Graft vs Host Disease (GvHD)
Graft vs Host Disease (GvHD) presents a spectrum of clinical manifestations, ranging from mild skin rashes to life-threatening multi-organ dysfunction due to allogeneic hematopoietic stem cell transplantation (HSCT), which result in donor T cells mounting an immune response against the host tissues. HSCT remains as one of the most effective therapies for hematologic cancers. However, approximately half of patient population who received HSCT may develop unwanted GvHD complications with 15-30% mortality rate (Dignan et al. 2012). While immunosuppression drugs reduce the chance of graft rejection, effective treatments for GvHD are lacking.
At Invivocue, we support researchers by offering a standard Xenogeneic GvHD model using adult Peripheral Blood Mononuclear Cells (PBMCs) transplanted into immunodeficient mice. This model serves as an invaluable tool for investigating GvHD pathogenesis and testing novel therapeutic interventions.
In this GvHD model, alloreactive T cells from transplanted PBMCs attack allogeneic host tissues and organs in immunodeficient mice and lead to tissue damage and the release of inflammatory cytokines. GvHD symptoms typically appear within 2-3 weeks post PBMC transplantation. A sublethal irradiation before PBMC intravenous injection can further enhance T-cell engraftment efficiency in mice and improve the progression of GvHD.
Experiment Design and Data
Despite the progress made, modelling GvHD remains challenging and requires ongoing refinement to address its multifaceted nature comprehensively. Donor-to-donor variability, particularly in PBMC engraftment rate, GvHD severity, and the consequent therapeutic window, represents the major limitation of GvHD models. To overcome this limitation, we emphasize the importance of donor PBMC selection or the implementation of a contingency plan to facilitate efficacy assessment. Additionally, we offer customized GvHD models designed to meet specific research objectives such as eliminating the need for sublethal irradiation or the application of busulfan-induced myeloablation step before PBMC inoculation. These tailored models address diverse study requirements, ensuring precision and relevance in experimental designs.
Case Study: To evaluate the immunomodulatory properties of Bone Marrow derived MSCs in GvHD model.
These results indicate that GvHD Model can effectively assess T cell and inflammatory responses following human MSC therapy in vivo. Administration of MSCHC demonstrated strong immunosuppressive effects compared to MSCs cultured at low confluency (MSCLC) in this study. These effects could last for 14 days in vivo. The findings of this GvHD study provide valuable insights into an alternative approach for preconditioning MSCs and suggesting that enhancing glycolysis activity could alter the MSCs’ immunosuppressive functions.Read more about other related models and applications
Given the complexity of human disease, in-depth knowledge of each model is key to success in pre-clinical studies. Invivocue offers tailor-made study designs to suit your research needs.