A comparative study of different doses of bone marrow-derived mesenchymal stem cells improve post-stroke neurological outcomes via intravenous transplantation

Abstract

BackgroundIschemic stroke treatments are intriguing and somewhat controversial. Recent findings have shown that human mesenchymal stem cells (MSC) may have therapeutic potential in ischemic stroke. Our hypothesis was that MSC therapy would promote sensory and motor recovery. Therefore, we intended to explore the optimal transplantation dose of MSC. MethodsAdult Sprague-Dawley (SD) rats were induced to undergo transient focal cerebral ischemia by occluding the middle cerebral artery. A series of standard neurological/neurobehavioral experiments, including Neurological Severity Score (NSS) assessment, corner turning test, von Frey test, and rotarod were then performed on post stroke rats following treatment with vehicle or different doses of MSC (1 × 106, 2 × 106, and 5 × 106) through tail vein. To figure out the time course of neurological and functional recovery following ischemic stroke, tests were administered at regular intervals (days 1, 3, 7, 14, 21, and 28) after reperfusion. And the cerebral infarction volume was measured and analyzed by multi-slices H&E staining and micro-PET / CT in all of the groups at day 35 after ischemia stroke. Activation of microglia was explored by immunofluorescence at day 35 after ischemia stroke. ResultsThe sensory and motor function was significantly improved by MSC treatment in stroke rats, along with cerebral infarction volume reduction. Besides, different doses of MSC have more or less reflected the therapeutic effect on stroke. The prominent treatment outcome in neurobehavioral recovery and infarction reduction was shown in low dose group with an injection dose of 1 × 106 cells. Nevertheless, the medium and high dose MSC could inhibit the activation of microglia much stronger. ConclusionsTreatment with MSC restored the sensory and motor function of cerebral ischemia rats, indicating it may be an effective therapy for ischemic stroke.