Giulia Grisendi, Massimiliano Dall'Ora, Giulia Casari, Giliola Spattini, Moein Farshchian, Aurora Melandri, Valentina Masicale, Fabio Lepore, Federico Banchelli, Riccardo Cuoghi Costantini, Angela D'Esposito, Chiara Chiavelli, Carlotta Spano, Andrea Spallanzani, Tiziana Petrachi, Elena Veronesi, Manuela Ferracin, Roberta Roncarati, Jonathan Vinet, Paolo Magistri, Barbara Catellani, Olivia Candini, Caterina Marra, Albino Eccher, Luca Reggiani Bonetti, Edwin M Horwtiz, Fabrizio Di Benedetto, Massimo Dominici
{"title":"将吉西他滨和输送可溶性 TRAIL 的间充质干细胞结合起来，靶向胰腺癌及其基质。","authors":"Giulia Grisendi, Massimiliano Dall'Ora, Giulia Casari, Giliola Spattini, Moein Farshchian, Aurora Melandri, Valentina Masicale, Fabio Lepore, Federico Banchelli, Riccardo Cuoghi Costantini, Angela D'Esposito, Chiara Chiavelli, Carlotta Spano, Andrea Spallanzani, Tiziana Petrachi, Elena Veronesi, Manuela Ferracin, Roberta Roncarati, Jonathan Vinet, Paolo Magistri, Barbara Catellani, Olivia Candini, Caterina Marra, Albino Eccher, Luca Reggiani Bonetti, Edwin M Horwtiz, Fabrizio Di Benedetto, Massimo Dominici","doi":"10.1016/j.xcrm.2024.101685","DOIUrl":null,"url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDAC) still has a poor response to therapies, partly due to their cancer-associated fibroblasts (CAFs). Here, we investigate the synergistic impact of a combinatory approach between a known chemotherapy agent, such as gemcitabine (GEM), and gene-modified human mesenchymal stromal/stem cells (MSCs) secreting the pro-apoptotic soluble (s)TRAIL (sTRAIL MSCs) on both PDAC cells and CAFs. The combo significantly impacts on PDAC survival in 2D and 3D models. In orthotopic xenograft models, GEM and sTRAIL MSCs induce tumor architecture shredding with a reduction of CK7- and CK8/18-positive cancer cells and the abrogation of spleen metastases. A cytotoxic effect on primary human CAFs is also observed along with an alteration of their transcriptome and a reduction of the related desmoplasia. Collectively, we demonstrate a promising therapeutic profile of combining GEM and sTRAIL MSCs to target both tumoral and stromal compartments in PDAC.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":null,"pages":null},"PeriodicalIF":11.7000,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11384958/pdf/","citationCount":"0","resultStr":"{\"title\":\"Combining gemcitabine and MSC delivering soluble TRAIL to target pancreatic adenocarcinoma and its stroma.\",\"authors\":\"Giulia Grisendi, Massimiliano Dall'Ora, Giulia Casari, Giliola Spattini, Moein Farshchian, Aurora Melandri, Valentina Masicale, Fabio Lepore, Federico Banchelli, Riccardo Cuoghi Costantini, Angela D'Esposito, Chiara Chiavelli, Carlotta Spano, Andrea Spallanzani, Tiziana Petrachi, Elena Veronesi, Manuela Ferracin, Roberta Roncarati, Jonathan Vinet, Paolo Magistri, Barbara Catellani, Olivia Candini, Caterina Marra, Albino Eccher, Luca Reggiani Bonetti, Edwin M Horwtiz, Fabrizio Di Benedetto, Massimo Dominici\",\"doi\":\"10.1016/j.xcrm.2024.101685\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Pancreatic ductal adenocarcinoma (PDAC) still has a poor response to therapies, partly due to their cancer-associated fibroblasts (CAFs). Here, we investigate the synergistic impact of a combinatory approach between a known chemotherapy agent, such as gemcitabine (GEM), and gene-modified human mesenchymal stromal/stem cells (MSCs) secreting the pro-apoptotic soluble (s)TRAIL (sTRAIL MSCs) on both PDAC cells and CAFs. The combo significantly impacts on PDAC survival in 2D and 3D models. In orthotopic xenograft models, GEM and sTRAIL MSCs induce tumor architecture shredding with a reduction of CK7- and CK8/18-positive cancer cells and the abrogation of spleen metastases. A cytotoxic effect on primary human CAFs is also observed along with an alteration of their transcriptome and a reduction of the related desmoplasia. Collectively, we demonstrate a promising therapeutic profile of combining GEM and sTRAIL MSCs to target both tumoral and stromal compartments in PDAC.</p>\",\"PeriodicalId\":9822,\"journal\":{\"name\":\"Cell Reports Medicine\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":11.7000,\"publicationDate\":\"2024-08-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11384958/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cell Reports Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.xcrm.2024.101685\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell Reports Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.xcrm.2024.101685","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
Combining gemcitabine and MSC delivering soluble TRAIL to target pancreatic adenocarcinoma and its stroma.
Pancreatic ductal adenocarcinoma (PDAC) still has a poor response to therapies, partly due to their cancer-associated fibroblasts (CAFs). Here, we investigate the synergistic impact of a combinatory approach between a known chemotherapy agent, such as gemcitabine (GEM), and gene-modified human mesenchymal stromal/stem cells (MSCs) secreting the pro-apoptotic soluble (s)TRAIL (sTRAIL MSCs) on both PDAC cells and CAFs. The combo significantly impacts on PDAC survival in 2D and 3D models. In orthotopic xenograft models, GEM and sTRAIL MSCs induce tumor architecture shredding with a reduction of CK7- and CK8/18-positive cancer cells and the abrogation of spleen metastases. A cytotoxic effect on primary human CAFs is also observed along with an alteration of their transcriptome and a reduction of the related desmoplasia. Collectively, we demonstrate a promising therapeutic profile of combining GEM and sTRAIL MSCs to target both tumoral and stromal compartments in PDAC.
Cell Reports MedicineBiochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (all)
CiteScore
15.00
自引率
1.40%
发文量
231
审稿时长
40 days
期刊介绍：
Cell Reports Medicine is an esteemed open-access journal by Cell Press that publishes groundbreaking research in translational and clinical biomedical sciences, influencing human health and medicine.
Our journal ensures wide visibility and accessibility, reaching scientists and clinicians across various medical disciplines. We publish original research that spans from intriguing human biology concepts to all aspects of clinical work. We encourage submissions that introduce innovative ideas, forging new paths in clinical research and practice. We also welcome studies that provide vital information, enhancing our understanding of current standards of care in diagnosis, treatment, and prognosis. This encompasses translational studies, clinical trials (including long-term follow-ups), genomics, biomarker discovery, and technological advancements that contribute to diagnostics, treatment, and healthcare. Additionally, studies based on vertebrate model organisms are within the scope of the journal, as long as they directly relate to human health and disease.
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