Translational Research: May Transplantation of Human Umbilical Cord Blood Mononuclear cells Become an Adjuvant Therapy For Delayed Thrombolysis in Brain Ischemia?

Background: Ischemia stroke is the most common type of stroke. Thrombolysis (rt-PA) is the only approved drug currently available by FDA. Unfortunately, narrow therapeutic time window has limited its effect. Objective: Human umbilical cord blood mononuclear cell (cbMNC) is one of the option treatment for ischemia stroke through their various advantages; availability, pluripotency and immaturity. Patients and Methods/Material and Methods: One group for healthy rat and three groups (n=6 per group) of male wistar rats were undergone permanent middle cerebral artery occlusion (MCAO). Rats were allowed to recover for 7 days before injection of 3x105 human cbMNC. Behavioural tests were performed before MCAO, 1 week after MCAO and at 3,9 and 14 days after cbMNC injection. Infarct area, neurogenesis (GFAP, TUJ1), angiogenesis (VEGF) and human nucleus marker were identified. Results: Behavioral test in sensorimotor evaluation revealed no significant differences between all groups. Spontaneous activity of stroke rats have significantly improved compared to placebo group (pb0.05). Neurogenesis in IA and IV route have better result compare to placebo. Perivascular edema reduced and angiogenesis in IA showed more significant (Pb0.05) compare to IV and placebo respectively. Conclusion: IA and IV human cbMNC implantation provides post stroke functional recovery and spontaneous activity. Human cbMNC as hematopoietic stem cells showed their pluripotency effect.The existence of more neovascularization in periinfarct area and reduced perivascular edema in the administration of cbMNC provides hope for the possibility of blood vessels repair and reducing the occurrence of blood brain barrier leakage and bleeding after delayed thrombolysis when it passes its golden period.