Transplantation of glial progenitor and neural stem cells into
the normal and diseased retina
Gisbert Richard, U. Bartsch (Hamburg)
Purpose: To evaluate the use of intraretinal transplantations of oligodendrocyte
progenitor
cells (OPCs) to study axon-oligodendrocyte interactions in vivo, and
of
intraretinal transplantations of neural stem cells (NSCs) and retinal
stem cells
(RSCs) to treat retinal dystrophies.
Methods: OPCs were isolated from cerebral hemispheres of neonatal rats,
NSCs from
the spinal cord of embryonic mice, and RSCs from the ciliary margin of
the adult
mouse eye. OPCs were grafted into the retina of young rats, and NSCs
were grafted
into the dystrophic retina of adult ß2/ß1 knock-in mutant
mice. RSCs were characterized in vitro.
Results: Numerous oligodendrocytes were present in the nerve fiber layer
of host retinas one month after transplantation
of OPCs. Donor-derived oligodendrocytes myelinated a large portion of
the nerve fiber layer of experimental
retinas, and formed ultrastructurally intact myelin around ganglion cell
axons. NSCs integrated extensively
into retinas of adult ß2/ß1 knock-in mice and populated all
retinal layers, including the outer nuclear
layer. NSCs survived for extended periods of time in host retinas, and
differentiated into astrocytes and myelinforming
oligodendrocytes, but not into nerve cells. Cells with properties characteristic
of RSCs were isolated
from the ciliary margin of the adult mouse eye.
Conclusions: Extensive myelination of intraretinal segments of ganglion cell axons
after transplantation of
OPCs demonstrates the competence of these axons to become myelinated
along their entire length. We thus
conclude that non-neuronal factors at the retinal end of the optic
nerve prevent migration of OPCs from the
nerve into the retina, and as a consequence intraretinal myelination.
Intraretinally grafted NSCs integrate into
the dystrophic retina of adult mice and differentiate into neural cell
types, but fail to differentiate into retinal
cell types. Cell therapy of dystrophic retinas thus requires the availability
of stem cells displaying the ability to
differentiate into retina-specific cell types. Pigmented cells from
the ciliary margin of the adult mammalian eye
show characteristics of stem cells, and differentiate into retina-specific
glial and neuronal cell types in vitro.