Wharton jelly-derived mesenchymal stem cell exosomes induce apoptosis and suppress EMT signaling in cervical cancer cells as an effective drug carrier system of paclitaxel

Abstract

Mesenchymal stem cells can be obtained and multiplied from various sources and have a very high capacity to release exosomes. Exosomes are nano-sized extracellular vesicles containing biological signaling molecules. This study aimed to determine the effect of MSC-derived exosomes as a drug delivery system for paclitaxel in cervical cancer cells. In this study, human MSC were isolated from wharton jelly of umbilical cord tissue (WJ-MSC), and cells were characterized by CD44, CD90, CD105, and CD34 staining. Exosomes were released in WJ-MSC cells with serum-starved conditions for 48 hours, and particle sizes and structures were examined with zeta-sizer and TEM. In addition, exosomes CD9, CD63, and CD81 markers were checked by western blot. Paclitaxel was loaded into exosomes (Exo-PAC) by electroporation and then incubated with Hela cervical cancer cells for 24 hours. TGF-β, SMAD, Snail, Slug, β-catenin, Notch, Caspase-3, Caspase-9, Bax, Bcl-2 protein and gene expression levels were analyzed in Hela cells. As a result, low concentration Exo-PAC induced apoptosis, and suppressed epithelial-mesenchymal transition proteins in Hela cells. In this study, it has been demonstrated that WJ-MSCs can be used as drug delivery systems for cervical cancer if exosomes are produced scalably in the future.

Potential of Mesenchymal Stromal Cell-Derived Extracellular Vesicles as Natural Nanocarriers: Concise Review

“…Nevertheless, electroporation requires specific equipment and the testing of optimum working conditions before the experiment. This approach has been used for loading EVs with curcumin or paclitaxel [ 58 , 104 ], and for encapsulating siRNAs or miRNAs. Some studies have shown that RNA and EVs can aggregate, resulting in a low loading capacity [ 105 ].…”

On-Chip Organoid Formation to Study CXCR4/CXCL-12 Chemokine Microenvironment Responses for Renal Cancer Drug Testing

“…Caki cells were grown using McCoy’s 5a Medium Modified (Sigma Aldrich, Darmstadt, Germany) medium containing 10% FBS (26140079, Gibco, Waltham, MA, USA), Penicillin-Streptomycin (Sigma) (100 units). Human-derived mesenchymal stem cell (MSC), which we isolated from human umbilical cord tissue in our previous study, characterized and stored in the 3rd passage, was used as the source of mesenchymal stem cells [ 31 ]. MSC cells were grown DMEM/F12 (Gibco, Waltham, MA, USA) supplemented with 15% FBS, Penicillin-Streptomycin (100 units), L-Glutamine, and NaHCO 3 .…”

“…For CXCR4 and CXCL-12 gene expression, cell pellets were kept in RNA lysis buffer in a sonicator for 30 s on ice using our previous study [ 31 ]. Then, total RNA was isolated and purified according to the kit protocol.…”

Mesenchymal stromal/stem cell-derived exosomes and genitourinary cancers: A mini review

“…Exosomes from human umbilical cord Wharton’s jelly MSCs were used in a study to load Paclitaxel and test the exosomes’ effects on cervical cancer (Hela) cell lines. As a consequence, cancer cell death was accelerated by influencing the levels of Bax, BCL2, clv-Cas-3, and clv-Cas-9, and chemoresistance was decreased by affecting epithelial-mesenchymal transition (EMT)-related proteins (such as TGF-β and catenin-β) ( Abas et al, 2022 ).…”