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TISSUE-SPECIFIC STEM CELLS

A Comparison of Neural Differentiation and Retinal Transplantation with Bone Marrow-Derived Cells and Retinal Progenitor Cells

^aThe Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA;
^bDepartment of Reproductive Biology and Pathology, National Research Institute for Child Health and Development, Tokyo, Japan;
^cDepartment of Pathology, Keio University, Tokyo, Japan

Key Words. Bone marrow stromal cells • Microglia • Retinal stem cells • Retinal transplantation • Neural differentiation

Correspondence: Minoru Tomita, M.D., Ph.D., The Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, 20 Staniford St., Boston, Massachusetts 02114, USA. Telephone: 1-617-912-7419; Fax: 1-617-912-0101; Minoru Tomita: e-mail: tomita{at}vision.eri.harvard.edu; or Michael J. Young, Ph.D.: e-mail: mikey{at}vision.eri.harvard.edu

Received October 12, 2005; accepted for publication May 23, 2006.


Retinal progenitor cells (RPCs) are immature precursors that can differentiate into retinal neurons, including photoreceptors. Recently, it has been reported that bone marrow-derived cells may also be capable of differentiation into cells of central nervous system lineage, including retinal neurons. We compared these two cell types to evaluate their potential as a source of cells for retinal transplantation. Marrow stromal cells (MSCs) and macrophages were isolated from enhanced green fluorescence protein mice. MSCs were cultured with brain-derived neurotrophic factor, nerve growth factor, and basic fibroblast growth factor to induce neuronal differentiation. RPCs were cultured under the same conditions or with 10% fetal bovine serum. Neuronal marker expression was examined and compared between MSCs and RPCs. MSCs, macrophages, and RPCs were also cultured with explanted retinas from rhodopsin knockout mice to study their potential for retinal integration. MSCs expressed neuronal and retina-specific markers by reverse transcription-polymerase chain reaction and immunocytochemistry. Both types of cells migrated into retinal explants and expressed neurofilament 200, glial fibrillary acidic protein, protein kinase C-, and recoverin. RPCs expressed rhodopsin, a photoreceptor marker we never detected in MSCs. A majority of bone marrow derived-macrophages differentiated into cells that resembled microglia, rather than neural cells, in the explanted retina. This study shows that RPCs are likely to be a preferred cell type for retinal transplantation studies, compared with MSCs. However, MSCs may remain an attractive candidate for autologous transplantation.

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