Systemic Neurotransplantation - A Problem-Oriented Systematic Review

Abstract

Systemic neurotransplantation (SNT) was introduced in the laboratory in 2000 and currently it is being widely examined in animal models of neurological disorders. The aim of this systematic review was to evaluate the current state of knowledge in the field of experimental SNT and the premise for the introduction of clinical trials. PubMed was searched and 60 articles utilizing an SNT approach were found and subjected to analysis. The time window for cell transplantation was addressed in only two studies, with contradictory results. Immunosuppression was applied in 25% of studies. No study addressed the justification for immunosuppression. Bone marrow was the most frequent source of grafted cells, followed by cord blood and then by cells of embryonic origin. Studies investigating dose-dependency revealed no satisfactory results with transplantation of less than 10(6) cells/animal; the efficient dose most frequently ranged from 10(6)-10(7) cells/animal (mice and rats). The behavioral effects of cell transplantation were assessed in 75% of all studies; significant improvement was achieved in 95% of them. Morphological effect was evaluated in half of the studies; significant positive effect was achieved in 73% of them. Experimental attempts to elucidate the mechanisms mediating cell-dependent effect were not undertaken in half of the studies. In the other half, the most frequent mechanisms were growth factors, neurogenesis and immunomodulation. SNT still seems to be at the very initial stage of development. Many critical factors have not been sufficiently addressed in laboratory studies and they must be clarified before the introduction of clinical trials.