology Unit, Departments of Cell Biology and Pathology, Institute of Ophthalmology and Moorfields Eye Hospital, London, United Kingdom;
Key Words. Adult stem cells • Cellular proliferation • Glial differentiation • Glia • Neural differentiation • Retinal transplantation Stem/progenitor cell • Tissue-specific stem cells
Correspondence: Gloria Astrid Limb, Ph.D., Ocular Repair and Regeneration Biology Unit, Departments of Cell Biology and Pathology, Institute of Ophthalmology, 11 Bath Street, London EC1V 9EL, U.K. Telephone: 020 7608-6974; Fax: 020 7608-4034;
bDepartment of Biological Structure, University of Washington, Seattle, Washington, USA
Received November 8, 2006; accepted for publication May 9, 2007.
First published online in STEM CELLS EXPRESS May 24, 2007.
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 postnatal 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 epidermal growth factor, 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 fibroblast growth factor-2 or retinoic acid, they acquired neural morphology, formed neurospheres, and expressed neural stem cell markers including ßIII tubulin, Sox2, Pax6, Chx10, and Notch 1. They also expressed markers of postmitotic retinal neurons, including peripherin, recoverin, calretinin, S-opsin, and Brn3. When grafted into the subretinal space of dystrophic Royal College of Surgeons 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 harbors 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.
Disclosure of potential conflicts of interest is found at the end of this article.
