Bone marrow mononuclear cells exert long-term neuroprotection in a rat model of ischemic stroke by promoting arteriogenesis and angiogenesis

Abstract

Transplanted bone marrow-derived mononuclear cells (BMMNCs) can promote arteriogenesis and angiogenesis by incorporating into vascular walls and differentiating into smooth muscle cells (SMCs) and endothelial cells (ECs). Here, we explored whether BMMNCs can enhance arteriogenesis and angiogenesis and promote long-term functional recovery in a rat model of permanent middle cerebral artery occlusion (pMCAO). Sprague-Dawley rats were injected with vehicle or 1×10(7) BMMNCs labeled with BrdU via femoral vein 24 h after induction of pMCAO. Functional deficits were assessed weekly through day 42 after pMCAO, and infarct volume was assessed on day 7. We visualized the angioarchitecture by latex perfusion on days 14 and 42. BMMNC transplantation significantly reduced infarct volume and neurologic functional deficits compared with untreated or vehicle-treated ischemic groups. In BMMNC-treated rats, BrdU-positive cells were widely distributed in the infarct boundary zone, were incorporated into vessel walls, and enhanced the growth of leptomeningeal anastomoses, the circle of Willis, and basilar arteries. BMMNCs were shown to differentiate into SMCs and ECs from day 14 after stroke and preserved vascular repair function for at least 6 weeks. Our data indicate that BMMNCs can significantly enhance arteriogenesis and angiogenesis, reduce infarct volume, and promote long-term functional recovery after pMCAO in rats.