To assess the impact of mesenchymal stem/stromal cell (MSC) intra-arterial delivery through cardiopulmonary bypass (CPB) on the proliferation of neural stem/progenitor cells (NSPC) and neuroblast migration in the porcine subventricular zone (SVZ).

Congenital heart disease is a leading birth defect. Children who undergo cardiac surgery with CPB show significant cognitive/behavioral impairment. The SVZ in the postnatal brain is a crucial region for neurogenesis and neocortical growth of the gyrencephalic frontal lobes. The porcine SVZ resembles its human counterpart. Our preclinical studies have shown that CPB impairs NSPC pool and neuroblast migration toward the frontal cortex in the porcine SVZ four weeks after surgery. Others have shown that MSCs promote neurogenesis from SVZ NSPCs in early and late rodent models.

CPB/DHCA increased early proliferation of NSPCs. MSC delivery did not alter CPB-induced increased early proliferation of NSPCs. However MSC delivery reduced the length of  GFAP⁺ processes of radial-glia like cells and the amount of DCX⁺ neuroblasts in tier 1 and also increased the density of DCX⁺ cells in tiers 2 and 3 where neuroblasts migrate tangentially toward the frontal lobe. These findings suggest that MSC delivery changes neuroblasts distribution within the SVZ and promotes neuronal migration toward the frontal lobe.