Local transplantation of adipose-derived stem cells has a significant therapeutic effect in a mouse model of rheumatoid arthritis

• Published in: Scientific reports 2020-02, Vol.10 (1), p.3076-3076, Article 3076
• Main Authors: Ueyama, Hideki, Okano, Tadashi, Orita, Kumi, Mamoto, Kenji, Ii, Masaaki, Sobajima, Satoshi, Iwaguro, Hideki, Nakamura, Hiroaki
• Format: Article
• Language: English
• Subjects: 13/100; 13/2; 13/21; 13/51; 38/77; 631/154/152; 631/532/2074; Adipose Tissue - pathology; Animal models; Animals; Apoptosis; Arthritis, Rheumatoid - pathology; Arthritis, Rheumatoid - therapy; Cartilage (articular); Cartilage, Articular - pathology; Cell Adhesion Molecules - metabolism; Cell migration; Cell Movement; Cell Proliferation; Cytokines; Disease Models, Animal; Female; Fibroblasts; Fibroblasts - metabolism; Fibroblasts - pathology; Glucans; Humanities and Social Sciences; Inflammation; Inflammation - pathology; Macrophages - metabolism; Mice, Inbred BALB C; multidisciplinary; Regeneration; Reverse transcription; Rheumatoid arthritis; Ribonucleic acid; RNA; Science; Science (multidisciplinary); Spheroids; Spheroids, Cellular - metabolism; Spheroids, Cellular - pathology; Stem Cell Transplantation; Stem cells; Synovial Membrane - pathology; Transforming Growth Factor beta1 - metabolism; Transforming growth factor-b1; Up-Regulation
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-60041-2

Adipose-derived stem cells (ADSCs) have anti-inflammatory and regenerative properties. The purpose of this study was to investigate the effect of locally administered ADSCs in a rheumatoid arthritis (RA) mouse model. In an in vivo experiment, single-cell ADSCs and three dimensionally-cultured ADSC spheroids were injected intra-articularly into the knees of RA model mice and histologically assessed. Marked improvement of synovial inflammation and articular cartilage regeneration was found in ADSC-treated mice. Proliferation, migration, and apoptosis assays of synovial fibroblasts incubated with single-cell and spheroid ADSCs were performed. The expression levels of total cytokine RNA in ADSC single cells, spheroids, and ADSC-treated inflammatory synovial fibroblasts were also evaluated by quantitative reverse transcription PCR. ADSCs suppressed the proliferation and migration of activated inflammatory cells and downregulated inflammatory cytokines. TSG-6 and TGFβ1 were significantly upregulated in ADSCs compared to controls and TGFβ1 was significantly upregulated in ADSC spheroids compared to single cells. The apoptosis rate of ADSC spheroids was significantly lower than that of single-cell ADSCs. These results indicated that intra-articular administration of ADSC single cells and spheroids was effective in an RA mouse model, offering a novel approach for the development of effective localized treatments for patients with RA.