Although mammals do not share the innate capacity for retinal regeneration displayed by many teleost, urodele, and anuran species, there is now a sizeable literature documenting the restorative selleck kinase inhibitor potential of transplanted stem and progenitor cells in animal models retinal disease (as reviewed in [1]). The types of stem and stem-like cells that have been used as donor cells for retinal transplantation range from embryonic stem cell [2] and induced pluripotent stem (iPS) cells [3] to brain- and retina-derived CNS progenitor cells [4, 5], primary rod photoreceptor precursor cells [6], and bone marrow-derived populations such as vascular progenitors [7]. Gratifying results have been frequently reported, regardless of cell type, although here it should be noted that a number of caveats apply.

Pluripotent cells typically require partial predifferentiation into lineage-committed progenitor cells prior to transplantation to improve the yield of desired mature cell type and to avoid teratoma formation. Photoreceptor precursors can be enriched from immature transgenic murine tissue, but the isolation of clinically significant yields of human precursors has not yet Inhibitors,Modulators,Libraries been possible such Inhibitors,Modulators,Libraries that the translation of this approach will likely require additional Inhibitors,Modulators,Libraries scientific advances. Currently, bone marrow and CNS progenitors are particularly attractive from the standpoint of preclinical development, and of these, the latter has the added advantage of exhibiting the capacity for neuronal cell replacement in the diseased retina.

CNS progenitor cells have now been derived from the brain or the retina of multiple different mammalian species, including humans [8], and transplanted to the retina of the mouse [9], rat Inhibitors,Modulators,Libraries [4, 9, 10], Brazilian opossum [11], pig [12�C14], cat [15], and monkey [16]. Donor cell survival has been consistently reported over a varying range of survival times. In none of these instances were the cells autologous, and in the majority of cases, the recipient animals did not receive immune suppression. The ability of allogeneic CNS progenitor cells to survive transplantation to immune competent hosts is robust and reproducible, but not invariant, as has been particularly well characterized in the mouse [17].

The apparent immune privilege status of CNS progenitors as donor cells is a factor that might enhance Inhibitors,Modulators,Libraries the clinical utility of these cells although an important caveat here is attention to treatment conditions that might influence expression of the major histocompatibility complex (MHC), particularly class II antigens [18]. In addition to allografting experiments, CNS progenitors have been transplanted to the vitreous Brefeldin_A and retina as xenografts. For instance, grafts of brain-derived GFP+ murine NPCs have been performed in the rat [10] and the Brazilian opossum [11], in both cases without immune suppression.