MESEN

Graft-versus-host disease (GVHD) is an inflammatory disease that happens in Allogeneic transplantation. In GvHD, the donated bone marrow or peripheral blood stem cells view the recipient’s body as foreign, and the donated cells/bone marrow attack the body. This can occur even if the donor and recipient are HLA-identical because the immune system can still recognize other differences between their tissues. It is aptly named graft-versus-host disease because bone-marrow transplantation is the only transplant procedure in which the transplanted cells must accept the body rather than the body accepting the new cells.
There are two forms of GvHD:
  • Acute graft versus host disease (aGvHD): Usually occurs in the first 3 months after transplantation. The major organs involved are the skin, intestine, and liver.
  • Chronic graft versus host disease (cGvHD): It is the major source of late treatment-related complications, although it less often results in death
As an allogeneic transplant recipient, you might experience either form of GvHD, both forms, or neither.
 

MSCs?

Mesenchymal stem cells (MSCs) are multipotent adult stem cells that are present in multiple tissues, including umbilical cord, bone marrow and fat tissue. Mesenchymal stem cells can self-renew by dividing and can differentiate into multiple tissues including bone, cartilage, muscle and fat cells, and connective tissue.
 

MSCs in GvHD

GvHD is mainly caused by cytotoxic reactions of donor lymphocytes in Allogenic transplants, therefore immunosuppression is the cornerstone of aGvHD therapy, with the goal of generating donor/recipient tolerance without removing the graft-versus-leukemia/graft-versus-lymphoma (GVL) impact.
MSCs have shown great promising therapeutic potential towards the suppression of GvHD effects. Due to their immunomodulatory qualities, which have been demonstrated by in vitro research and multiple clinical trials, mesenchymal stem cells (MSCs) are being intensively explored as possible cell therapy agents. In this context, mesenchymal stem cell therapy looks to have a lot of promise, particularly for the treatment of autoimmune and inflammatory disorders also.
Infusion of third-party, HLA-unrelated, or related bone marrow donor MSCs are viable therapy option for aGVHD. Because of their inhibitory effects on the proliferation and cytotoxic activities of immune system cells, MSCs have been employed in the therapy of aGVHD.
MSCs have been shown to interact with other immune system cells like MSCs can interact with natural killer (NK) cells, monocytes, and regulatory T cells principally. Complex methods, such as alterations in antigen-presenting cell maturation and reduction of monocyte-derived dendritic cell (DC) development and activity, are used by these cells to suppress the immune response. MSCs also change the cytokine secretion profiles of effector T cells, DCs, and NK cells, moving them from pro-inflammatory Th1 to anti-inflammatory Th2 cytokine profiles.
The basic properties that underpin MSCs' therapeutic actions for making it a viable choice are as follows:
  • The ability of MSCs to migrate to sites of inflammation when injected intravenously.
  • The ability to differentiate into various cell types.
  • The ability to secrete multiple bioactive molecules capable of inhibiting inflammation and healing injured cells.
  • The ability to perform immunomodulatory functions are currently considered the most important properties of MSCs for potential clinical uses.
Because of their low class I MHC expression and lack of class II MHC molecules, MSCs appear to have minimal immunogenicity. Furthermore, MSCs lack co-stimulatory molecules including CD40, CD80, and CD86, which are implicated in T-cell activation during transplant rejection.
Thus MSCs have shown great potential towards treatment in GvHD and still many clinical trials and studies are under progress to have deep-dive knowledge of these unique types of stem cells.
 
Mesenchymal stem cells: a promising way in therapies of graft-versus-host disease. Cancer Cell Int 20, 114 (2020). https://doi.org/10.1186/s12935-020-01193-z
Clinical Use of Mesenchymal Stromal Cells in the Treatment of Acute Graft-versus-Host Disease. Transfusion Medicine and Hemotherapy 2019;46:27-34. doi: 10.1159/000496809.
https://www.karger.com/Article/Fulltext/496809