BMB Reports 2018; 51(11): 545-546  https://doi.org/10.5483/BMBRep.2018.51.11.255
Immune inflammatory modulation as a potential therapeutic strategy of stem cell therapy for ALS and neurodegenerative diseases
Seung Hyun Kim1,2,*, Ki-Wook Oh1,2, Hee Kyung Jin3,5, and Jae-Sung Bae3,4
1Department of Neurology, College of Medicine, Hanyang University, Seoul 04763, Korea, 2Cell Therapy Center for Neurological Disorders, Hanyang University Hospital, Seoul 04763, Korea, 3Stem Cell Neuroplasticity Research Group, Kyungpook National University, Daegu 41566, Korea, 4Department of Physiology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu 41566, Korea, 5Department of Laboratory Animal Medicine, College of Veterinary Medicine, Kyungpook National University, Daegu 41566, Korea
Correspondence to: *Corresponding author. E-mail: kimsh1@hanyang.ac.kr
Received: October 23, 2018; Published online: November 30, 2018.
© Korean Society for Biochemistry and Molecular Biology. All rights reserved.

cc This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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- β 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-β1 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.

Keywords: ALS, Biomarker, BM-MSCs, Immune modulation, Neurodegenerative disease
ACKNOWLEDGEMENTS

This study was supported by the National Research Foundation (NRF) of Korea funded by the Korea Ministry of Science (2018M3C7A1056512). And also supported by the Korea Health Technology R&D Project through the Korea Health Industry, Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI16C2131).

ABBREVIATIONS
ALS: amyotrophic lateral sclerosis
BM-MSCs: bone marrow originated mesenchymal stem cells
CSF: cerebrospinal fluid
Figures
Fig. 1. Summary of plausible mechanisms of intrathecally injected BM-MSCs in ALS.
Fig. 2. Hypothesized mechanisms of repeated intrathecal autologous MSCs therapy for ALS when focused on changes from pre-treated state to post-treated one of key immune-inflammatory cells.


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