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Susanne Pressmar, Marius Ader, Gisbert Richard, Melitta Schachner, Udo Bartsch; The Fate of Heterotopically Grafted Neural Precursor Cells in the Normal and Dystrophic Adult Mouse Retina. Invest. Ophthalmol. Vis. Sci. 2001;42(13):3311-3319.
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purpose. To study the integration and differentiation of heterotopically
transplanted neural precursor cells in the retina of adult mouse
mutants displaying apoptotic degeneration of photoreceptor cells.
methods. Neural precursor cells were isolated from the spinal cord of transgenic
mouse embryos ubiquitously expressing enhanced green fluorescent
protein. Cells were expanded in vitro and transplanted into the retina
of adult wild-type and age-matched β2/β1 knock-in mice. β2/β1
knock-in mutants display apoptotic death of photoreceptor cells and
were generated by placing the cDNA of the β1 subunit into the gene of
the β2 subunit of Na,K-ATPase. The integration and differentiation of
grafted cells in recipient retinas was studied 1 or 6 months after
results. Mutant retinas contained more donor-derived cells than wild-type hosts.
Moreover, in mutants, donor cells integrated into deeper retinal
layers. In both genotypes, grafted cells differentiated into astrocytes
and oligodendrocytes. Only a few ganglion cell axons were myelinated by
donor-derived oligodendrocytes 1 month after transplantation, whereas
extensive myelination of the nerve fiber layer was observed 6 months
after transplantation. Unequivocal evidence for differentiation of
grafted cells into neurons was not obtained.
conclusions. Heterotopically transplanted neural precursor cells are capable of
integrating, surviving, and differentiating into neural cell types in
normal and dystrophic retinas of adult mice. The particular environment
of a pathologically altered retina facilitates integration of
transplanted precursor cells. In principle, neural precursors may thus
be useful to substitute for or replace dysfunctional or degenerated
cell types. Results of the present study also indicate that replacement
of retinal cell types is likely to require more appropriate donor
cells, such as retinal precursor cells.
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