Survival of grafted fetal neural cells in kainic acid lesioned CA3 region of adult hippocampus depends upon cell specificity.
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abstract
We hypothesize that the degree of graft cell survival within the damaged CNS correlates with the specificity of donor cells to the region of grafting. We investigated graft cell survival following transplantation of fetal micrografts into the CA3 region of the adult rat hippocampus at a time-point of 4 days after an intracerebroventricular administration of kainic acid (KA). Grafts consisted of 5'-bromodeoxyuridine (BrdU) labeled embryonic day (E) 19 cells from hippocampal fields CA3 and CA1 and E15 and E19 cells from the striatum. Absolute cell survival in these grafts was quantitatively analyzed at 1 month postgrafting, using BrdU immunostaining of serial sections and three-dimensional reconstruction of grafts. Absolute graft cell survival in lesioned CA3 was dramatically greater for cells having hippocampal origin (CA3 cells, 69% cell survival; CA1 cells, 42% cell survival) than those having nonhippocampal origin, such as striatal cells (E15 cells, 12% cell survival; E19 cells, 4% cell survival). This difference is in sharp contrast to survival of these cells in culture, where E19 cells from both hippocampal and nonhippocampal origins exhibited similar survival. Comparison of survival among hippocampal cell types indicated significantly greater survival for cells that are specific to the lesioned area (i.e., CA3 cells) than for those that are nonspecific to the lesioned area (i.e., CA1 cells). Graft cell survival in the intact CA3 region (contralateral to KA administration), however, did not differ either between cells having hippocampal and nonhippocampal origins or between CA3 and CA1 cells (CA3 cells, 26% cell survival; CA1 cells, 33% cell survival; and E15 striatal cells, 20% cell survival). These results underscore the finding that enhanced survival of fetal cell grafts in the lesioned CNS is critically dependent upon the specificity of donor fetal cells to the region of transplantation. Thus, grafting of cells that are specific to the lesioned area is a prerequisite for achieving maximal graft cell survival and integration in the lesioned host CNS.
