LC-MS/MS-based serum proteomics reveals a distinctive signature in a rheumatoid arthritis mouse model after treatment with mesenchymal stem cells

Namhee Jung; Soyoung Park; TaeHo Kong; Hwanhee Park; Woo Min Seo; Seunghee Lee; Kyung-Sun Kang

doi:10.1371/journal.pone.0277218

LC-MS/MS-based serum proteomics reveals a distinctive signature in a rheumatoid arthritis mouse model after treatment with mesenchymal stem cells

PLoS One. 2022 Nov 4;17(11):e0277218. doi: 10.1371/journal.pone.0277218. eCollection 2022.

Authors

Namhee Jung¹, Soyoung Park¹, TaeHo Kong¹, Hwanhee Park¹, Woo Min Seo¹, Seunghee Lee¹, Kyung-Sun Kang^{1

2

3}

Affiliations

¹ Stem Cell and Regenerative Bioengineering Institute, Global R&D Center, Kangstem Biotech Co., Ltd., Geumcheon-gu, Seoul, South Korea.
² Adult Stem Cell Research Center, College of Veterinary Medicine, Seoul National University, Seoul, South Korea.
³ Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, South Korea.

Abstract

Mesenchymal stem cells (MSCs) are known to be able to modulate immune responses, possess tissue-protective properties, and exhibit healing capacities with therapeutic potential for various diseases. The ability of MSCs to secrete various cytokines and growth factors provides new insights into autoimmune-diseases such as rheumatoid arthritis (RA). RA is a systemic autoimmune disease that affects the lining of synovial joints, causing stiffness, pain, inflammation, and joint erosion. In recent years, MSCs-based therapies have been widely proposed as promising therapies in the treatment of RA. However, the mechanism involved in disease-specific therapeutic effects of MSCs on RA remains unclear. To clarify the mechanism involved in effects of MSCs on RA, proteomic profiling was performed using an RA mouse model before and after treatment with MSCs. In this study, treatment efficacy of human umbilical cord blood-mesenchymal stem cells (hUCB-MSCs) was confirmed using a type II collagen-induced arthritis (CIA) mouse model. Results of measuring incidence rates of arthritis and clinical arthritis index (CAI) revealed that mice administrated with hUCB-MSCs had a significant reduction in arthritis severity. Proteins that might affect disease progression and therapeutic efficacy of hUCB-MSC were identified through LC-MS/MS analysis using serum samples. In addition, L-1000 analysis was performed for hUCB-MSC culture medium. To analysis data obtained from LC-MS/MS and L-1000, tools such as ExDEGA, MEV, and DAVID GO were used. Results showed that various factors secreted from hUCB-MSCs might play roles in therapeutic effects of MSCs on RA, with platelet activation possibly playing a pivotal role. Results of this study also suggest that SERPINE1 and THBS1 among substances secreted by hUCB-MSC might be key factors that can inhibit platelet activation. This paper is expected to improve our understanding of mechanisms involved in treatment effects of stem cells on rheumatoid arthritis.

Copyright: © 2022 Jung et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Arthritis, Rheumatoid*
Chromatography, Liquid
Disease Models, Animal
Humans
Mesenchymal Stem Cell Transplantation*
Mesenchymal Stem Cells*
Mice
Proteomics
Tandem Mass Spectrometry

Grants and funding

This study was supported by the Korea Health Industry Development Institute (KHIDI), Ministry of Health and Welfare (HI20C0675), Republic of Korea. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.