Abstract 85: Intravenous Application of Autologous Preconditioned Mesenchymal Stem Cells for Ischemic Stroke: Final Results of a Randomized Controlled Trial

Abstract

Background: Preclinical studies showed that stroke induces a process of recovery via the activation of MSCs, and culture methods for MSCs using stroke patient’s serum obtained during the acute phase of a stroke could constitute a novel MSC activation method. The present trial was conducted to test whether modified MSCs with autologous serum improve the recovery in patients with chronic stroke. Methods: In this prospective, randomized controlled trial, patients with moderate-to-severe disabling middle cerebral artery territory infarct observed within 90 days of the onset of symptoms were assigned, in a 2:1 ratio, to receive MSC therapy (intervention group) or standard care alone (control group), and followed for 3 months. The primary outcome was the score on the mRS at 3 months of treatment. Results: Totals of 39 and 15 patients completed the follow-up in the intervention and control groups, respectively. The mean interval between stroke onset to randomization was 20.2±17.2 days. The mean age was 63.4±13.9 and median NIHSS score was 11 [IQR, 8-17] in the study population. The baseline characteristics were well balanced in the two groups. The median mRS score at day 90 was 3 [IQR, 3-4] in the intervention group and 4 [IQR, 3-4] in the treatment group (P = 0.879). Proportional odds ratio for good functional outcome (mRS at 3 months of treatment) with the stem cell treatment was 0.65 (95% confidence interval, 0.18-2.44; P = 0.529), after adjusting for age, gender, and initial NIHSS scores. In secondary efficacy endpoint, no significant difference was found in the two groups measured by global Fugl-Meyer assessment. However, Fugl-Meyer score in the lower motor function showed significant improvement in the intervention group (delta between baseline and 90-day, 2.3 vs. 4.7; P<0.01). In terms of secondary safety outcomes, one patient in the control group experienced recurrent stroke, and one each patients of the intervention group had transient allergic reaction and one pneumonia. Conclusions: Among patients with chronic stroke, treatment with autologous preconditioned MSC was feasible but did not improve long-term functional outcome. Further studies are needed to select responders to MSC therapies and to improve efficacy of stem cell therapeutics.