Exosomes derived from human umbilical cord mesenchymal stem cells improve myocardial repair via upregulation of Smad7.

It has been previously reported that exosomes derived from human umbilical cord mesenchymal stem cells (hucMSC)­exosomes exhibit cardioprotective effects on the rat acute myocardial infarction (AMI) models and cardiomyocyte hypoxia injury models in vitro, however the exact mechanisms involved require further investigation. The present study aimed to investigate the repair effects of hucMSC­exosomes on myocardial injury via the regulation of mothers against decapentaplegic homolog 7 (Smad7) expression. Compared with sham or normoxia groups (in vivo and in vitro, respectively), western blotting demonstrated that Smad7 expression was significantly decreased in the borderline area of infraction myocardium and in H9C2(2­1) cells following hypoxia­induced injury. Additionally, microRNA (miR)­125b­5p expression was markedly increased using reverse transcription­quantitative polymerase chain reaction, but was reversed by hucMSC­exosomes. Trypan blue staining and lactate dehydrogenase release detection demonstrated that cell injury was significantly increased in the AMI + PBS and hypoxia group compared with in the sham and normoxia groups and was inhibited by hucMSC­exosomes. A dual luciferase reporter gene assay confirmed that Smad7 is a target gene of miR­125b­5p. In addition, miR­125b­5p mimics promoted H9C2(2­1) cell injury following 48 h exposure to hypoxia. Downregulation of Smad7 expression under hypoxia was increased by miR­125b­5p mimics compared with the mimic negative control, and hucMSC­exosomes partially alleviated this phenomenon. In conclusion, hucMSC­exosomes may promote Smad7 expression by inhibiting miR­125b­5p to increase myocardial repair. The present study may provide a potential therapeutic approach to improve myocardial repair following AMI.

Gastric cancer tissue-derived mesenchymal stem cells impact peripheral blood mononuclear cells via disruption of Treg/Th17 balance to promote gastric cancer progression.

Gastric cancer tissue-derived mesenchymal stem cells (GC-MSCs) are important resident stromal cells in the tumor microenvironment (TME) and have been shown to play a key role in gastric cancer progression. Whether GC-MSCs exert a tumor-promoting function by affecting anti-tumor immunity is still unclear. In this study, we used GC-MSC conditioned medium (GC-MSC-CM) to pretreat peripheral blood mononuclear cells (PBMCs) from healthy donors. We found that GC-MSC-CM pretreatment markedly reversed the inhibitory effect of PBMCs on gastric cancer growth in vivo, but did not affect functions of PBMCs on gastric cancer cell proliferation, cell cycle and apoptosis in vitro. PBMCs pretreated with GC-MSC-CM significantly promoted gastric cancer migration and epithelial-mesenchymal transition in vitro and liver metastases in vivo. Flow cytometry analysis showed that GC-MSC-CM pretreatment increased the proportion of Treg cells and reduced that of Th17 cells in PBMCs. CFSE labeling and naïve CD4+ T cells differentiation analysis revealed that GC-MSC-CM disrupted the Treg/Th17 balance in PBMCs by suppressing Th17 cell proliferation and inducing differentiation of Treg cells. Overall, our collective results indicate that GC-MSCs impair the anti-tumor immune response of PBMCs through disruption of Treg/Th17 balance, thus providing new evidence that gastric cancer tissue-derived MSCs contribute to the immunosuppressive TME.

Lefty A protein inhibits TGF-ß1-mediated apoptosis in human renal tubular epithelial cells.

This study aimed to examine the effects of Lefty A protein on transforming growth factor-ß1 (TGF-ß1)-mediated apoptosis in human renal tubular epithelial cells (HK-2). HK-2 cells were transfected with the human Lefty gene to induce the secretion of endogenous Lefty A protein. Following exposure of the HK-2 cells to recombinant human TGF-ß1 (10 ng/ml), p-Smad2/3 protein levels were examined by western blot analysis, and cellular apoptosis was detected by flow cytometry 6, 12, 24 and 48 h following TGF-ß1 treatment. Coculture of renal tubular epithelial cells with TGF-ß1 resulted in a significant increase in p-Smad2/3 protein levels and the rate of cell apoptosis, which were attenuated by liposome-mediated transfection with the Lefty gene. Lefty A protein was able to inhibit the TGF-ß1/Smad signaling pathway and markedly attenuate TGF-ß1-mediated apoptosis in human renal tubular epithelial cells. Taken together, these results indicated that the TGF-ß1/Smad signaling pathway most likely mediates apoptosis in renal tubular epithelial cells. In addition, Lefty A protein is capable of inhibiting the TGF-ß1/Smad pathway to reduce TGF-ß1/Smad-mediated apoptosis in renal tubular epithelial cells. This study may provide novel insights into the prevention and treatment of urinary tract obstruction disease using Lefty A protein.