Transplantation of hippocampal cell lines restore spatial learning in rats with ventral subicular lesions.

Abstract

We have demonstrated in our previous studies that ventral subicular lesion induces neurodegeneration of the hippocampus and produces cognitive impairment in rats. In the present study, the efficacy of transplanted green fluorescent protein (GFP)-labeled hippocampal cell line (H3-GFP) cells in establishing functional recovery in ventral subicular lesioned rats has been evaluated. The survival of H3-GFP transplants and their ability to express trophic factors in vivo were also investigated. Adult male Wistar rats were subjected to selective lesioning of ventral subiculum and were transplanted with H3-GFP cells into the cornu ammonis 1 (CA1) hippocampus. The transplants settled mainly in the dentate gyrus and expressed neurotrophic factors, brain-derived neurotrophic factor (BDNF), and basic fibroblast growth factor (bFGF). The ventral subicular lesioned (VSL) rats with H3-GFP transplants showed enhanced expression of BDNF in the hippocampus and performed well in eight-arm radial maze and Morris water maze tasks. The VSL rats without hippocampal transplants continued to show cognitive impairment in task learning. The present study demonstrated the H3-GFP transplants mediated recovery of cognitive functions in VSL rats. Our study supports the notion of graft meditated host regeneration and functional recovery through trophic support, although these mechanisms require further investigation.

Infusion of human embryonic kidney cell line conditioned medium reverses kainic acid induced hippocampal damage in mice

“…In contrast, these behavioral deficits were completely ameliorated in hippocampaldamaged mice that received intravenous injections of HEK cells or HEK-CM. This observation is consistent with the previous reports that cell therapies could ameliorate behavioral deficits in animal models of hippocampal neurodegeneration [6,7]. However, the current study is the first of its kind to demonstrate that infusion of HEK-CM per se could effectively ameliorate co-morbidities that are commonly observed in hippocampal-impaired subjects.…”

“…Hippocampal damage also leads to mood instability such as depression, which in turn affects an individual's day-to-day life severely [26]. Several studies have shown the beneficial effects of cell therapies in ameliorating hippocampal cell death and behavioral abnormalities in animal models of hippocampal degeneration [6,7]. In the present study, behavioral deficits were readily identifiable in hippocampal damaged mice because these mice were unable to discriminate between familiar and novel objects, and these mice displayed severe depressionlike symptoms.…”

“…In this context, conditioned media (CM) derived from cell cultures are excellent sources of neurotrophic factors and cytokines [11,12]. Though the majority of studies investigated the effects of cell transplantation in animal models of hippocampal neurodegeneration [6,7], there is not much information available on the effects of CM per se in cellular and behavioral recovery after hippocampal damage.…”

Regenerative therapy for hippocampal degenerative diseases: lessons from preclinical studies

“…Thus, there is a pressing need to identify alternative therapeutic strategies to arrest the progression of neurodegeneration. Cell therapy is emerging as a potential therapeutic modality against neurodegenerative diseases (Li et al ., , ; Maisano et al ., ; Rekha et al ., ). Two possible avenues through which functional recovery could be achieved include stimulation, followed by mobilization of endogenous stem cells towards the vicinity of degenerating sites (Diederich et al ., ; Li et al ., ; Sehara et al ., ), or transplanting exogenous neural cells that can proliferate and replace the lost neurons (Maisano et al ., 2009; Rekha et al ., , ).…”

“…Cell therapy is emerging as a potential therapeutic modality against neurodegenerative diseases (Li et al ., , ; Maisano et al ., ; Rekha et al ., ). Two possible avenues through which functional recovery could be achieved include stimulation, followed by mobilization of endogenous stem cells towards the vicinity of degenerating sites (Diederich et al ., ; Li et al ., ; Sehara et al ., ), or transplanting exogenous neural cells that can proliferate and replace the lost neurons (Maisano et al ., 2009; Rekha et al ., , ). The concept of adult neurogenesis is now widely acknowledged and is known to occur in two brain regions, the subventricular zone (SVZ) and the subgranular zone (SGZ) of the DG (Deng et al ., ; Li et al ., ; Suh et al ., ; Thuret et al ., ; van Praag et al ., ).…”