Recellularized Colorectal Cancer Patient-Derived Scaffolds as In Vitro Pre-Clinical 3D Model for Drug Screening

Colorectal cancer (CRC) shows highly ineffective therapeutic management. An urgent unmet need is the random assignment to adjuvant chemotherapy of high-risk stage II and stage III CRC patients without any predictive factor of efficacy. In the field of drug discovery, a critical step is the preclinical evaluation of drug cytotoxicity, efficacy, and efficiency. We proposed a patient-derived 3D preclinical model for drug evaluation that could mimic in vitro the patient’s disease. Surgically resected CRC tissue and adjacent healthy colon mucosa were decellularized by a detergent-enzymatic treatment. Scaffolds were recellularized with HT29 and HCT116 cells. Qualitative and quantitative characterization of matched recellularized samples were evaluated through histology, immunofluorescences, scanning electron microscopy, and DNA amount quantification. A chemosensitivity test was performed using an increasing concentration of 5-fluorouracil (5FU). In vivo studies were carried out using zebrafish (<i<Danio rerio</i<) animal model. Permeability test and drug absorption were also determined. The decellularization protocol allowed the preservation of the original structure and ultrastructure. Five days after recellularization with HT29 and HCT116 cell lines, the 3D CRC model exhibited reduced sensitivity to 5FU treatments compared with conventional 2D cultures. Calculated the half maximal inhibitory concentration (IC<sub<50</sub<) for HT29 treated with 5FU resulted in 11.5 µM in 3D and 1.3 µM in 2D, and for HCT116, 9.87 µM in 3D and 1.7 µM in 2D. In xenograft experiments, HT29 extravasation was detected after 4 days post-injection, and we obtained a 5FU IC<sub<50</sub< fully comparable to that observed in the 3D CRC model. Using confocal microscopy, we demonstrated that the drug diffused through the repopulated 3D CRC scaffolds and co-localized with the cell nuclei. The bioengineered CRC 3D model could be a reliable preclinical patient-specific platform to bridge the gap between in vitro and in vivo drug testing assays and provide effective cancer treatment. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Francesca Sensi [verfasserIn] Edoardo D’Angelo [verfasserIn] Martina Piccoli [verfasserIn] Piero Pavan [verfasserIn] Francesca Mastrotto [verfasserIn] Paolo Caliceti [verfasserIn] Andrea Biccari [verfasserIn] Diana Corallo [verfasserIn] Luca Urbani [verfasserIn] Matteo Fassan [verfasserIn] Gaya Spolverato [verfasserIn] Pietro Riello [verfasserIn] Salvatore Pucciarelli [verfasserIn] Marco Agostini [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2020

Schlagwörter:	3d culture model colorectal cancer extracellular matrix decellularization drug test response to treatment

Übergeordnetes Werk:	In: Cancers - MDPI AG, 2010, 12(2020), 3, p 681
Übergeordnetes Werk:	volume:12 ; year:2020 ; number:3, p 681

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3390/cancers12030681

Katalog-ID:	DOAJ006550428

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allfields	10.3390/cancers12030681 doi (DE-627)DOAJ006550428 (DE-599)DOAJ4e91961a61bb4870a69965021482c82a DE-627 ger DE-627 rakwb eng RC254-282 Francesca Sensi verfasserin aut Recellularized Colorectal Cancer Patient-Derived Scaffolds as In Vitro Pre-Clinical 3D Model for Drug Screening 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Colorectal cancer (CRC) shows highly ineffective therapeutic management. An urgent unmet need is the random assignment to adjuvant chemotherapy of high-risk stage II and stage III CRC patients without any predictive factor of efficacy. In the field of drug discovery, a critical step is the preclinical evaluation of drug cytotoxicity, efficacy, and efficiency. We proposed a patient-derived 3D preclinical model for drug evaluation that could mimic in vitro the patient’s disease. Surgically resected CRC tissue and adjacent healthy colon mucosa were decellularized by a detergent-enzymatic treatment. Scaffolds were recellularized with HT29 and HCT116 cells. Qualitative and quantitative characterization of matched recellularized samples were evaluated through histology, immunofluorescences, scanning