Neural progenitor cell transplants into the developing and mature central nervous system.

When developing cell transplant strategies to repair the diseased or injured central nervous system (CNS), it is essential to consider host-graft interactions and how they may influence the outcome of the transplants. Recent studies have demonstrated that transplanted neural progenitor cells (NPCs) can differentiate and integrate morphologically into developing mammalian retinas. Is the ability to differentiate and to undergo structural integration into the CNS unique to specific progenitor cells, or is this plasticity a function of host environment, or both? To address these issues we have used the developing retina of the Brazilian opossum and have compared the structural integration of brain and retinal progenitor cells transplanted into the eyes at different developmental stages. The Brazilian opossum, Monodelphis domestica, is a small pouchless marsupial native to South America. This animal's lack of a pouch and fetal-like nature at birth circumvents the need for in utero surgical procedures, and thus provides an ideal environment in which to study the interactions between developing host tissues and transplanted NPCs. To test whether NPCs affect visual function we transplanted adult hippocampal progenitor cells (AHPCs) into normal, healthy adult rat eyes and performed noninvasive functional recordings. Monitoring of the retina and optic nerve over time by electroretinography and pupillometry revealed no severe perturbation in visual function in the transplant recipient eyes. Taken together, our findings suggest that the age of the host environment can strongly influence NPC differentiation and that transplantation of neural progenitor cells may be a useful strategy aimed at treating neurodegeneration and pathology of the CNS.

Transplantation of neural progenitor cells into the developing retina of the Brazilian opossum: an in vivo system for studying stem/progenitor cell plasticity.

In developing cell transplant strategies to repair the diseased or injured retina is essential to consider host-graft interactions and how they may influence the outcome of the transplants. In the present study we evaluated the influence of the host microenvironment upon neural progenitor cells (NPCs) transplanted into the developing and mature retina of the Brazilian opossum, Monodelphis domestica. Monodelphis pups are born in an extremely immature state and the neonatal pups provide a fetal-like environment in which to study the interactions between host tissues and transplanted NPCs. Three different populations of GFP-expressing NPCs were transplanted by intraocular injection in hosts ranging in age from 5 days postnatal to adult. Extensive survival, differentiation and morphological integration of NPCs were observed within the developing retina. These results suggest that the age of the host environment can strongly influence NPC differentiation and integration.

Differentiation and morphological integration of neural progenitor cells transplanted into the developing mammalian eye.

Transplantation of neural stem/progenitor cells has been proposed as a novel approach for the replacement and repair of damaged CNS tissues. We have evaluated the influence of the host cellular microenvironment upon the survival, differentiation, and integration of neural progenitor cells transplanted into the CNS. Using this approach, we have investigated the fate of neural progenitor cells in vivo following transplantation into the developing mammalian eye. Murine brain progenitor cells (mBPCs) isolated from neonatal mice expressing the green fluorescent protein (GFP) transgene were transplanted into the eyes of Brazilian opossums (Monodelphis domestica). Monodelphis pups are born in an extremely immature, fetal-like state. The eyes of neonatal pups provide a fetal-like environment in which to study cellular interactions between host tissues and transplanted neural progenitor cells. mBPCs were transplanted by intraocular injection in hosts ranging in age from 5 days postnatal to adult. The transplanted cells were easily identified because of their GFP fluorescence. Extensive survival, differentiation, and morphological integration of mBPCs within the host tissue was observed. We found that the younger retinas provided a more supportive environment for the morphological integration of the transplanted mBPCs. Cells with morphologies characteristic of specific retinal cell types were observed. Moreover, some transplanted mBPCs were labeled with antibodies characteristic of specific neural/retinal phenotypes. These results suggest that the host environment strongly influences progenitor cell differentiation and that transplantation of neural progenitor cells may be a useful approach aimed at treating degeneration and pathology of the CNS.