Validation of a 3D perfused cell culture platform as a tool for humanised preclinical drug testing in breast cancer using established cell lines and patient-derived tissues

Liu, Peng; Roberts, Sophie; Shoemaker, James T.; Vukasinovic, Jelena; Tomlinson, Darren; Speirs, Valerie

doi:10.1371/journal.pone.0283044

Cited by 3 publications

(2 citation statements)

References 36 publications

(44 reference statements)

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“…Gelatine sponges and foam supports have been used with variable success for pancreatic ductal adenocarcinoma and prostate cancers 71,72 . Recent efforts are maximising throughput and enhancing physiological recapitulation using microfluidics and tumour‐on‐a‐chip technologies with refined extracellular matrices, constant perfusion of media and drugs, and even blood substitutes 51,73 …”

Section: Short‐term Ex Vivo Tumour Culturementioning

confidence: 99%

“…71,72 Recent efforts are maximising throughput and enhancing physiological recapitulation using microfluidics and tumour-ona-chip technologies with refined extracellular matrices, constant perfusion of media and drugs, and even blood substitutes. 51,73 Culture media ranges from standard basal media to carefully optimised combinations with tissue-specific supplements, such as B-27, insulin-transferrin-selenium, hydrocortisone and cholera toxin. 56,63 There is no consensus on serum supplementation; some studies suggest serum interferes with native behaviour and short-term culture TA B L E 2 Comparison of key features of in vitro and ex vivo tumour cultures.…”

Section: Short-term Culturementioning

confidence: 99%

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Ex vivo therapeutic screening of metastatic cSCC: A review of methodological considerations for clinical implementation

Conley,

Perry,

Ashford

et al. 2024

Experimental Dermatology

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Cutaneous squamous cell carcinoma (cSCC) is the second most common malignancy worldwide, with most deaths caused by locally advanced and metastatic disease. Treatment of resectable metastases is typically limited to invasive surgery with adjuvant radiotherapy; however, many patients fail to respond and there is minimal data to predict response or propose effective alternatives. Precision medicine could improve this, though genomic biomarkers remain elusive in the high mutational background and genomic complexity of cSCC. A phenotypic approach to precision medicine using patient‐derived ex vivo tumour models is gaining favour for its capacity to directly assess biological responses to therapeutics as a functional, predictive biomarker. However, the use of ex vivo models for guiding therapeutic selection has yet to be employed for metastatic cSCC. This review will therefore evaluate the existing experimental models of metastatic cSCC and discuss how ex vivo methods could overcome the shortcomings of these existing models. Disease‐specific considerations for a prospective methodological pipeline will also be discussed in the context of precision medicine.

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Section: Short‐term Ex Vivo Tumour Culturementioning

confidence: 99%

Section: Short-term Culturementioning

confidence: 99%

Ex vivo therapeutic screening of metastatic cSCC: A review of methodological considerations for clinical implementation

Conley,

Perry,

Ashford

et al. 2024

Experimental Dermatology

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Three-Dimensional Cell Culture Scaffold Supports Capillary-Like Network Formation by Endothelial Cells Derived from Porcine-Induced Pluripotent Stem Cells

Liao,

Chen,

Lin

et al. 2024

Cells Tissues Organs

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Introduction: Endothelial cells (EC) can be generated from porcine induced pluripotent stem cells (piPSC), but poor efficiency in driving EC differentiation hampers their application and efficacy. Additionally, the culture of piPSC-derived EC (piPSC-EC) on 3D scaffolds has not been fully reported yet. Here, we report a method to improve the generation of EC differentiation from piPSC and to facilitate their culture on 3D scaffolds, providing a potential resource for in vitro drug testing and the generation of tissue-engineered vascular grafts (TEVG). Methods: We initiated the differentiation of piPSC into EC by seeding them on laminin 411 and employing a three-stage protocol, which involved the use of distinct EC differentiation media supplemented with CHIR99021, BMP4, VEGF, and bFGF. Results: piPSC-EC not only expressed EC markers such as CD31, VE-cadherin, and vWF but also exhibited an upregulation of EC marker genes, including CD31, CD34, VEGFR2, VE-cadherin, and vWF. They exhibited functional characteristics similar to those of porcine coronary artery endothelial cells (PCAECs), such as tube formation and Dil-Ac-LDL uptake. Furthermore, when cultured on 3D scaffolds, piPSC-EC developed a 3D morphology and were capable of forming an endothelial layer and engineering capillary-like networks, though these lacked lumen structures. Conclusion: Our study not only advances the generation of EC from piPSC through an inhibitor and growth factor cocktail but also provides a promising approach for constructing vascular network-like structures. Importantly, these findings open new avenues for drug discovery in vitro and tissue engineering in vivo.

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The Transformative Role of 3D Culture Models in Triple-Negative Breast Cancer Research

Bittman-Soto,

Thomas,

Ganshert

et al. 2024

Cancers

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Advancements in cell culturing techniques have allowed the development of three-dimensional (3D) cell culture models sourced directly from patients’ tissues and tumors, faithfully replicating the native tissue environment. These models provide a more clinically relevant platform for studying disease progression and treatment responses compared to traditional two-dimensional (2D) models. Patient-derived organoids (PDOs) and patient-derived xenograft organoids (PDXOs) emerge as innovative 3D cancer models capable of accurately mimicking the tumor’s unique features, enhancing our understanding of tumor complexities, and predicting clinical outcomes. Triple-negative breast cancer (TNBC) poses significant clinical challenges due to its aggressive nature, propensity for early metastasis, and limited treatment options. TNBC PDOs and PDXOs have significantly contributed to the comprehension of TNBC, providing novel insights into its underlying mechanism and identifying potential therapeutic targets. This review explores the transformative role of various 3D cancer models in elucidating TNBC pathogenesis and guiding novel therapeutic strategies. It also provides an overview of diverse 3D cell culture models, derived from cell lines and tumors, highlighting their advantages and culturing challenges. Finally, it delves into live-cell imaging techniques, endpoint assays, and alternative cell culture media and methodologies, such as scaffold-free and scaffold-based systems, essential for advancing 3D cancer model research and development.

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Validation of a 3D perfused cell culture platform as a tool for humanised preclinical drug testing in breast cancer using established cell lines and patient-derived tissues

Cited by 3 publications

References 36 publications

Ex vivo therapeutic screening of metastatic cSCC: A review of methodological considerations for clinical implementation

Ex vivo therapeutic screening of metastatic cSCC: A review of methodological considerations for clinical implementation

Three-Dimensional Cell Culture Scaffold Supports Capillary-Like Network Formation by Endothelial Cells Derived from Porcine-Induced Pluripotent Stem Cells

The Transformative Role of 3D Culture Models in Triple-Negative Breast Cancer Research

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