Exosomes derived from mesenchymal stem cells as therapeutic agents for Hepatocellular Carcinoma

Abstract

Mesenchymal stem cells (MSCs), the major stem cells for cell therapy, widely exist in most tissues of the body and are easy to obtain. In addition to multi-directional differentiation potential and self-renewal, MSCs also have the characteristics to migrate the injured site and regulate immune responses. Because tumors are considered as "never healing wounds", MSCs have become an ideal carrier for tumor targeted therapy [1]. Exosomes are small vesicles (30-150nm) containing complex lipid, RNAs and proteins. All types of eukaryotic cells can secrete exosomes, and exosomes naturally exist in body fluids, including blood, saliva, urine, cerebrospinal fluid and milk. Exosomes can protect bioactive molecules from extracellular degradation and deliver them to recipient cells in a highly specific manner to exert cell-to-cell communication effect [2]. Similar to exosomes in general, MSCs derived exosomes carry complex cargo, and are therefore well equipped to exert intercellular signal transduction to cope with external pressure. Compared with MSC, the exosomes derived from MSCs have lower immunogenicity and lower risk of tumor formation which make MSCs-exosomes an ideal delivery system for cancer therapy [3, 4]. Hepatocellular carcinoma (HCC) is the sixth common cancer type in the world. And HCC is the fifth most lethal tumor with the characteristics of high malignancy, fast growth, wide metastasis and high recurrence rate. Many studies have proved the effectiveness and safety of MSCs derived exosomes in the treatment of HCC.