Vascularization and microvascular permeability in solid versus cell-suspension embryonic neural grafts

Vascularization and microvascular permeability were assessed in a comparative study of solid (organized) and cell-suspension (dissociated) fetal nigral grafts implanted in the dopamine-deprived striatum of adult rats. Both graft types were analyzed by chromogen detection of intravenously injected horseradish peroxidase (HRP), which outlined vessel walls, and, in cases in which the blood-brain barrier was compromised, permeated the graft and host parenchyma. Survival of graft-derived dopaminergic cells was assessed using tyrosine hydroxylase (TH) immunocytochemistry. Glial reactivity to cell-suspension grafts was similarly assessed with an antibody directed against glial fibrillary acidic protein. Morphometry revealed significantly higher microvessel density in the cell-suspension grafts (p < 0.001), which effectively equaled that found in the contralateral striatum despite rather prominent surrounding glial reactivity. Capillaries in the cell-suspension grafts were not permeable to blood-borne HRP at postimplantation study times of 7, 14, and 30 days whereas, in the solid grafts, permeability in some cases could be detected for up to 30 days. Large numbers of cells immunoreactive for TH were seen in cell-suspension grafts; in contrast, few if any were found in the majority of solid transplants. The multiple-fragment solid graft implant model used clinically compares poorly with the cell-suspension model because it lacks consistency in early revascularization and shows a greater (albeit temporary) tendency for blood-brain barrier dysfunction. Delayed and inadequate vascularization of the solid graft is likely to account for graft failure more often than in the cell-suspension graft. Similarly, a certain critical number of specific grafted cells are required to achieve sufficient expression to bring about a favorable response in the disabled host, and this expression appears to be achieved less consistently with the solid implant technique.