Breaking the graft-versus-host-disease barrier: Mesenchymal stromal/stem cells as precision healers

AbstractMesenchymal Stromal/Stem Cells (MSCs) are multipotent, non-hematopoietic progenitor cells with a wide range of immune modulation and regenerative potential which qualify them as a potential component of cell-based therapy for various autoimmune/chronic inflammatory ailments. Their immunomodulatory properties include the secretion of immunosuppressive cytokines, the ability to suppress T-cell activation and differentiation, and the induction of regulatory T-cells. Considering this and our interest, we here discuss the significance of MSC for the management of Graft-versus-Host-Disease (GvHD), one of the autoimmune manifestations in human. In pre-clinical models, MSCs have been shown to reduce the severity of GvHD symptoms, including skin and gut damage, which are the most common and debilitating manifestations of this disease. While initial clinical studies of MSCs in GvHD cases were promising, the results were variable in randomized studies. So, further studies are warranted to fully understand their potential benefits, safety profile, and optimal dosing regimens. Owing to these inevitable issues, here we discuss various mechanisms, and how MSCs can be employed in managing GvHD, as a cellular therapeutic approach for this disease.Preconditioning of MSCs before infusing in patients with GvHDPreconditioning of MSCs is indeed a crucial step in improving the effectiveness of stem cell therapy for GvHD. Preconditioning involves exposing MSCs to cytokines, growth factors, and/or drugs prior to transplantation. This exposure induces changes in the MSCs' behavior such as enhance the anti-inflammatory and immunomodulatory properties of MSCs, which can reduce the severity of GvHD and improving the homing of MSCs to the injured target organ helping in tissue repair. Overall, precondition makes MSCs more effective in combating GvHD.Keywords: Apoptosisefferocytosisgraft-versus-host-diseaseimmunomodulationmesenchymal stromal cellssecretome AcknowledgmentFigures are created using Biorender.com.Additional informationFundingThe study was supported by the Indian Council of Medical Research, New Delhi, India (Grant ID: 2021/14763 and 2021/13853) and the Science and Engineering Board, New Delhi, India (Grant Id: EMR/2016/002633).