electron microscopy, and DNA amount quantification. A chemosensitivity test was performed using an increasing concentration of 5-fluorouracil (5FU). In vivo studies were carried out using zebrafish (<i<Danio rerio</i<) animal model. Permeability test and drug absorption were also determined. The decellularization protocol allowed the preservation of the original structure and ultrastructure. Five days after recellularization with HT29 and HCT116 cell lines, the 3D CRC model exhibited reduced sensitivity to 5FU treatments compared with conventional 2D cultures. Calculated the half maximal inhibitory concentration (IC<sub<50</sub<) for HT29 treated with 5FU resulted in 11.5 µM in 3D and 1.3 µM in 2D, and for HCT116, 9.87 µM in 3D and 1.7 µM in 2D. In xenograft experiments, HT29 extravasation was detected after 4 days post-injection, and we obtained a 5FU IC<sub<50</sub< fully comparable to that observed in the 3D CRC model. Using confocal microscopy, we demonstrated that the drug diffused through the repopulated 3D CRC scaffolds and co-localized with the cell nuclei. The bioengineered CRC 3D model could be a reliable preclinical patient-specific platform to bridge the gap between in vitro and in vivo drug testing assays and provide effective cancer treatment. 3d culture model colorectal cancer extracellular matrix decellularization drug test response to treatment Neoplasms. Tumors. Oncology. Including cancer and carcinogens Edoardo D’Angelo verfasserin aut Martina Piccoli verfasserin aut Piero Pavan verfasserin aut Francesca Mastrotto verfasserin aut Paolo Caliceti verfasserin aut Andrea Biccari verfasserin aut Diana Corallo verfasserin aut Luca Urbani verfasserin aut Matteo Fassan verfasserin aut Gaya Spolverato verfasserin aut Pietro Riello verfasserin aut Salvatore Pucciarelli verfasserin aut Marco Agostini verfasserin aut In Cancers MDPI AG, 2010 12(2020), 3, p 681 (DE-627)614095670 (DE-600)2527080-1 20726694 nnns volume:12 year:2020 number:3, p 681 https://doi.org/10.3390/cancers12030681 kostenfrei https://doaj.org/article/4e91961a61bb4870a69965021482c82a kostenfrei https://www.mdpi.com/2072-6694/12/3/681 kostenfrei https://doaj.org/toc/2072-6694 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2020 3, p 681
spelling	10.3390/cancers12030681 doi (DE-627)DOAJ006550428 (DE-599)DOAJ4e91961a61bb4870a69965021482c82a DE-627 ger DE-627 rakwb eng RC254-282 Francesca Sensi verfasserin aut Recellularized Colorectal Cancer Patient-Derived Scaffolds as In Vitro Pre-Clinical 3D Model for Drug Screening 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Colorectal cancer (CRC) shows highly ineffective therapeutic management. An urgent unmet need is the random assignment to adjuvant chemotherapy of high-risk stage II and stage III CRC patients without any predictive factor of efficacy. In the field of drug discovery, a critical step is the preclinical evaluation of drug cytotoxicity, efficacy, and efficiency. We proposed a patient-derived 3D preclinical model for drug evaluation that could mimic in vitro the patient’s disease. Surgically resected CRC tissue and adjacent healthy colon mucosa were decellularized by a detergent-enzymatic treatment. Scaffolds were recellularized with HT29 and HCT116 cells. Qualitative and quantitative characterization of matched recellularized samples were evaluated through histology, immunofluorescences, scanning electron microscopy, and DNA amount quantification. A chemosensitivity test was performed using an increasing concentration of 5-fluorouracil (5FU). In vivo studies were carried out using zebrafish (<i<Danio rerio</i<) animal model. Permeability test and drug absorption were also determined. The decellularization protocol allowed the preservation of the original structure and ultrastructure. Five days after recellularization with HT29 and HCT116 cell lines, the 3D CRC model exhibited reduced sensitivity to 5FU treatments compared with conventional 2D cultures. Calculated the half maximal inhibitory concentration (IC<sub<50</sub<) for HT29 treated with 5FU resulted in 11.5 µM in 3D and 1.3 µM in 2D, and for HCT116, 9.87 µM in 3D and 1.7 µM in 2D. In xenograft experiments, HT29 extravasation was detected after 4 days post-injection, and we obtained a 5FU IC<sub<50</sub< fully comparable to that observed in the 3D CRC model. Using confocal microscopy, we demonstrated that the drug diffused through the repopulated 3D CRC scaffolds and co-localized with the cell nuclei. The bioengineered CRC 3D model could be a reliable preclinical patient-specific platform to bridge the gap between in vitro and in vivo drug testing assays and provide effective cancer treatment. 