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Immune Inflammatory Modulation as a Potential Therapeutic Strategy of Stem Cell Therapy for ALS and Neurodegenerative Diseases
Seung Hyun Kim1, Ki-Wook Oh1, Hee Kyung Jin1, Jae-Sung Bae1,*
1Department of Neurology, College of Medicine, Hanyang University, Seoul, Korea,
2Cell Therapy Center for Neurological Disorders, Hanyang University Hospital, Seoul, Korea,
3Stem Cell Neuroplasticity Research Group and 4Department of Physiology, Cell and Matrix Research Institute, School of Medicine and 5Department of Laboratory Animal Medicine, Kyungpook National University, Daegu, Korea
Abstract
With emerging evidence on the importance of non-cell autonomous toxicity in neurodegenerative diseases, therapeutic strategies targeting modulation of key immune cells. including microglia and Treg cells, have been designed for treatment of ALS and other neurodegenerative diseases. Strategy switching the patient’s environment from a pro-inflammatory toxic to an anti-inflammatory, and neuroprotective condition, could be potential therapy for neurodegenerative diseases. Mesenchymal stem cells (MSCs) regulate innate and adaptive immune cells, through release of soluble factors such as TGF- モ and elevation of regulatory T cells (Tregs) and T helper-2 cells (Th2 cells), would play important roles, in the neuroprotective effect on motor neuronal cell death mechanisms in ALS. Single cycle of repeated intrathecal injections of BM-MSCs demonstrated a clinical benefit lasting at least 6 months, with safety, in ALS patients. Cytokine profiles of CSF provided evidence that BM-MSCs, have a role in switching from pro-inflammatory to anti-inflammatory conditions. Inverse correlation of TGF-モ1 and MCP-1 levels, could be a potential biomarker to responsiveness. Thus, additional cycles of BM-MSC treatment are required, to confirm long-term efficacy and safety.
Abstract, Accepted Manuscript [Submitted on November 6, 2018, Accepted on November 6, 2018]
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