Microvesicles Derived from Human Umbilical Cord Wharton’s Jelly Mesenchymal Stem Cells Attenuate Bladder Tumor Cell Growth In Vitro and In Vivo

Abstract

Several studies suggest that mesenchymal stem cells (MSCs) possess antitumor properties; however, the exact mechanisms remain unclear. Recently, microvesicles (MVs) are considered as a novel avenue intercellular communication, which may be a mediator in MSCs-related antitumor effect. In the present study, we evaluated whether MVs derived from human umbilical cord Wharton’s jelly mesenchymal stem cells (hWJMSCs) may inhibit bladder tumor T24 cells growth using cell culture and the BALB/c nu/nu mice xenograft model. CCK-8 assay and Ki-67 immunostaining were performed to estimate cell proliferation in vitro and in vivo. Flow cytometry and TUNEL assay were used to assess cell cycle and apoptosis. To study the conceivable mechanism by which hWJMSC-MVs attenuate bladder tumor T24 cells, we estimated the expression of Akt/p-Akt, p-p53, p21 and cleaved Caspase 3 by Western blot technique after exposing T24 cells to hWJMSC-MVs for 24, 48 and 72h. Our data indicated that hWJMSC-MVs can inhibit T24 cells proliferative viability via cell cycle arrest and induce apoptosis in T24 cells in vitro and in vivo. This study showed that hWJMSC-MVs down-regulated phosphorylation of Akt protein kinase and up-regulated cleaved Caspase 3 during the process of anti-proliferation and pro-apoptosis in T24 cells. These results demonstrate that hWJMSC-MVs play a vital role in hWJMSC-induced antitumor effect and may be a novel tool for cancer therapy as a new mechanism of cell-to-cell communication.

Biological functions of lung cancer cells are suppressed in co‑culture with mesenchymal stem cells isolated from umbilical cord

“…Consistent with the present results, Wu et al (18) demonstrated that microvesicles from human UCMSCs could inhibit the functions of T24 bladder cancer cells. The study also demonstrated that this proliferation suppression was mediated by cell cycle arrest and the induction of apoptosis was mediated by increased expression of caspase 3.…”

Mesenchymal Stromal Cell-Derived Extracellular Vesicles Protect Against Acute Kidney Injury Through Anti-Oxidation by Enhancing Nrf2/ARE Activation in Rats

“…Human foreskin fibroblasts (HFFs) were also obtained from a commercial source (Shanghai Institutes for Biological Sciences) and cultured in RPMI-1640 (Gibco) supplemented with 10% FBS. EVs extraction and characterisation EVs were obtained from hWJMSC and HFF supernatants as previously described [20][21][22]. In brief, cells were cultured in FBS-deprived medium and supplemented with 0.5% bovine serum albumin (BSA, SigmaAldrich, USA) overnight.…”

Extracellular vesicles as regulators of tumor fate: crosstalk among cancer stem cells, tumor cells and mesenchymal stem cells

“…Wharton's jelly MSC-EVs can attenuate the growth of T24 bladder tumor cells in vitro and in vivo by arresting the cell cycle in G 0 /G 1 phase and inducing cell death by apoptosis. Analysis of Akt/ p-Akt by Western blotting revealed that the mechanism involved in the suppression of T24 proliferation is mediated by a reduction in phosphorylation but not in the total expression level of Akt (106). EVs derived from adipose MSCs also had tumor inhibiting effects.…”