Establishment of Pancreatic Cancer-Derived Tumor Organoids and Fibroblasts From Fresh Tissue

Díaz-Alejo, Jesús Frutos; April-Monn, Simon Leonhard; Cihova, Marina; Buociková, Verona; López, J. Villalón; Urbanova, Maria; Lechuga, Carmen G.; Tomáš, Miroslav; Dubovan, Peter; Sánchez, Beatríz; Páez, Sonia Camaño; Sanjuánbenito, Alfonso; Lobo, Eduardo; Heras, Elena de las; Guerra, Carmen; Pinta, Carolina de la; Barreto, Emma; Garrote, M. Rodriguez; Carrato, Alfredo; Ruiz-Cañas, Laura; Sáinz, Bruno; Torres, Ana Olivares; Smolkova, Bozena; Earl, Julie

doi:10.3791/65229

Cited by 2 publications

(1 citation statement)

References 12 publications

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“…Organoids are unique 3D culture models that can self-organize in contained structures. Pancreatic 3D organoids can be generated relatively quickly from small amounts of tissue, allowing drug and therapy testing [187]. Benefits of cancer organoids include the retention of cancer cell heterogeneity, histological features, and/or genetic and mutational status.…”

Section: Available Pdac Models For Testing the Efficacy Of Ndds: Pros...mentioning

confidence: 99%

Nanomedicine and epigenetics: New alliances to increase the odds in pancreatic cancer survival

Urbanova

Cihova

Buociková

et al. 2023

Biomedicine & Pharmacotherapy

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Section: Available Pdac Models For Testing the Efficacy Of Ndds: Pros...mentioning

confidence: 99%

Nanomedicine and epigenetics: New alliances to increase the odds in pancreatic cancer survival

Urbanova

Cihova

Buociková

et al. 2023

Biomedicine & Pharmacotherapy

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Reprogramming tumor-associated macrophages with lipid nanosystems reduces PDAC tumor burden and liver metastasis

Palencia-Campos,

Ruiz-Cañas,

Abal-Sanisidro

et al. 2024

J Nanobiotechnol

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Background Pancreatic ductal adenocarcinoma (PDAC) requires innovative therapeutic strategies to counteract its progression and metastatic potential. Since the majority of patients are diagnosed with advanced metastatic disease, treatment strategies targeting not only the primary tumor but also metastatic lesions are needed. Tumor-Associated Macrophages (TAMs) have emerged as central players, significantly influencing PDAC progression and metastasis. Our objective was to validate an innovative therapeutic strategy involving the reprogramming of TAMs using lipid nanosystems to prevent the formation of a pro-metastatic microenvironment in the liver. Results In vitro results demonstrate that M2-polarized macrophages lose their M2-phenotype following treatment with lipid nanoemulsions composed of vitamin E and sphingomyelin (VitE:SM), transitioning to an M0/M1 state. Specifically, VitE:SM nanoemulsion treatment decreased the expression of macrophage M2 markers such as Arg1 and Egr2, while M1 markers such as Cd86, Il-1b and Il-12b increased. Additionally, the TGF-βR1 inhibitor Galunisertib (LY2157299) was loaded into VitE:SM nanoemulsions and delivered to C57BL/6 mice orthotopically injected with KPC PDAC tumor cells. Treated mice showed diminished primary tumor growth and reduced TAM infiltration in the liver. Moreover, we observed a decrease in liver metastasis with the nanoemulsion treatment in an intrasplenic model of PDAC liver metastasis. Finally, we validated the translatability of our VitE:SM nanosystem therapy in a human cell-based 3D co-culture model in vivo, underscoring the pivotal role of macrophages in the nanosystem’s therapeutic effect in the context of human PDAC metastasis. Conclusions The demonstrated effectiveness and safety of our nanosystem therapy highlights a promising therapeutic approach for PDAC, showcasing its potential in reprogramming TAMs and mitigating the occurrence of liver metastasis. Graphical abstract

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Establishment of Pancreatic Cancer-Derived Tumor Organoids and Fibroblasts From Fresh Tissue

Abstract: Cancer (CIBERONC) 3 Biobank and Biomodels Platform (PT20/0045), ISCIII research and development platforms in biomedicine and health

Cited by 2 publications

References 12 publications

Nanomedicine and epigenetics: New alliances to increase the odds in pancreatic cancer survival

Nanomedicine and epigenetics: New alliances to increase the odds in pancreatic cancer survival

Reprogramming tumor-associated macrophages with lipid nanosystems reduces PDAC tumor burden and liver metastasis

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