3d culture model colorectal cancer extracellular matrix decellularization drug test response to treatment Neoplasms. Tumors. Oncology. Including cancer and carcinogens Edoardo D’Angelo verfasserin aut Martina Piccoli verfasserin aut Piero Pavan verfasserin aut Francesca Mastrotto verfasserin aut Paolo Caliceti verfasserin aut Andrea Biccari verfasserin aut Diana Corallo verfasserin aut Luca Urbani verfasserin aut Matteo Fassan verfasserin aut Gaya Spolverato verfasserin aut Pietro Riello verfasserin aut Salvatore Pucciarelli verfasserin aut Marco Agostini verfasserin aut In Cancers MDPI AG, 2010 12(2020), 3, p 681 (DE-627)614095670 (DE-600)2527080-1 20726694 nnns volume:12 year:2020 number:3, p 681 https://doi.org/10.3390/cancers12030681 kostenfrei https://doaj.org/article/4e91961a61bb4870a69965021482c82a kostenfrei https://www.mdpi.com/2072-6694/12/3/681 kostenfrei https://doaj.org/toc/2072-6694 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2020 3, p 681
allfields_unstemmed	10.3390/cancers12030681 doi (DE-627)DOAJ006550428 (DE-599)DOAJ4e91961a61bb4870a69965021482c82a DE-627 ger DE-627 rakwb eng RC254-282 Francesca Sensi verfasserin aut Recellularized Colorectal Cancer Patient-Derived Scaffolds as In Vitro Pre-Clinical 3D Model for Drug Screening 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Colorectal cancer (CRC) shows highly ineffective therapeutic management. An urgent unmet need is the random assignment to adjuvant chemotherapy of high-risk stage II and stage III CRC patients without any predictive factor of efficacy. In the field of drug discovery, a critical step is the preclinical evaluation of drug cytotoxicity, efficacy, and efficiency. We proposed a patient-derived 3D preclinical model for drug evaluation that could mimic in vitro the patient’s disease. Surgically resected CRC tissue and adjacent healthy colon mucosa were decellularized by a detergent-enzymatic treatment. Scaffolds were recellularized with HT29 and HCT116 cells. Qualitative and quantitative characterization of matched recellularized samples were evaluated through histology, immunofluorescences, scanning electron microscopy, and DNA amount quantification. A chemosensitivity test was performed using an increasing concentration of 5-fluorouracil (5FU). In vivo studies were carried out using zebrafish (<i<Danio rerio</i<) animal model. Permeability test and drug absorption were also determined. The decellularization protocol allowed the preservation of the original structure and ultrastructure. Five days after recellularization with HT29 and HCT116 cell lines, the 3D CRC model exhibited reduced sensitivity to 5FU treatments compared with conventional 2D cultures. Calculated the half maximal inhibitory concentration (IC<sub<50</sub<) for HT29 treated with 5FU resulted in 11.5 µM in 3D and 1.3 µM in 2D, and for HCT116, 9.87 µM in 3D and 1.7 µM in 2D. In xenograft experiments, HT29 extravasation was detected after 4 days post-injection, and we obtained a 5FU IC<sub<50</sub< fully comparable to that observed in the 3D CRC model. Using confocal microscopy, we demonstrated that the drug diffused through the repopulated 3D CRC scaffolds and co-localized with the cell nuclei. The bioengineered CRC 3D model could be a reliable preclinical patient-specific platform to bridge the gap between in vitro and in vivo drug testing assays and provide effective cancer treatment. 3d culture model colorectal cancer extracellular matrix decellularization drug test response to treatment Neoplasms. Tumors. Oncology. Including cancer and carcinogens Edoardo D’Angelo verfasserin aut Martina Piccoli verfasserin aut Piero Pavan verfasserin aut Francesca Mastrotto verfasserin aut Paolo Caliceti verfasserin aut Andrea Biccari verfasserin aut Diana Corallo verfasserin aut Luca Urbani verfasserin aut Matteo Fassan verfasserin aut Gaya Spolverato verfasserin aut Pietro Riello verfasserin aut Salvatore Pucciarelli verfasserin aut Marco Agostini verfasserin aut In Cancers MDPI AG, 2010 12(2020), 3, p 681 (DE-627)614095670 (DE-600)2527080-1 20726694 nnns volume:12 year:2020 number:3, p 681 https://doi.org/10.3390/cancers12030681 kostenfrei https://doaj.org/article/4e91961a61bb4870a69965021482c82a kostenfrei https://www.mdpi.com/2072-6694/12/3/681 kostenfrei https://doaj.org/toc/2072-6694 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2020 3, p 681
