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| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Ye, Miaomiao Liu, Tingxian Miao, Liqing Ji, Huihui Xu, Zhihui Wang, Huihui Zhang, Jian’an Zhu, Xueqiong |
| Abstract | Background Cisplatin (DDP) is an efficacious and widely applied chemotherapeutic drug for cervical cancer patients who are diagnosed as metastatic and inoperable, or desiring fertility preservation. Tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL) selectively triggers cancer cells apoptosis by binding to cognate death receptors (DR4 and DR5). Mesenchymal stem cells-derived exosomes (MSCs-Exo) have been regarded as ideal drug carriers on account of their nanoscale, low toxicity, low immunogenicity, high stability, biodegradability, and abundant sources. Methods Human chorion-derived mesenchymal stem cells (hCD-MSCs) were isolated by adherent culture method. TRAIL-engineered hCD-MSCs (hCD-MSCsTRAIL) were constructed by lentivirus transfection, and its secreted Exo (hCD-MSCs-ExoTRAIL) were acquired by differential centrifugation and confirmed to overexpress TRAIL by western blotting. Next, nanoscale drug delivery systems (DDP & hCD-MSCs-ExoTRAIL) were fabricated by loading DDP into hCD-MSCs-ExoTRAIL via electroporation. The CCK-8 assay and flow cytometry were conducted to explore the proliferation and apoptosis of cervical cancer cells (SiHa and HeLa), respectively. Cervical cancer-bearing nude mice were constructed to examine the antitumor activity and biosafety of DDP & hCD-MSCs-ExoTRAIL in vivo. Results Compared with hCD-MSCs-Exo, hCD-MSCs-ExoTRAIL weakened proliferation and enhanced apoptosis of cervical cancer cells. DDP & hCD-MSCs-ExoTRAIL were proved to retard cervical cancer cell proliferation and propel cell apoptosis more effectively than DDP or hCD-MSCs-ExoTRAIL alone in vitro. In cervical cancer-bearing mice, DDP & hCD-MSCs-ExoTRAIL evidently hampered tumor growth, and its role in inducing apoptosis was mechanistically associated with JNK/p-c-Jun activation and survivin suppression. Moreover, DDP & hCD-MSCs-ExoTRAIL showed favorable biosafety in vivo. Conclusions DDP & hCD-MSCs-ExoTRAIL nanoparticles exhibited great promise for cervical cancer treatment as an Exo-based chemo-gene combinational therapy in clinical practice. Graphical abstract |
| Related Links | https://stemcellres.biomedcentral.com/counter/pdf/10.1186/s13287-024-04006-6.pdf |
| Ending Page | 17 |
| Page Count | 17 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| ISSN | 17576512 |
| DOI | 10.1186/s13287-024-04006-6 |
| Journal | Stem Cell Research & Therapy |
| Issue Number | 1 |
| Volume Number | 15 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2024-11-04 |
| Access Restriction | Open |
| Subject Keyword | Stem Cells Cell Biology Regenerative Medicine Tissue Engineering Biomedical Engineering and Bioengineering Exosomes TRAIL Cisplatin Nanoscale drug delivery systems Cervical cancer Regenerative Medicine/Tissue Engineering |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Medicine Biochemistry, Genetics and Molecular Biology Molecular Medicine |
| Journal Impact Factor | 7.1/2023 |
| 5-Year Journal Impact Factor | 7.9/2023 |
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