Mesenchymal Stem Cells and Extracellular Vesicles: Therapeutic Potential in Organ Transplantation

Figure 4

Extracellular vesicles as biomarkers in transplantation. There is accumulating evidence showing that EVs play a pivotal role in the immune system. As they are easily detectable in biologic fluids and contain a specific set of nucleic acids, proteins, and lipids reflecting pathophysiologic conditions, differences in EV profiles can be considered as a way to predict, detect, and determine the nature and severity of allograft rejection. (1) Pancreatic islet: After using an anti-HLA antibody, the islet transplant exosome of the recipients’ blood showed significant expression changes in miRNA and the proteome, which enable exosomes to be used to detect rejection before the appearance of hyperglycemia. (2) Heart: Several sensitivity markers (HLA-I, CD2, and SSEA-4 for ACR; ROR1, SSEA-4, HLAII, and CD41b for AMR) can be used for diagnosis and prognosis. Analyzing and combining the different expressions of surface antigens of EV related to the immune system and signal transduction will further improve the diagnostic potential of the inflammatory response, cell survival, and apoptosis. (3) Lung: The expression of molecules such as donor-derived cell-free DNA, cytokines, HIF-1α, and MyD88 in exosomes are isolated from the not stable lung transplant recipients with BOS, which can be predicted and taken adequate measures in advance. Also, the cell-free DNA, long pentraxin-3, angiopoietin-2, and IL-1B are other biomarkers to be used to diagnose and treat inflammatory responses. (4) Renal: bkv-miR-B1-5p and bkv-miR-B1-5p/miR-16 in exosomes are two miRNAs encoded by PVAN that serve as biomarkers of early and late renal transplant dysfunction, and they both exhibit very high discrimination ability for kidney transplant complications.