Abstract
Different cell types possess different miRNA expression profiles, and cell/tissue/organ-specific miRNAs (or profiles) indicate different diseases. Circulating miRNA is either actively secreted by living cells or passively released during cell death. Circulating cell/tissue/organ-specific miRNA may serve as a non-invasive biomarker for allo- or xeno-transplantation to monitor organ survival and immune rejection. In this review, we summarize the proof of concept that circulating organ-specific miRNAs serve as non-invasive biomarkers for a wide spectrum of clinical organ-specific manifestations such as liver-related disease, heart-related disease, kidney-related disease, and lung-related disease. Furthermore, we summarize how circulating organ-specific miRNAs may have advantages over conventional methods for monitoring immune rejection in organ transplantation. Finally, we discuss the implications and challenges of applying miRNA to monitor organ survival and immune rejection in allo- or xeno-transplantation.
Highlights
We subsequently review the potential role of circulating miRNAs in organ allo-transplantation, and discuss the challenges that remain if these biomarkers are to prove valuable in organ allo-transplantation
Intracellular levels of miRNAs and/or levels of secretion may fluctuate at different stages of rejection, which may complicate interpretation of the data
Circulating liver-specific miRNA-122 is dramatically up-regulated during liver injury [69,70,71,72,73], but significantly down-regulated during late-stage hepatic cirrhosis [75] and hepatocellular carcinoma [76,77], due to intracellular down-regulation of miRNA production
Summary
Organ failure is the leading cause of human death [1]. Replacing a non-functioning organ with a new one is the most effective strategy to cure terminal organ failure and maintain patients’ lives. Immune rejection still remains a major obstacle for long-term survival of allo- or xeno-transplanted organs (reviewed in [2]). Real-time monitoring of immune rejection is critical for organ allo (xeno)-transplantation. Detection of acute rejection is largely based on clinical data such as a patient’s symptoms and physical signs, and on laboratory data such as biochemical and immunological assays and tissue biopsies [3], some of which are not ideal for clinical application. Biochemical biomarkers of serum creatinine and urine albumin are classical indicators of kidney injury following renal allo (xeno)-transplantation, but are of relatively low sensitivity (reviewed in [7]). Novel non-invasive biomarkers that might monitor immune rejection and/or rejection-associated complications are urgently needed. Circulating miRNAs may serve as non-invasive, specific, sensitive, and low-cost biomarkers in organ allo (xeno)-transplantation
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