Larpthaveesarp A, Pathipati P, Ostrin S, et al. - Researchers conducted this study to assess the long-term histological and functional effectiveness of enhanced, intranasal stem cell therapy [mesenchymal stromal cell (MSC) preexposed to erythropoietin( EPO)] vs standard MSC or multidose systemic EPO. Transient middle cerebral artery occlusion or sham surgery was performed in postnatal day (P) 10 Sprague-Dawley rats, who were treated with single-dose intranasal MSC, MSC preexposed to EPO (MSC/EPO), multidose systemic EPO (EPO3; 1000 u/kg per dose×3 every 72 hours), or cell-conditioned media on P13 (day 3 [P13–P19] for EPO), or on P17 (day 7 [P17–P23] for EPO). When administered at 3 or 7 days after middle cerebral artery occlusion, MSC, MSC/EPO, and EPO3 improved brain volume. Such results indicate that single-dose MSC/EPO and multi-dose systemic EPO enhance long-term neurobehavioral outcomes even with delayed administration, while overall EPO was the most successful treatment. While precise mechanisms remain to be determined, it is likely that the EPO represents a final common pathway for improved long-term repair.