The fate of heterotopically grafted neural precursor cells in the normal and dystrophic adult mouse retina

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 beta2/beta1 knock-in mice. Beta2/beta1 knock-in mutants display apoptotic death of photoreceptor cells and were generated by placing the cDNA of the beta1 subunit into the gene of the beta2 subunit of Na,K-ATPase. The integration and differentiation of grafted cells in recipient retinas was studied 1 or 6 months after transplantation.

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.