World neurosurgery | 2021
Intravenous infusion of mesenchymal stem cells enhances therapeutic efficacy of reperfusion therapy in cerebral ischemia.
Abstract
OBJECTIVE\nReperfusion therapy is a standard therapeutic strategy for acute stroke. Non-favorable outcomes are thought to partially result from impaired microcirculatory flow in ischemic tissue. Intravenous infusion of mesenchymal stem cells (MSCs) reduces stroke volume and improves behavioral function in stroke. One suggested therapeutic mechanism is the restoration of the microvasculature. The goal of this study was to determine whether infused MSCs enhance the therapeutic efficacy of reperfusion therapy following stroke.\n\n\nMETHODS\nFirst, to establish a transient middle cerebral artery occlusion (MCAO) model displaying approximately identical neurological function and lesion volume as seen in permanent MCAO (pMCAO) at day-7 after stroke induction, we transiently occluded the MCA for 90, 110, 120 min. We found that the 110 min-occlusion met these criteria and was used as the transient MCAO (tMCAO) model. Next, four MCAO groups were used to compare the therapeutic efficacy of infused MSCs: (1) pMCAO+vehicle, (2) tMCAO+vehicle, (3) pMCAO+MSC and (4) tMCAO+MSC. Our ischemic model was a unique ischemic model system in which both pMCAO and tMCAO provided similar outcomes during the study period in the groups without MSC infusion groups. Behavioral performance, ischemic volume, and regional cerebral blood flow (rCBF) using arterial spin labeling (ASL)-magnetic resonance imaging and histological evaluation of microvasculature was performed.\n\n\nRESULTS\nThe behavioral function, rCBF, and restoration of microvasculature were greater in group 4 than in group 3. Thus, infused MSCs facilitated the therapeutic efficacy of MCA reperfusion in this model system.\n\n\nCONCLUSIONS\nIntravenous infusion of MSCs may enhance therapeutic efficacy of reperfusion therapy.