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Abstract Number: 2290

Umbilical Cord-derived Mesenchymal Stem Cells Suppress Sjogren’s Syndrome Pathology

Yukitomo Hagiwara1, Goh Murayama2, Taiga Kuga2, Yujin Nishioka2, Takumi Saito2, Yu Yamaji2, Tomoko Miyashita2, Makio Kusaoi3, Ken Yamaji2 and Naoto Tamura2, 1Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan, 2Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine, Tokyo, Japan, 3Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine, Bunkyo, Tokyo, Japan

Meeting: ACR Convergence 2024

Keywords: B-Lymphocyte, Mesenchymal stem cells, Monocytes/macrophages, Sjögren's syndrome, T Cell

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Session Information

Date: Monday, November 18, 2024

Title: Sjögren's Syndrome – Basic & Clinical Science Poster II

Session Type: Poster Session C

Session Time: 10:30AM-12:30PM

Background/Purpose: Primary Sjögren’s syndrome (pSS) is characterized by lymphocytic infiltration of the salivary and lacrimal glands, leading to functional loss and gradually causing dry mouth and dry eyes. Recent studies have suggested that mesenchymal stem cell (MSC) transplantation may improve salivary function and reduce lymphocytic infiltration of the salivary glands. This study aimed to confirm the anti-inflammatory effects of umbilical cord-derived mesenchymal stem cells (MSC) on pSS pathology and elucidate the underlying mechanisms.

Methods: Peripheral blood mononuclear cells (PBMC) from pSS patients were co-cultured with MSCs under various stimulatory conditions to evaluate the inhibition of cell differentiation and cytokine production. CD4+ T cells and B cells were isolated from the peripheral blood of pSS patients and co-cultured with MSCs stimulated with CpG-ODN or pSS-associated autoantigens. The changes in cell subsets and the suppression of IgG production due to MSC inhibitory effects were evaluated.

Results: When PBMCs were co-cultured with MSCs in the presence of anti-CD3/CD28 antibodies, the proportion of IFN-γ and IL-4 producing T cells decreased compared to cultures without MSCs. Additionally, when PBMCs were co-cultured with MSCs in the presence of Imiquimod, the proportion of TNF-α producing monocytes decreased compared to cultures without MSCs. Co-culturing CD4+ T cells and B cells from pSS patients with MSCs in the presence of CpG-ODN significantly reduced the proportion of plasma cells compared to B cell monocultures. Furthermore when CD4⁺T cells and B cells were co-cultured in the presence of pSS-associated autoantigen, IgG production was suppressed with MSCs compared to without MSCs.

Conclusion: In the presence of MSCs, TNF-α and IFN-γ production from T cells and monocytes was shown to be suppressed, with reduced differentiation into plasma cells and IgG production to pSS-associated autoantigens. In pSS patients, TNF-α and IFN-γ are known to increase the expression of Fas and FasL on salivary gland epithelial cells, and B cells induce apoptosis of salivary gland epithelial cells via cell-cell contact. The anti-inflammatory effects of MSCs may potentially improve the dry eyes and dry mouth with pSS.

Supporting image 1

When PBMCs were co-cultured with MSCs in the presence of anti-CD3/CD28 antibodies, the proportion of IFN-γ and IL-4 producing T cells decreased compared to cultures without MSCs.

Supporting image 2

When PBMCs were co-cultured with MSCs in the presence of Imiquimod, the proportion of TNF-α producing monocytes decreased compared to cultures without MSCs.


Disclosures: Y. Hagiwara: Cell Exosome Therapeutics Inc., 5; G. Murayama: Asahi Kasei Medical Company Limited, 5, Cell Exosome Therapeutics Inc., 5; T. Kuga: None; Y. Nishioka: None; T. Saito: Asahi Kasei Medical Company Limited, 5; Y. Yamaji: None; T. Miyashita: None; M. Kusaoi: Asahi Kasei Medical Company Limited, 5, Cell Exosome Therapeutics Inc., 5; K. Yamaji: Asahi Kasei Medical Company Limited, 5; N. Tamura: AbbVie/Abbott, 6, Asahikasei, 5, AstraZeneca, 6, Ayumi, 5, Bristol-Myers Squibb(BMS), 5, 6, Cell Exosome Therapeutics, 5, Chugai, 6, Esai, 6, GlaxoSmithKlein(GSK), 2, 5, Janssen, 6, Japan Boehringer-Ingelheim, 6, Japan Eli Lilly, 5, Novartis, 2, 6, Taisyo, 6, Tanabe Mitsubishi, 6.

To cite this abstract in AMA style:

Hagiwara Y, Murayama G, Kuga T, Nishioka Y, Saito T, Yamaji Y, Miyashita T, Kusaoi M, Yamaji K, Tamura N. Umbilical Cord-derived Mesenchymal Stem Cells Suppress Sjogren’s Syndrome Pathology [abstract]. Arthritis Rheumatol. 2024; 76 (suppl 9). https://acrabstracts.org/abstract/umbilical-cord-derived-mesenchymal-stem-cells-suppress-sjogrens-syndrome-pathology/. Accessed .
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