Cell Therapy: A New Technology for Cerebral Circulation Restoration after Ischemia/Reperfusion.

Abstract

Cell therapy with mesenchymal stem cells (MSCs) may be a promising technique for cerebral blood flow restoration after transient ischemia. Before a practical application of the cell material, 7-9 days are required for its cultivation. We studied the efficacy of human MSC (hMSC) transplantation performed 7 days after cerebral ischemia/reperfusion (I/R) to help recover cerebral circulation. The intravital micrograph technique was used to comparatively evaluate the vasculature density in the pia mater and the reactivity of the pial arteries in response to acetylcholine (ACh) in rats after I/R (clamping of both carotid arteries and a simultaneous decrease in and strict maintenance of the mean BP at 45 ± 2 mm Hg for 12 min) and with/without hMSC transplantation. Perfusion (P) in the sensorimotor cortex was assessed using laser dopplerography. After 14 and 21 days, the vasculature density in I/R-affected rats was 1.2- to 1.4-fold and 1.2- to 1.3-fold lower, respectively, than that in the controls. The number of ACh-dilated arteries decreased 1.6- to 1.9-fold and 1.2- to 1.7-fold 14 and 21 days after I/R, respectively. After 21 days, the P level decreased 1.6-fold, on average. Administration of hMSCs on day 7 after I/R resulted in complete recovery of the vasculature density by day 14. ACh-mediated dilatation fully recovered only in arteries of less than 40 μm in diameter within 21 days. After 21 days, the P level was 1.2-fold lower than that in the controls but significantly higher than that in rats after I/R without hMSCs. Delayed administration of MSCs after a transient cerebral ischemic attack affords the time for the procedures required to prepare cell material for transplantation and provides a good therapeutic response in the pial microvasculature.