Human GMSCs Treat Murine Model with Aplastic Anemia Through Regulating the Balance between Treg and Th17 Cells

Abstract

Severe aplastic anemia (AA) is a rare autoimmune disease characterized by severe pancytopenia and bone marrow failure. The recent finding of an abnormal quantity and function of T helper (Th) and regulatory T (Treg) cells in peripheral blood of patients has emerged as the major cause of the condition. Accumulating evidence has revealed that human gingiva-derived mesenchymal stem cells (GMSCs) are emerging as a new line of mesenchymal stem cells may have the potential to control or even treat autoimmune diseases through correcting the balance between Th and Treg cells. Given that GMSCs have a robust immune regulatory function and regenerative ability, we investigated the effect of GMSCs on preventing T cell-mediated bone marrow failure (BMF) in an AA mouse model. We observed that infusion of GMSCs markedly attenuated histological BM damage, controlled immunologically-mediated disorders in AA mice, significantly improved AA mice survival by significantly reducing cell infiltration of both CD8 cells and CD4 T cells (including Th1 and Th17 cells) in lymph nodes and decreased pro-inflammatory cytokines levels in lymph nodes and plasma. Moreover, GMSCs up-regulated the levels of Tregs and increased Foxp3 expression in lymph nodes. Our results demonstrate that the predominant Th1 and Th17 cell infiltration in the AA model could be significantly reduced while Treg cells are increased by GMSCs treatment. Collectively, our data demonstrate that GMSCs can attenuate T cell-mediated bone marrow failure through targeting the balance of Th17 and Treg cells, implicating that the use of GMSCs many have potential clinical application in prevention and treatment of patients with AA. Funding Statement: This study was supported by the National Key R&D Program of China (2017YFA0105800), the National Natural Science Foundation of China (No. 81671611), the Program for Guangdong Introducing Innovative and Entrepreneurial Teams (2016ZT06S252), the National Natural Science Foundation of Guangdong Province (No. 2014A030313131) and NIH R61 AR073409. Declaration of Interests: All authors have no conflict of interest. Ethics Approval Statement: This study was carried out in accordance with the recommendations of the animal use protocol, which was approved by the Institutional Animal Care and Use Committee of Sun Yat-Sen University (Approve number: [2018]02-195-01). Human gingiva samples were collected following routine dental procedures at the Division of Dentistry in the Third Hospital at the Sun Yat-sen University, which were approved by the medical ethics committees of Institutional Review Boards (IRB) at the Third Hospital at the Sun Yat-sen University.