Enabling Survival of Transplanted Neural Precursor Cells in the Ischemic Brain

Abstract

There is no effective therapy for ischemic stroke following the acute stage. Neural transplantation offers a potential option for repairing the ischemic lesion. However, this strategy is hindered by the poor survival of the neural precursor cells (NPCs) that are transplanted into the inflammatory ischemic core. Here, a chemical cocktail consisting of fibrinogen and maraviroc is developed to promote the survival of the transplanted NPCs in the ischemic core of the mouse cerebral cortex. The grafted NPCs survive in the presence of the cocktail but not fibrinogen or maraviroc alone at day 7. The surviving NPCs divide and differentiate to mature neurons by day 30, reconstituting the infarct cortex with vascularization. Molecular analysis in vivo and in vitro shows that blocking the activation of CCR5 on the NPCs protects the NPCs from apoptosis induced by pro-inflammatory factors, revealing the underlying protective effect of the cocktail for NPCs. The findings open an avenue to enable survival of the transplanted NPCs under the inflammatory neurological conditions like stroke.

Keywords: CCR5 antagonists; fibrinogen; ischemic strokes; neural regenerations; transplantations.