allfieldsGer	10.3390/cancers12030681 doi (DE-627)DOAJ006550428 (DE-599)DOAJ4e91961a61bb4870a69965021482c82a DE-627 ger DE-627 rakwb eng RC254-282 Francesca Sensi verfasserin aut Recellularized Colorectal Cancer Patient-Derived Scaffolds as In Vitro Pre-Clinical 3D Model for Drug Screening 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Colorectal cancer (CRC) shows highly ineffective therapeutic management. An urgent unmet need is the random assignment to adjuvant chemotherapy of high-risk stage II and stage III CRC patients without any predictive factor of efficacy. In the field of drug discovery, a critical step is the preclinical evaluation of drug cytotoxicity, efficacy, and efficiency. We proposed a patient-derived 3D preclinical model for drug evaluation that could mimic in vitro the patient’s disease. Surgically resected CRC tissue and adjacent healthy colon mucosa were decellularized by a detergent-enzymatic treatment. Scaffolds were recellularized with HT29 and HCT116 cells. Qualitative and quantitative characterization of matched recellularized samples were evaluated through histology, immunofluorescences, scanning electron microscopy, and DNA amount quantification. A chemosensitivity test was performed using an increasing concentration of 5-fluorouracil (5FU). In vivo studies were carried out using zebrafish (<i<Danio rerio</i<) animal model. Permeability test and drug absorption were also determined. The decellularization protocol allowed the preservation of the original structure and ultrastructure. Five days after recellularization with HT29 and HCT116 cell lines, the 3D CRC model exhibited reduced sensitivity to 5FU treatments compared with conventional 2D cultures. Calculated the half maximal inhibitory concentration (IC<sub<50</sub<) for HT29 treated with 5FU resulted in 11.5 µM in 3D and 1.3 µM in 2D, and for HCT116, 9.87 µM in 3D and 1.7 µM in 2D. In xenograft experiments, HT29 extravasation was detected after 4 days post-injection, and we obtained a 5FU IC<sub<50</sub< fully comparable to that observed in the 3D CRC model. Using confocal microscopy, we demonstrated that the drug diffused through the repopulated 3D CRC scaffolds and co-localized with the cell nuclei. The bioengineered CRC 3D model could be a reliable preclinical patient-specific platform to bridge the gap between in vitro and in vivo drug testing assays and provide effective cancer treatment. 3d culture model colorectal cancer extracellular matrix decellularization drug test response to treatment Neoplasms. Tumors. Oncology. Including cancer and carcinogens Edoardo D’Angelo verfasserin aut Martina Piccoli verfasserin aut Piero Pavan verfasserin aut Francesca Mastrotto verfasserin aut Paolo Caliceti verfasserin aut Andrea Biccari verfasserin aut Diana Corallo verfasserin aut Luca Urbani verfasserin aut Matteo Fassan verfasserin aut Gaya Spolverato verfasserin aut Pietro Riello verfasserin aut Salvatore Pucciarelli verfasserin aut Marco Agostini verfasserin aut In Cancers MDPI AG, 2010 12(2020), 3, p 681 (DE-627)614095670 (DE-600)2527080-1 20726694 nnns volume:12 year:2020 number:3, p 681 https://doi.org/10.3390/cancers12030681 kostenfrei https://doaj.org/article/4e91961a61bb4870a69965021482c82a kostenfrei https://www.mdpi.com/2072-6694/12/3/681 kostenfrei https://doaj.org/toc/2072-6694 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2020 3, p 681
