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(Investigative Ophthalmology and Visual Science. 2003;44:426-434.)
© 2003 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.02-0269

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Incorporation of Murine Brain Progenitor Cells into the Developing Mammalian Retina

Samantha J. Van Hoffelen,1,2 Michael J. Young,3 Marie A. Shatos,3 and Donald S. Sakaguchi1,2

1From the Department of Zoology and Genetics and the 2Neuroscience Program, Iowa State University, Ames, Iowa; and the 3Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts.

PURPOSE. To investigate the influence of a developing host environment on the survival, differentiation, and morphologic integration of murine brain progenitor cells (mBPCs) transplanted into the mammalian retina.

METHODS. Enhanced green fluorescent protein (GFP)–expressing murine brain progenitor cells were transplanted into developing and mature Brazilian opossums (Monodelphis domestica). Animals were allowed to survive for up to 4 weeks after transplantation, at which time the eyes were prepared for immunohistochemical analysis.

RESULTS. Transplanted mBPCs survived and differentiated in vivo, and extensive morphologic integration was observed within the host retinas. GFP-expressing cells often displayed morphologies characteristic of retinal neurons. GFP somata were located in nuclear layers, and their processes ramified throughout the inner (IPL) and outer (OPL) plexiform layers. Furthermore, in some cases, GFP-expressing neurites were confined to specific sublamina within the IPL. The greatest morphologic integration and differentiation were observed after transplantation into the youngest-aged host eyes. Some transplanted mBPCs incorporated within the inner retina expressed the neuronal markers microtubule associated protein (MAP)-2 or calretinin. Transplanted cells coexpressed GFP and recoverin only in the ONL.

CONCLUSIONS. mBPCs survived and morphologically integrated after xenotransplantation without immunosuppression. mBPCs were capable of incorporating into specific layers of the retina and expressing neuronal and retinal markers. The age of the host appeared to play a key role in determining cell fate in vivo.





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