INTRA-ARTERIAL ADMINISTRATION OF HUMAN DENTAL PULP STEM CELLS PROMOTES NEUROVASCULAR REPAIR AND FUNCTIONAL RECOVERY AFTER ISCHEMIC STROKE

Ischemic stroke induces extensive neurovascular damage characterized by blood–brain barrier (BBB) disruption, vascular degeneration, and sustained neuroinflammation, leading to functional deficits. Although reperfusion therapies restore cerebral blood flow, strategies to promote vascular repair and modulate post-ischemic inflammation remain limited. Human Dental Pulp Stem Cells (hDPSCs) are an accessible stem cell source with pro-angiogenic and immunomodulatory properties, making them promising candidates for neurovascular repair. Here, we investigated the effects of intra-arterial administration of hDPSCs in a rat model of stroke. Sprague–Dawley rats were subjected to 75 minutes of middle cerebral artery occlusion (MCAO) and received intracarotid injections of hDPSCs one hour after occlusion. Neurological function was assessed longitudinally, and animals were analyzed 14 days post-MCAO. Histological analyses confirmed the presence of grafted hDPSCs within infarct core and peri-infarct regions. Immunohistochemical analyses using human-specific markers (STEM121 and hCD31) revealed that grafted hDPSCs were associated with lectin-positive vascular structures, suggesting their contribution to perfused vascular networks. hDPSC-treated animals exhibited significantly improved neurological recovery, accompanied by reduced infarct volume as assessed by Cresyl Violet staining. Assessment of BBB integrity using Evans Blue extravasation revealed reduced vascular leakage in hDPSC-treated animals. Furthermore, analysis of the inflammatory response revealed a reduction of CD11b⁺ cells within the infarcted tissue of hDPSC-treated animals, indicating attenuation of post-ischemic neuroinflammation. Analyses of endogenous neurogenesis and neural progenitor recruitment are ongoing.
Together, these findings demonstrate that intra-arterial delivery of hDPSCs promotes functional recovery after ischemia through a combination of vascular repair, BBB stabilization, and modulation of the inflammatory response.