allfieldsSound	10.3390/cancers12030681 doi (DE-627)DOAJ006550428 (DE-599)DOAJ4e91961a61bb4870a69965021482c82a DE-627 ger DE-627 rakwb eng RC254-282 Francesca Sensi verfasserin aut Recellularized Colorectal Cancer Patient-Derived Scaffolds as In Vitro Pre-Clinical 3D Model for Drug Screening 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Colorectal cancer (CRC) shows highly ineffective therapeutic management. An urgent unmet need is the random assignment to adjuvant chemotherapy of high-risk stage II and stage III CRC patients without any predictive factor of efficacy. In the field of drug discovery, a critical step is the preclinical evaluation of drug cytotoxicity, efficacy, and efficiency. We proposed a patient-derived 3D preclinical model for drug evaluation that could mimic in vitro the patient’s disease. Surgically resected CRC tissue and adjacent healthy colon mucosa were decellularized by a detergent-enzymatic treatment. Scaffolds were recellularized with HT29 and HCT116 cells. Qualitative and quantitative characterization of matched recellularized samples were evaluated through histology, immunofluorescences, scanning electron microscopy, and DNA amount quantification. A chemosensitivity test was performed using an increasing concentration of 5-fluorouracil (5FU). In vivo studies were carried out using zebrafish (<i<Danio rerio</i<) animal model. Permeability test and drug absorption were also determined. The decellularization protocol allowed the preservation of the original structure and ultrastructure. Five days after recellularization with HT29 and HCT116 cell lines, the 3D CRC model exhibited reduced sensitivity to 5FU treatments compared with conventional 2D cultures. Calculated the half maximal inhibitory concentration (IC<sub<50</sub<) for HT29 treated with 5FU resulted in 11.5 µM in 3D and 1.3 µM in 2D, and for HCT116, 9.87 µM in 3D and 1.7 µM in 2D. In xenograft experiments, HT29 extravasation was detected after 4 days post-injection, and we obtained a 5FU IC<sub<50</sub< fully comparable to that observed in the 3D CRC model. Using confocal microscopy, we demonstrated that the drug diffused through the repopulated 3D CRC scaffolds and co-localized with the cell nuclei. The bioengineered CRC 3D model could be a reliable preclinical patient-specific platform to bridge the gap between in vitro and in vivo drug testing assays and provide effective cancer treatment. 3d culture model colorectal cancer extracellular matrix decellularization drug test response to treatment Neoplasms. Tumors. Oncology. Including cancer and carcinogens Edoardo D’Angelo verfasserin aut Martina Piccoli verfasserin aut Piero Pavan verfasserin aut Francesca Mastrotto verfasserin aut Paolo Caliceti verfasserin aut Andrea Biccari verfasserin aut Diana Corallo verfasserin aut Luca Urbani verfasserin aut Matteo Fassan verfasserin aut Gaya Spolverato verfasserin aut Pietro Riello verfasserin aut Salvatore Pucciarelli verfasserin aut Marco Agostini verfasserin aut In Cancers MDPI AG, 2010 12(2020), 3, p 681 (DE-627)614095670 (DE-600)2527080-1 20726694 nnns volume:12 year:2020 number:3, p 681 https://doi.org/10.3390/cancers12030681 kostenfrei https://doaj.org/article/4e91961a61bb4870a69965021482c82a kostenfrei https://www.mdpi.com/2072-6694/12/3/681 kostenfrei https://doaj.org/toc/2072-6694 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2020 3, p 681
language	English
source	In Cancers 12(2020), 3, p 681 volume:12 year:2020 number:3, p 681
sourceStr	In Cancers 12(2020), 3, p 681 volume:12 year:2020 number:3, p 681
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	3d culture model colorectal cancer extracellular matrix decellularization drug test response to treatment Neoplasms. Tumors. Oncology. Including cancer and carcinogens
isfreeaccess_bool	true
container_title	Cancers
authorswithroles_txt_mv	Francesca Sensi @@aut@@ Edoardo D’Angelo @@aut@@ Martina Piccoli @@aut@@ Piero Pavan @@aut@@ Francesca Mastrotto @@aut@@ Paolo Caliceti @@aut@@ Andrea Biccari @@aut@@ Diana Corallo @@aut@@ Luca Urbani @@aut@@ Matteo Fassan @@aut@@ Gaya Spolverato @@aut@@ Pietro Riello @@aut@@ Salvatore Pucciarelli @@aut@@ Marco Agostini @@aut@@
publishDateDaySort_date	2020-01-01T00:00:00Z
hierarchy_top_id	614095670
id	DOAJ006550428
language_de	englisch
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callnumber-first	R - Medicine
author	Francesca Sensi
