Abstract P433: Multipotent Adult Progenitor Cells as a Highly Promising Therapy for Treatment of Intracerebral Hemorrhage

Autor: Robert W. Mays, Annelies Bogaerts, Andrew Goh, Xiurong Zhao, Guanghua Sun, Sean I Savitz, Jaroslaw Aronowski, Sarah A. Busch, Lidiya Obertas, Shun-Ming Ting
Rok vydání: 2021
Předmět:
Zdroj: Stroke. 52
ISSN: 1524-4628
0039-2499
Popis: Background: Multipotent adult progenitor cells (MAPC) are an adherent adult stem cell being evaluated as a treatment for ischemic stroke in humans under the name MultiStem®. However, the efficacy of MAPC cells for the treatment of intracerebral hemorrhage (ICH), the most devastating form of stroke for which there is no effective treatment, is not clear Method: The therapeutic efficacy of MAPC administration was evaluated in both autologous blood injection (ABI) and collagenase (COL) rat ICH models. We treated rats intravenously with 1.2x10 6 cells (sub-optimal dose based on MAPC efficacy in ischemic stroke) and 1.2x10 7 cells (optimal dose) at either 2 or 24h after ICH, and used 2 different doses of collagenase to better understand the dose responses. Outcome measurements included 4 sensorimotor tests (up to 28d), ventricular hypertrophy, spleen size, and body weight (N=128 rats tested across 4 separate experiments). Results: MAPC offered a robust benefit in both ICH models in a dose-dependent fashion. (1) ABI model: at the sub-optimal dose MAPCs had no significant effect on behavioral performance, but effectively reduced ventricular hypertrophy. At an optimal dose, MAPCs at 2h or 24h after ICH, robustly reduced deficits in all 4 behavioral tests, and reduced ventricular hypertrophy by 59% and 35% in 2h and 24h post-treatment groups, respectively. No difference in body weight and spleen size was observed. (2) COL model: MAPC administered 2h after high collagenase dose, reduced hematoma volume (hemispheric hemoglobin level), as measured at 48h after collagenase injection. In addition, MAPC administration significantly reduced neurological deficit in the COL model. Conclusions: MAPC provide a uniquely robust therapeutic effect on clinically relevant neurological and morphological outcomes in two different ICH models. MAPC also reduced bleeding in the COL model, suggesting the potential for MAPC as a safe acute therapeutic treatment after ICH. In addition to having beneficial effects on recovery processes, MAPC could be further evaluated as a candidate to limit the hematoma enlargement during the initial postictal period. We are currently investigating the mechanism of MAPC-induced post-ICH recovery as well as hemostasis using tissue microarray analysis.
Databáze: OpenAIRE
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