386 Stereotactic Implantation of Autologous Mesenchymal Stem Cells Improves Neurological Outcomes in a Rat Model of Chronic Middle Cerebral Artery Stroke

Abstract

INTRODUCTION: Limited treatment options exist for patients with chronic infarcts. Multipotent adult mesenchymal stem cells (MSC) show promise as a treatment for chronic stroke. Allogeneic MSCs have been implanted successfully in chronic stroke1,2. However, no literature evaluates the use of autologous MSCs delivered via stereotactic implantation. Autologous MSCs provide safety and accessibility benefits. METHODS: Male Sprague-Dawley rats underwent transient right MCAO for 120 minutes. Brain MRI and sensorimotor behavior were used to evaluate stroke. Sixteen days post stroke, tibial bone marrow was aspirated and MSCs were grown in a closed bioreactor. At 28 days post stroke, 3 trajectories of MSCs were implanted in the peri-infarct zone using a stereotactic robot. The treatments consisted of group 1 (5 x 106 cell dose, N = 6), group 2 (1 x 106 cell dose, N = 6) and a control group (saline injection, N = 9). In a second cohort of animals, Q-dot labeled autologous MSCs were tracked in the brain for 7 or 30 days. RESULTS: Behavior as determined by the modified neurological severity score (0-16) significantly improved in both groups. Stroke volume did not decrease. Histological analysis confirmed increased astrocyte and microglia presence in the affected hemisphere. Quantum dot analysis of injections showed presence of MSCs along trajectory as well as targeting perilesional brain tissue at 7 and 30 days post-implantation. CONCLUSIONS: Stereotactic injection of autologous MSCs represent an effective treatment for chronic stroke. Cells were effective at the lowest dose studied, with no added benefit at higher cell dosages. Unlike allogeneic MSCs which disappear over days to weeks3, autologous MSCs persist long term in the brain, potentially providing continued benefit. This treatment warrants human trials to study its effectiveness.