spellingShingle	Francesca Sensi misc RC254-282 misc 3d culture model misc colorectal cancer misc extracellular matrix misc decellularization misc drug test misc response to treatment misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens Recellularized Colorectal Cancer Patient-Derived Scaffolds as In Vitro Pre-Clinical 3D Model for Drug Screening
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topic_title	RC254-282 Recellularized Colorectal Cancer Patient-Derived Scaffolds as In Vitro Pre-Clinical 3D Model for Drug Screening 3d culture model colorectal cancer extracellular matrix decellularization drug test response to treatment
topic	misc RC254-282 misc 3d culture model misc colorectal cancer misc extracellular matrix misc decellularization misc drug test misc response to treatment misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
topic_unstemmed	misc RC254-282 misc 3d culture model misc colorectal cancer misc extracellular matrix misc decellularization misc drug test misc response to treatment misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
topic_browse	misc RC254-282 misc 3d culture model misc colorectal cancer misc extracellular matrix misc decellularization misc drug test misc response to treatment misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
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title	Recellularized Colorectal Cancer Patient-Derived Scaffolds as In Vitro Pre-Clinical 3D Model for Drug Screening
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title_full	Recellularized Colorectal Cancer Patient-Derived Scaffolds as In Vitro Pre-Clinical 3D Model for Drug Screening
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author_browse	Francesca Sensi Edoardo D’Angelo Martina Piccoli Piero Pavan Francesca Mastrotto Paolo Caliceti Andrea Biccari Diana Corallo Luca Urbani Matteo Fassan Gaya Spolverato Pietro Riello Salvatore Pucciarelli Marco Agostini
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author-letter	Francesca Sensi
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title_sort	recellularized colorectal cancer patient-derived scaffolds as in vitro pre-clinical 3d model for drug screening
callnumber	RC254-282
title_auth	Recellularized Colorectal Cancer Patient-Derived Scaffolds as In Vitro Pre-Clinical 3D Model for Drug Screening
abstract	Colorectal cancer (CRC) shows highly ineffective therapeutic management. An urgent unmet need is the random assignment to adjuvant chemotherapy of high-risk stage II and stage III CRC patients without any predictive factor of efficacy. In the field of drug discovery, a critical step is the preclinical evaluation of drug cytotoxicity, efficacy, and efficiency. We proposed a patient-derived 3D preclinical model for drug evaluation that could mimic in vitro the patient’s disease. Surgically resected CRC tissue and adjacent healthy colon mucosa were decellularized by a detergent-enzymatic treatment. Scaffolds were recellularized with HT29 and HCT116 cells. Qualitative and quantitative characterization of matched recellularized samples were evaluated through histology, immunofluorescences, scanning electron microscopy, and DNA amount quantification. A chemosensitivity test was performed using an increasing concentration of 5-fluorouracil (5FU). In vivo studies were carried out using zebrafish (<i<Danio rerio</i<) animal model. Permeability test and drug absorption were also determined. The decellularization protocol allowed the preservation of the original structure and ultrastructure. Five days after recellularization with HT29 and HCT116 cell lines, the 3D CRC model exhibited reduced sensitivity to 5FU treatments compared with conventional 2D cultures. Calculated the half maximal inhibitory concentration (IC<sub<50</sub<) for HT29 treated with 5FU resulted in 11.5 µM in 3D and 1.3 µM in 2D, and for HCT116, 9.87 µM in 3D and 1.7 µM in 2D. In xenograft experiments, HT29 extravasation was detected after 4 days post-injection, and we obtained a 5FU IC<sub<50</sub< fully comparable to that observed in the 3D CRC model. Using confocal microscopy, we demonstrated that the drug diffused through the repopulated 3D CRC scaffolds and co-localized with the cell nuclei. The bioengineered CRC 3D model could be a reliable preclinical patient-specific platform to bridge the gap between in vitro and in vivo drug testing assays and provide effective cancer treatment.
