Safety and Efficacy of Intraventricular Delivery of Bone Marrow-Derived Mesenchymal Stem Cells in Hemorrhagic Stroke Model

Abstract

External ventricular drain (EVD) is used clinically to relieve intracranial pressure and occasionally to deliver medications following intracerebral hemorrhage (ICH). Mesenchymal stem cell (MSC) therapy has been shown to be neuroprotective and can induce neuroregeneration in stroke models. We evaluated the safety and efficacy of delivering MSCs intraventricularly in a rat hemorrhagic stroke model. Using autologous blood, hemorrhagic stroke was induced at specific coordinates in the right basal ganglia. After 30 minutes, rats were treated with either bone marrow-derived MSCs or a phosphate-buffered saline placebo via direct intraventricular infusion. Three dosages (2 × 10 5 /kg, 5 × 10 5 /kg, and 1 × 10 6 /kg) of MSCs were administered. Forelimb use asymmetry test was employed to evaluate functional improvement after cell therapy. At the end of the experiment, peripheral blood samples and organs were harvested; biochemistry, cytokine, and growth factor analysis and histology evaluations were performed to explore cell toxicity and cell fate, and the effects of MSC therapy on injury volume, anti-inflammation, and neurogenesis. Intraventricular administration of MSCs in ICH rat model showed improved behavior and alleviated brain damage. Additionally, treated ICH rats showed significantly reduced expression of IL-1α, IL-6, and IFN-γ. No obvious cell toxicity was noticed through blood chemistry and histology evaluation. None of the infused MSCs were detected at the end of the experiment. EVD is safe and effective to use as a method of delivering MSCs to treat ICH. Intraventricularly delivered MSCs have anti-inflammatory properties and a capacity to induce neurogenesis and improve function following ICH injury.