Pretreatment of donor cells with FGF-2 enhances survival of fetal hippocampal CA3 cell transplants in the chronically lesioned young adult hippocampus.
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abstract
The lesioned CA3 region of the young adult hippocampus is very conducive for robust survival and integration of fetal hippocampal CA3 cell grafts when transplanted at an early postlesion delay of 4 days. However, similar CA3 cell grafts placed at 45 days postlesion display significantly diminished cell survival, implying that the receptivity of the lesioned young adult host hippocampus to grafts decreases considerably with a prolonged postlesion transplantation delay. We hypothesize that decreased cell survival in grafts placed into the chronically lesioned hippocampus is due to a reduced level of host neurotrophic factors that support fetal hippocampal cells; hence, pretreatment and grafting of donor fetal CA3 cells with fibroblast growth factor-2 (FGF-2) considerably enhances graft neuronal integration into the chronically lesioned young adult hippocampus. We employed the optical fractionator cell counting method and rigorously quantified the number of surviving cells and neurons derived from 5'-bromodeoxyuridine-labeled Embryonic Day 19 CA3 cell grafts pretreated and transplanted with FGF-2 into the lesioned CA3 region of the young adult rat hippocampus, at a delay of 60 days after a unilateral intracerebroventricular administration of the kainic acid. For comparison, we also analyzed the survival of standard fetal CA3 cell grafts (i.e., without FGF-2 treatment) after similar transplantation. Pre treatment and transplantation of CA3 cell grafts with FGF-2 resulted in a robust yield of surviving cells (115% of injected cells) and neurons (100% of injected cells) from grafts. In contrast, standard CA3 cell grafts exhibited a reduced yield of surviving cells (29%) and neurons (25%). Thus, the yield of neurons from fetal hippocampal CA3 cell grafts placed into the chronically lesioned young adult hippocampus can be greatly enhanced by a simple pretreatment and grafting of donor fetal CA3 cells with FGF-2. These results have significance toward advancement of clinically feasible cell grafting strategies for repair of the damaged young adult hippocampus, particularly at extended periods after the injury or the onset of neurodegenerative diseases.
