Efficacy of Nanoparticle-based Localised Immunomodulation to Reduce Graft-versus-host Disease in Murine Model of Bone Marrow Transplantation: A Systematic Review

Background and Aim Bone marrow transplantation (BMT), 73.8% of all transplants, is a cornerstone therapy for various haematological disorders. It follows a life-threatening complication; acute graft vs host disease (aGVHD) with 30-60% of incidence. Despite being standard, conventional immunosuppressive therapies are frequently associated with toxicity, infections, and 70% of non-responding patient. A novel, highly targeted nanoparticle-based strategy, while being explored in solid organ transplantation, remains under-investigated in BMT. This systematic review aims to evaluate the efficacy of NP-based strategies to mitigate aGVHD following BMT. Methods A systematic search was conducted using PubMed, Cochrane Library, and Science Direct from April 23, 2001, to August 13, 2024 for propensity-matched studies evaluating efficacy of NP-based therapies in murine models to mitigate GVHD severity. Data were extracted independently by two reviewers. Study quality was assessed using SYRCLE tool. Descriptive analysis was performed as meta-analysis was not possible due to heterogeneity in intervention types. Results Of the 66 studies retrieved, 15 pre-clinical animal studies were selected sample size 2-30/group). Overall, risk of bias was moderate. 12/15 studies reported lower clinical GVHD scores (p< 0.001), 14/15 prevented weight loss (p<0.05), 14/15 prolonged survival with (HR 0.2055, p=0.0112). Histopathological assessments showed decreased tissue damage in the liver (10/11), the intestine (12/12), and the skin (7/7) with p<0.05. 14/15 reported lower levels of inflammatory cytokines (p<0.001). Conclusion NPs therapy has a promising efficacy in mitigating GVHD after BMT. Nevertheless, the heterogeneity of interventions makes generalizability still difficult. It underscores the need for future in-depth translational studies.