Impact of Host α2-Antiplasmin Deficiency on Engraftment and the Morphological Maturation of Transplanted Neural Precursor Cells in the Mouse Brain

Abstract

Neural precursor cell (NPC) transplantation is a promising therapeutic strategy for reconstructing damaged neuronal circuits and achieving functional recovery in neurological diseases. However, the impact of the host microenvironment on the survival and maturation of transplanted cells is not fully understood. The fibrinolytic system regulates clot lysis and extracellular matrix remodeling through proteolytic activity, but its role in neuronal maturation following NPC transplantation remains to be elucidated. This study investigated whether host deficiency of α2-antiplasmin (α2AP), the primary inhibitor of plasmin, affects the engraftment and maturation of transplanted NPCs in the mouse brain. Green fluorescent protein-expressing mouse embryonic stem cell-derived NPCs were transplanted into the brains of wild-type (WT) and α2AP-knockout (KO) mice. Graft size and cell survival were comparable between WT and α2AP-KO mice, suggesting that host α2AP deficiency does not affect engraftment efficiency. In contrast, the number of neurites in transplanted neurons tended to be lower in α2AP-KO mice, particularly in DCX-positive immature neurons. These findings suggest that α2AP in the host environment may contribute to the morphological maturation of transplanted neurons rather than to their survival and differentiation.