Predifferentiated brain-derived adult human progenitor cells migrate toward ischemia after transplantation to the adult rat brain.

BACKGROUND

The adult human brain contains neural stem/progenitor cells (AHNPCs) that can survive transplantation into the adult rat brain, migrate toward a lesion, and display limited neuronal differentiation in vivo.

OBJECTIVE

To investigate the effect of manipulating AHNPCs before grafting by predifferentiation, ie, initiating neuronal differentiation before transplantation, and to determine whether this cell priming would affect their ability to migrate in vivo.

METHODS

AHNPCs were prepared from temporal lobe resections for epilepsy. Seven days after global brain ischemia, predifferentiated AHNPCs (exposed to basic fibroblast growth factor, heparin, and laminin) were transplanted to the left hippocampus. Four and 10 weeks after transplantation, brain sections were analyzed by immunohistochemistry.

RESULTS

Transplanted primed cells expressed committed neuronal markers at a much earlier stage compared with nonprimed AHNPCs and were found colabeled with human markers within the damaged CA1 region 4 weeks after grafting. Furthermore, predifferentiated AHNPCs migrated preferentially into an ischemic lesion, similar to their undifferentiated counterparts. The chemoattractant effect from the expression of stromal cell-derived factor-1α (SDF-1α) in ischemic CA1 on AHNPCs expressing CXC chemokine receptor 4 (CXCR4) may explain this preference in migration in vivo.

CONCLUSION

The plasticity of neural progenitors derived from the adult human brain may be greater than previously assumed in that manipulation before grafting may influence the phenotypes seen in vivo. The SDF-1α-CXCR4 axis is involved in the targeted migration toward an ischemic lesion in the adult rat brain, similar to previous reports on endogenous progenitors in rats and grafted fetal human neural progenitors.