abstractGer	Colorectal cancer (CRC) shows highly ineffective therapeutic management. An urgent unmet need is the random assignment to adjuvant chemotherapy of high-risk stage II and stage III CRC patients without any predictive factor of efficacy. In the field of drug discovery, a critical step is the preclinical evaluation of drug cytotoxicity, efficacy, and efficiency. We proposed a patient-derived 3D preclinical model for drug evaluation that could mimic in vitro the patient’s disease. Surgically resected CRC tissue and adjacent healthy colon mucosa were decellularized by a detergent-enzymatic treatment. Scaffolds were recellularized with HT29 and HCT116 cells. Qualitative and quantitative characterization of matched recellularized samples were evaluated through histology, immunofluorescences, scanning electron microscopy, and DNA amount quantification. A chemosensitivity test was performed using an increasing concentration of 5-fluorouracil (5FU). In vivo studies were carried out using zebrafish (<i<Danio rerio</i<) animal model. Permeability test and drug absorption were also determined. The decellularization protocol allowed the preservation of the original structure and ultrastructure. Five days after recellularization with HT29 and HCT116 cell lines, the 3D CRC model exhibited reduced sensitivity to 5FU treatments compared with conventional 2D cultures. Calculated the half maximal inhibitory concentration (IC<sub<50</sub<) for HT29 treated with 5FU resulted in 11.5 µM in 3D and 1.3 µM in 2D, and for HCT116, 9.87 µM in 3D and 1.7 µM in 2D. In xenograft experiments, HT29 extravasation was detected after 4 days post-injection, and we obtained a 5FU IC<sub<50</sub< fully comparable to that observed in the 3D CRC model. Using confocal microscopy, we demonstrated that the drug diffused through the repopulated 3D CRC scaffolds and co-localized with the cell nuclei. The bioengineered CRC 3D model could be a reliable preclinical patient-specific platform to bridge the gap between in vitro and in vivo drug testing assays and provide effective cancer treatment.
abstract_unstemmed	Colorectal cancer (CRC) shows highly ineffective therapeutic management. An urgent unmet need is the random assignment to adjuvant chemotherapy of high-risk stage II and stage III CRC patients without any predictive factor of efficacy. In the field of drug discovery, a critical step is the preclinical evaluation of drug cytotoxicity, efficacy, and efficiency. We proposed a patient-derived 3D preclinical model for drug evaluation that could mimic in vitro the patient’s disease. Surgically resected CRC tissue and adjacent healthy colon mucosa were decellularized by a detergent-enzymatic treatment. Scaffolds were recellularized with HT29 and HCT116 cells. Qualitative and quantitative characterization of matched recellularized samples were evaluated through histology, immunofluorescences, scanning electron microscopy, and DNA amount quantification. A chemosensitivity test was performed using an increasing concentration of 5-fluorouracil (5FU). In vivo studies were carried out using zebrafish (<i<Danio rerio</i<) animal model. Permeability test and drug absorption were also determined. The decellularization protocol allowed the preservation of the original structure and ultrastructure. Five days after recellularization with HT29 and HCT116 cell lines, the 3D CRC model exhibited reduced sensitivity to 5FU treatments compared with conventional 2D cultures. Calculated the half maximal inhibitory concentration (IC<sub<50</sub<) for HT29 treated with 5FU resulted in 11.5 µM in 3D and 1.3 µM in 2D, and for HCT116, 9.87 µM in 3D and 1.7 µM in 2D. In xenograft experiments, HT29 extravasation was detected after 4 days post-injection, and we obtained a 5FU IC<sub<50</sub< fully comparable to that observed in the 3D CRC model. Using confocal microscopy, we demonstrated that the drug diffused through the repopulated 3D CRC scaffolds and co-localized with the cell nuclei. The bioengineered CRC 3D model could be a reliable preclinical patient-specific platform to bridge the gap between in vitro and in vivo drug testing assays and provide effective cancer treatment.
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