Miaomiao Ye, Tingxian Liu, Liqing Miao, Huihui Ji, Zhihui Xu, Huihui Wang, Jian'an Zhang, Xueqiong Zhu
{"title":"从人绒毛膜间充质干细胞中提取顺铂包裹的 TRAIL 工程外泌体，用于宫颈癌靶向治疗。","authors":"Miaomiao Ye, Tingxian Liu, Liqing Miao, Huihui Ji, Zhihui Xu, Huihui Wang, Jian'an Zhang, Xueqiong Zhu","doi":"10.1186/s13287-024-04006-6","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>Human chorion-derived mesenchymal stem cells (hCD-MSCs) were isolated by adherent culture method. TRAIL-engineered hCD-MSCs (hCD-MSCs<sup>TRAIL</sup>) were constructed by lentivirus transfection, and its secreted Exo (hCD-MSCs-Exo<sup>TRAIL</sup>) were acquired by differential centrifugation and confirmed to overexpress TRAIL by western blotting. Next, nanoscale drug delivery systems (DDP & hCD-MSCs-Exo<sup>TRAIL</sup>) were fabricated by loading DDP into hCD-MSCs-Exo<sup>TRAIL</sup> 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-Exo<sup>TRAIL</sup> in vivo.</p><p><strong>Results: </strong>Compared with hCD-MSCs-Exo, hCD-MSCs-Exo<sup>TRAIL</sup> weakened proliferation and enhanced apoptosis of cervical cancer cells. DDP & hCD-MSCs-Exo<sup>TRAIL</sup> were proved to retard cervical cancer cell proliferation and propel cell apoptosis more effectively than DDP or hCD-MSCs-Exo<sup>TRAIL</sup> alone in vitro. In cervical cancer-bearing mice, DDP & hCD-MSCs-Exo<sup>TRAIL</sup> 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-Exo<sup>TRAIL</sup> showed favorable biosafety in vivo.</p><p><strong>Conclusions: </strong>DDP & hCD-MSCs-Exo<sup>TRAIL</sup> nanoparticles exhibited great promise for cervical cancer treatment as an Exo-based chemo-gene combinational therapy in clinical practice.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"15 1","pages":"396"},"PeriodicalIF":7.1000,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11536590/pdf/","citationCount":"0","resultStr":"{\"title\":\"Cisplatin-encapsulated TRAIL-engineered exosomes from human chorion-derived MSCs for targeted cervical cancer therapy.\",\"authors\":\"Miaomiao Ye, Tingxian Liu, Liqing Miao, Huihui Ji, Zhihui Xu, Huihui Wang, Jian'an Zhang, Xueqiong Zhu\",\"doi\":\"10.1186/s13287-024-04006-6\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>Human chorion-derived mesenchymal stem cells (hCD-MSCs) were isolated by adherent culture method. TRAIL-engineered hCD-MSCs (hCD-MSCs<sup>TRAIL</sup>) were constructed by lentivirus transfection, and its secreted Exo (hCD-MSCs-Exo<sup>TRAIL</sup>) were acquired by differential centrifugation and confirmed to overexpress TRAIL by western blotting. Next, nanoscale drug delivery systems (DDP & hCD-MSCs-Exo<sup>TRAIL</sup>) were fabricated by loading DDP into hCD-MSCs-Exo<sup>TRAIL</sup> 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-Exo<sup>TRAIL</sup> in vivo.</p><p><strong>Results: </strong>Compared with hCD-MSCs-Exo, hCD-MSCs-Exo<sup>TRAIL</sup> weakened proliferation and enhanced apoptosis of cervical cancer cells. DDP & hCD-MSCs-Exo<sup>TRAIL</sup> were proved to retard cervical cancer cell proliferation and propel cell apoptosis more effectively than DDP or hCD-MSCs-Exo<sup>TRAIL</sup> alone in vitro. In cervical cancer-bearing mice, DDP & hCD-MSCs-Exo<sup>TRAIL</sup> 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-Exo<sup>TRAIL</sup> showed favorable biosafety in vivo.</p><p><strong>Conclusions: </strong>DDP & hCD-MSCs-Exo<sup>TRAIL</sup> nanoparticles exhibited great promise for cervical cancer treatment as an Exo-based chemo-gene combinational therapy in clinical practice.</p>\",\"PeriodicalId\":21876,\"journal\":{\"name\":\"Stem Cell Research & Therapy\",\"volume\":\"15 1\",\"pages\":\"396\"},\"PeriodicalIF\":7.1000,\"publicationDate\":\"2024-11-04\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11536590/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Stem Cell Research & Therapy\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s13287-024-04006-6\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CELL & TISSUE ENGINEERING\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Stem Cell Research & Therapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s13287-024-04006-6","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL & TISSUE ENGINEERING","Score":null,"Total":0}
Cisplatin-encapsulated TRAIL-engineered exosomes from human chorion-derived MSCs for targeted cervical cancer therapy.
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.
期刊介绍：
Stem Cell Research & Therapy serves as a leading platform for translational research in stem cell therapies. This international, peer-reviewed journal publishes high-quality open-access research articles, with a focus on basic, translational, and clinical research in stem cell therapeutics and regenerative therapies. Coverage includes animal models and clinical trials. Additionally, the journal offers reviews, viewpoints, commentaries, and reports.
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