BackgroundHepatocellular carcinoma (HCC) displays high resistance to conventional chemotherapy. Considering that microRNA-122 (miR-122) performs an essential function to promote chemosensitivity of HCC cells, an effective vehicle-mediated miR-122 delivery may represent a promising strategy for HCC chemotherapy. An increasing interest is focused on the use of exosomes as biological vehicles for microRNAs (miRNA) transfer. Mesenchymal stem cells (MSCs) are known for their capacity to produce large amounts of exosomes. This study aimed to determine whether adipose tissue-derived MSC (AMSC) exosomes can be used for miR-122 delivery.MethodsAMSCs were transfected with a miR-122 expression plasmid. At 48 h after transfection, AMSC-derived exosomes (122-Exo) were harvested and added to recipient HCC cells. Expression levels of miR-122 in AMSCs, exosomes, and HCC cells were quantified by real-time PCR. The mRNA and protein levels of miR-122-target genes in recipient HCC cells were quantified by real-time PCR and Western blot, respectively. The effects of 122-Exo on cell viability, apoptosis, and cell cycle of HCC cells were evaluated by MTT and flow cytometry analysis. Xenograft models were used to determine whether 122-Exo can sensitize HCC cells to sorafenib in vivo.ResultsData showed that miR-122-transfected AMSC can effectively package miR-122 into secreted exosomes, which can mediate miR-122 communication between AMSCs and HCC cells, thereby rendering cancer cells sensitive to chemotherapeutic agents through alteration of miR-122-target gene expression in HCC cells. Moreover, intra-tumor injection of 122-Exo significantly increased the antitumor efficacy of sorafenib on HCC in vivo.ConclusionsThe findings suggest that the export of miR-122 via AMSC exosomes represents a novel strategy to enhance HCC chemosensitivity.

Autoimmune regulator (Aire) is one of the most well-characterized molecules in autoimmunity, but its function outside the immune system is largely unknown. The recent discovery of Aire expression in stem cells and early embryonic cells and its function in the self-renewal of embryonic stem (ES) cells highlight the importance of Aire in these cells. In this study, we present evidence that Aire promotes the expression of the pluripotent factor Lin28 and the self-renewal of ES cells. We presented the first evidence that the let-7 microRNA family contributed to the self-renewal promoting effect of Aire on ES cells. Moreover, we showed that Aire and Lin28 are co-expressed in the genital ridge, oocytes, and cleavage-stage embryos, and the expression level of Lin28 is correlated with the expression level of Aire. Although it is widely considered to be a promiscuous gene expression activator, these results indicated that Aire promotes the self-renewal of ES cells through a specific pathway (i.e., the activation of Lin28 and the inhibition of the let-7 microRNA family). The correlation between Aire and Lin28 expression in germ cells and early embryos indicated an in vivo function for Aire in toti-and pluripotent stem cells. This study presents the first molecular pathway that incorporates Aire into the pluripotency network. Moreover, it presents the first evidence that microRNAs contribute to the regulatory function of Aire and highlights a novel function of Aire in stem cell biology and reproduction. These functions reveal novel perspectives for studying the molecular mechanisms behind the establishment and sustenance of pluripotent identity.

Mesenchymal stromal cells (MSCs) are one of the most intensively studied stem cell types with application aims. However, the molecular characterisation and the relationship between the molecular characterisation and functional properties of MSCs are largely unknown. In this study, we purified the surface proteins from rat bone marrow MSCs (rBMMSCs) and characterised their surface proteome by LC-MS/MS. Moreover, we comparatively analysed the data from this study with the surface proteomics data of mouse and human embryonic stem (ES) cells and human mesenchymal stromal cells (hMSCs). The data showed that, in contrast to ES cells and human mesenchymal stromal cells, rBMMSCs possessed a surface proteomics pattern biased to neural and neural-endocrine lineages, indicating a neural/neural crest bias, and suggested a neural differentiation tendency of these cells. The different surface proteomics pattern between rBMMSCs and hMSCs also suggested that MSCs of different origin might possess a different lineage bias.

From the proteomic analysis, we identified hundreds of novel proteins that have never been characterized for their expression profile and function on human embryonic stem (hES) cells. In this study, we produced a group of monoclonal antibodies against the GRAM domain-containing protein 1A, which was found on hES cells. Using these antibodies, we analyzed the expression of GRAMD1A in various tissues and tumor cell lines. The results showed that GRAMD1A is expressed in the nucleus and cytoplasm of hES cells, cancer cell lines and ectoderm, mesoderm, and endoderm tissues. The development of the monoclonal antibody to GRAMD1A and the characterization of the expression pattern of this protein could have significant implications in the functional characterization of this novel protein.