Stem cell
therapy is currently being studied with a view to rescuing various neurological diseases. Such studies require not only the discovery of potent candidate cells but also the development of methods that allow optimal delivery of those candidates to the brain tissues. Given that the blood-brain barrier (BBB) precludes cells from entering the brain, the present study was designed to test whether hyperosmolar
mannitol securely opens the BBB and enhances intra-arterial cell delivery. A noninjured normal canine model in which the BBB was presumed to be closed was used to evaluate the feasibility and safety of the tested protocol. Autologous adipose tissue-derived pericytes with
platelet-derived growth factor receptor β positivity were utilized. Cells were administered 5 min after
mannitol pretreatment using one of following techniques: (1) bolus injection of a concentrated
suspension, (2) continuous infusion of a diluted
suspension, or (3) bolus injection of a concentrated
suspension that had been shaken by repeated syringe pumping. Animals administered a concentrated cell
suspension without
mannitol pretreatment served as a control group. Vital signs, blood parameters, neurologic status, and major artery patency were kept stable throughout the experiment and the 1-month posttreatment period. Although ischemic lesions were noted on magnetic resonance imaging in several mongrel dogs with concentrated cell
suspension, the injection technique using repeated syringe shaking could avert this complication. The cells were detected in both ipsilateral and contralateral cortices and were more frequent at the ipsilateral and frontal locations, whereas very few cells were observed anywhere in the brain when
mannitol was not preinjected. These data suggest that intra-arterial cell infusion with
mannitol pretreatment is a feasible and safe therapeutic approach in stable
brain diseases such as chronic
stroke.