Conserved mechanisms underlying benefit of MultiStem® cell therapy for neurological injury and disease Maya I. Camhi, Sarah A. Busch, Robert W. Mays Athersys, Inc., Cleveland, OH USA
Over the past twenty years, off-the-shelf cellular therapies have steadily progressed through pre-clinical and clinical development for the treatment of neurological disease and injury. However, a full understanding of the mechanism of benefit is necessary to optimize therapeutic efficacy. Athersys is developing MultiStem®, a unique bone marrow-derived allogeneic cell therapy based upon the proprietary MAPC® cell technology, for the treatment of multiple neurological, cardiac, and inflammatory indications. Recently, Athersys and collaborators have performed focused pre-clinical animal studies to evaluate the potential of a conserved cell-mediated mechanism of benefit. Based on these studies, we hypothesize that MAPC cell infusion alters the innate immune response directly via interactions with splenocytes. Detailed biodistribution studies have revealed that MAPC cells home primarily to the spleen, reside in the marginal zone, and likely interact with splenocytes. MAPC cell treatment reduces both systemic-inflammation and neuro-inflammation, as demonstrated by a reduction of pro-inflammatory gene expression, circulating cytokines, and monocyte/macrophage-mediated exacerbation of the initial injury. We have observed a consistent Th2 response following MAPC cell infusion, consisting of increased T regulatory cells and “alternatively” activated macrophage/microglial phenotype. Further, delivery of 1.2 billion MultiStem cells intravenously 24-36 hours following human ischemic stroke onset in a phase 2 clinical trial provided sustained significant functional improvements at 1 year. Our studies suggest that these cells modulate the peripheral immune response resulting in neuroprotection and allowing for the potential of long term neurological recovery in a number of serious injury and disease indications.
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