Cytokines secreted by mesenchymal stem cells reduce demyelination in an animal model of Charcot-Marie-Tooth disease

Hyeonjin Jeon; Hye Jin Kim; Hyun Myung Doo; Eun Hyuk Chang; Geon Kwak; Won Min Mo; So Young Jang; Myoung Woo Lee; Byung-Ok Choi; Young Bin Hong

doi:10.1016/j.bbrc.2022.01.098

Cytokines secreted by mesenchymal stem cells reduce demyelination in an animal model of Charcot-Marie-Tooth disease

Biochem Biophys Res Commun. 2022 Mar 15:597:1-7. doi: 10.1016/j.bbrc.2022.01.098. Epub 2022 Jan 29.

Authors

Affiliations

¹ Department of Translational Biomedical Sciences, Graduate School of Dong-A University, Busan, South Korea.
² Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, 06351, South Korea.
³ Samsung Biomedical Research Institute, Samsung Advanced Institute of Technology, Samsung Electronics Co, Ltd, Seoul, 06351, South Korea.
⁴ Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 06351, South Korea.
⁵ Department of Biochemistry, College of Medicine, Dong-A University, Busan, 49201, South Korea.
⁶ CELLnLIFE Inc., Seoul, 02455, South Korea.
⁷ Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, 06351, South Korea; Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 06351, South Korea. Electronic address: bochoi77@hanmail.net.
⁸ Department of Translational Biomedical Sciences, Graduate School of Dong-A University, Busan, South Korea; Department of Biochemistry, College of Medicine, Dong-A University, Busan, 49201, South Korea. Electronic address: ybhong@dau.ac.kr.

PMID: 35121177
DOI: 10.1016/j.bbrc.2022.01.098

Abstract

Introduction: Demyelinating Charcot-Marie-Tooth disease (CMT) is caused by mutations in the genes that encode myelinating proteins or their transcription factors. Our study thus sought to assess the therapeutic effects of cytokines secreted from mesenchymal stem cells (MSCs) on this disease.

Methods: The therapeutic potential of Wharton's jelly MSCs (WJ-MSCs) and cytokines secreted by WJ-MSCs was evaluated on Schwann cells (SCs) exhibiting demyelination features, as well as a mouse model of demyelinating CMT.

Results: Co-culture with WJ-MSC protected PMP22-overexpressing SCs from apoptotic cell death. Using a cytokine array, the secretion of growth differentiation factor-15 (GDF-15) and amphiregulin (AREG) was found to be elevated in WJ-MSCs when co-incubated with the PMP22-overexpressing SCs. Administration of both cytokines into trembler-J (Tr-J) mice, an animal model of CMT, significantly enhanced motor nerve conduction velocity compared to the control group. More importantly, this treatment alleviated the demyelinating phenotype of Tr-J mice, as demonstrated by an improvement in the mean diameter and g-ratio of the myelinated axons.

Conclusions: Our findings demonstrated that WJ-MSCs alleviate the demyelinating phenotype of CMT via the secretion of several cytokines. Further elucidation of the underlying mechanisms of GDF-15 and AREG in myelination might provide a robust basis for the development of effective therapies against demyelinating CMT.

Keywords: Charcot-marie-tooth disease (CMT); Cytokine; Mesenchymal stem cell (MSC); Peripheral myelin protein 22 (PMP22).