Transplanted Dentate Progenitor Cells Show Increased Survival in an Enriched Environment but Do Not Exert a Neurotrophic Effect on Spatial Memory within 2 Weeks of Engraftment

Abstract

Cyclin D2 knockout mice show decreased levels of endogenous dentate neurogenesis. We investigated whether transplanted dentate progenitor cells from wild-type mice respond in vivo to an enriched environment and whether they improve deficient dentate neurogenesis through a neurotrophic effect. Adult cyclin D2 knockout mice were transplanted with passaged adult progenitor cells and kept in an enriched environment or under standard housing conditions in isolation. After 1 week, animals living in an enriched environment underwent water maze testing. Progenitor cells grown on a laminin/poly-d-lysine monolayer expressed Sox2 and nestin and could be differentiated in vitro into neurons and astrocytes. After transplantation into the dentate gyrus, cells preferentially survived along the laminin-rich ependymal lining of the basal cistern or basal membrane of capillaries. A subpopulation of transplanted cells migrated into the interstitial space of the hippocampus and was not associated with laminin. Environmental enrichment led to a significant increase in the survival of transplanted progenitor cells on laminin in the dentate gyrus after 2 weeks. However, animals did not show an enhanced performance in the Morris water maze, and transplantation failed to exert a neurotrophic effect on endogenous neurogenesis after 2 weeks. However, a major limitation of the study is the short-term period of investigation, which may have been insufficient to capture functional effects. In conclusion, initial survival of transplanted neural progenitor cells was dependent on the presence of laminin and was significantly enhanced by environmental enrichment. Further studies are needed to address whether an enriched environment continues to promote graft survival over longer periods of time.

Adult Neural Stem Cells from Midbrain Periventricular Regions Show Limited Neurogenic Potential after Transplantation into the Hippocampal Neurogenic Niche

“…Transplantation studies are one possibility to enlighten the interplay between cell-intrinsic and cell-extrinsic factors in the regulation of aNSC properties and have been carried out in a variety of transplantation sites with various graft origins: the homotopic transplantation of PVR V-SVZ aNSCs provided large numbers of neurons with a typical olfactory bulb interneuron morphology [ 44 ], but other studies using heterotopic grafting of either PVR V-SVZ aNSCs or neuroblasts yielded contradictory results, with either a predominant astroglial or neuronal differentiation independent of host specifications such as increased age or dopaminergic differentiation [ 45 , 46 , 47 , 48 , 49 ]. Similarly, hippocampal aNSCs display a robust neuronal differentiation after homo- and heterotopic grafting into neurogenic regions, but a strict astroglial differentiation otherwise [ 50 , 51 , 52 , 53 ]. A recent study even reported the acquisition of neuronal properties of grafted aNSCs through a fusion with resident neurons of the host brain [ 54 ].…”