MicroRNAs in solid organ and vascularized composite allotransplantation: Potential biomarkers for diagnosis and therapeutic use

Nowadays, solid organ transplantation (SOT) is an established treatment for patients with end-organ dysfunction, which dramatically improves the quality-of-life. Vascularized composite allotransplants (VCAs) including hand and face have been reported worldwide over the last 20 years. However, VCAs, differently to SOT, are life-enhancing instead of life-saving and are not routinely performed due to the risk of immune rejection and the adverse effects of immunosuppression. Over the past decade, although considerable improvements in short-term outcomes after allotransplantation have been registered, these results have not been translated into major progress in long-term allograft acceptance and patient survival. Recently active researches in the field of biomarker discovery have been conducted to develop individualized therapies for allograft recipients. MicroRNAs (miRNAs) are a small noncoding RNAs functioning as critical regulators of gene and protein expression by RNA interference. They have been connected in numerous biological processes and diseases. Due to their immunomodulatory functions, miRNAs have been amended as potential diagnostic and prognostic biomarker for the detection of rejection in allotransplantation. Due to their specific circulating expression profile, they could act as noninvasive predictive tools for rejection that may help clinicians in an early adjustment of the immunosuppression protocol during acute rejections episodes. Indeed, specific anti-sense oligonucleotides suppressing miRNAs expressed in rejection could reduce the rejection rate in allografts and decrease the use of immunosuppressants. We present a literature review of the immunomodulatory properties and characteristics of miRNAs. We will summarize the current knowledge on miRNAs as potential biomarkers for allograft rejection and possible application in allotransplantation monitoring. Finally, we will discuss the advances in preclinical miRNA-based therapies for immunosuppression. (C) 2020 Elsevier Inc. All rights reserved.