Background/Purpose: Cell specific and cytokine targeted therapeutics have underperformed in systemic lupus erythematosus (SLE) in spite of numerous targets examined and clinical trials conducted.  Mesenchymal stem cells (MSCs), especially bone marrow derived MSCs (BMSCs), have emerged as a novel therapy to address the dysregulation in autoimmune diseases because of their immunomodulatory and tissue regeneration properties. Nonetheless, BMSCs have limitations such as heterogeneous cell populations, dysfunction of autologous BMSCs and tumorigenesis. Compared with BMSCs, human gingiva derived MSCs (GMSCs) are superior in regulating immune responses.

Methods: In this study, we prepared gingiva-derived mesenchymal stem cells and adoptively transferred them to NZM2328 mice, a lupus strain that spontaneously develop lupus nephritis with predilection for female mice.

Results: We demonstrate that the adoptively transferred GMSC home to the kidney quickly and have a robust therapeutic effect. Specifically, the administration of GMSCs limits the development of autoantibodies as well as proteinuria, decreases the frequency of plasma cells and lupus nephritis histopathological scores. We further observed that GMSCs directly targeted B cells through suppression of activation and proliferation, plasmocyte differentiation and autoantibody production in an inflammatory milieu.  The blockage of CD39-CD73 pathway dramatically abrogated the suppressive capacities of GMSCs in vitro and in vivo and highlights the significance of this signaling pathway in SLE.

Conclusion: Collectively, manipulation of GMSCs provides a promising strategy for the treatment of patients with SLE and other autoimmune diseases.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/human-gingiva-derived-mesenchymal-stem-cells-are-therapeutic-in-lupus-nephritis-through-targeting-of-cd39-cd73-signaling-pathway/