-Original-

Human Adipose Tissue-Derived Stem Cells Inhibit Coronary Artery Vasculitis in a Mouse Model of Kawasaki Disease

Ryohei Fukunaga¹, Takahiro Ueda¹, Ryosuke Matsui¹, Toshikazu Itabashi¹, Ryuji Fukazawa¹, Noriko Nagi-Miura² and Yasuhiko Itoh¹

¹Department of Pediatrics, Nippon Medical School, Tokyo, Japan
²Laboratory for Immunopharmacology of Microbial Products, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan

Background: Adipose tissue-derived mesenchymal stem cells (ADSCs) are used for the treatment of various diseases because of their rapid proliferation and high anti-inflammatory and tissue repair properties. Kawasaki disease is a systemic vasculitis with coronary arteritis and aneurysms occurring in pediatric patients. In this study, we examined serologically and pathologically whether the administration of human ADSCs (hADSCs) to a mouse model of Kawasaki disease could suppress vasculitis.
Methods: Candida albicans water-soluble fractions were intraperitoneally injected into DBA/2 mice for 5 consecutive days to generate a mouse model of Kawasaki disease. The model mice were intravenously administered hADSCs or phosphate-buffered saline (PBS). Serum samples collected on days 15 and 29 were used to compare cytokine levels. Mouse hearts dissected on day 29 were subjected to hematoxylin and eosin and immunohistological staining using Galectin-1 (Gal-1), a protein involved in cardiovascular homeostasis, and CD44, a cell-surface marker of hADSCs.
Results: Comparison of inflammation-related cytokines showed a significant decrease in IL-1α expression at day 15 (P<0.05) and IL-6 expression at day 29 (P<0.01) in the hADSCs-treated group compared to the PBS group. Evaluation by hematoxylin and eosin staining showed decreased inflammatory cell infiltration and a tendency towards increased Gal-1 expression in the hADSCs group. CD44 expression was not observed in both the groups. The survival curve showed that the hADSCs group had a significantly longer survival time (P<0.05).
Conclusions: The present experimental results indicate that hADSCs have an early anti-inflammatory effect, and that Gal-1 may be involved in preventing inflammation and reducing tissue damage.

J Nippon Med Sch 2024; 91: 218-226

Keywords
Adipose tissue, mesenchymal stem cells, cytokines, Gal-1, Kawasaki disease

Correspondence to
Takahiro Ueda, MD, PhD, Department of Pediatrics, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan
yuri878t@nms.ac.jp

Received, September 16, 2023
Accepted, November 22, 2023