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

Abstract

Nowadays, solid organ transplantation (SOT) is an established treatment for patients with end-organ dysfunc-tion, which dramatically improves the quality-of-life. Vascularized composite allotransplants (VCAs) includinghand and face have been reported worldwide over the last 20 years. However, VCAs, differently to SOT, arelife-enhancing instead of life-saving and are not routinely performed due to the risk of immune rejection andthe adverse effects of immunosuppression.Over the past decade, although considerable improvements in short-term outcomes after allotransplantationhave been registered, these results have not been translated into major progress in long-term allograft accep-tance and patient survival. Recently active researches in thefield of biomarker discovery have been conductedto develop individualized therapies for allograft recipients.MicroRNAs (miRNAs) are a small noncoding RNAs functioning as critical regulators of gene and protein expres-sion by RNA interference. They have been connected in numerous biological processes and diseases. Due to theirimmunomodulatory functions, miRNAs have been amended as potential diagnostic and prognostic biomarker forthe detection of rejection in allotransplantation. Due to their specific circulating expression profile, they could actas noninvasive predictive tools for rejection that may help clinicians in an early adjustment of the immunosup-pression protocol during acute rejections episodes. Indeed, specific anti-sense oligonucleotides suppressingmiRNAs expressed in rejection could reduce the rejection rate in allografts and decrease the use ofimmunosuppressants.Wepresent a literaturereviewof the immunomodulatoryproperties and characteristicsofmiRNAs.Wewill sum-marize the current knowledge on miRNAs as potential biomarkers for allograft rejection and possible applicationin allotransplantation monitoring. Finally, we will discuss the advances in preclinical miRNA-based therapies forimmunosuppression