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S.C. McLoon; Repopulation of the Outer Nuclear Layer by Bone Marrow–Derived Stem Cells in an Animal Model of Retinitis Pigmentosa . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1765.
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© ARVO (1962-2015); The Authors (2016-present)
Previous studies showed that a non–hematopoetic stem cell isolated from adult bone marrow (MSCs) can be induced to differentiate into many cell types including neurons. MSCs readily divide in culture and exhibit minimal chromosomal abnormalities after many doublings. Unlike certain other stem cell types, MSCs have not formed teratomas in a variety of in vivo environments. We are investigating the possibility of using MSCs for replacement of photoreceptor cells lost due to degenerative disease.
Plastic–adherent, CD–45 negative mononuclear cells were isolated from the femur of adult rats. These MSCs were stably transfected with GFP and expanded in culture. In some cases, the MSCs were also transfected with Crx or Crx and Nrl. Crx and Nrl are transcription factors essential for photoreceptor cell development. The MSCs were injected subretinally in adult P23H rats. P23H rats carry a rhodopsin mutation identical to that linked to a human form of retinitis pigmentosa and exhibit adult onset photoreceptor degeneration. One to eight weeks following the stem cell injection, the eyes of the animals were fixed and analyzed histologically.
Following the subretinal injection of MSCs transfected with GFP alone or with GFP and Crx, isolated GFP–positive cells were present in all layers of the host retina. These cells showed limited signs of position–appropriate differentiation. In no case did the cells contribute significantly to the outer nuclear layer. Injection of MSCs transfected with GFP, Crx and Nrl resulted in a significant increase in the number of cells in the host outer nuclear layer. GFP–positive cells accumulated along the outer border of the outer nuclear layer near the site of the subretinal injection, and GFP–positive processes could be followed from the cell bodies into the layers of inner and outer segments in some cases. The GFP–positive cells in the outer nuclear layer also appeared to be positive for a number of photoreceptor markers including rhodopsin.
These initial results suggest that MSCs transfected with Crx and Nrl and injected subretinally migrate to the appropriate cell layer and differentiate as photoreceptor cells in a host retina with photoreceptor degeneration.
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