TY - JOUR
T1 - The fate of heterotopically grafted neural precursor cells in the normal and dystrophic adult mouse retina
AU - Pressmar, Susanne
AU - Ader, Marius
AU - Richard, Gisbert
AU - Schachner, Melitta
AU - Bartsch, Udo
PY - 2001
Y1 - 2001
N2 - 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 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.
AB - 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 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.
UR - http://www.scopus.com/inward/record.url?scp=0035650580&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035650580&partnerID=8YFLogxK
M3 - Article
C2 - 11726638
SN - 0146-0404
VL - 42
SP - 3311
EP - 3319
JO - Investigative Ophthalmology and Visual Science
JF - Investigative Ophthalmology and Visual Science
IS - 13
ER -