Organotypic primary blood vessel models of clear cell renal cell carcinoma for single-patient clinical trials

Virumbrales-Muñoz, María; Chen, Jiong; Ayuso, Jesús Manso; Lee, Moon-Hee; Abel, E. Jason; Beebe, David J.

doi:10.1039/d0lc00252f

Cited by 24 publications

(28 citation statements)

References 50 publications

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“…For CIS, a similar behavior was noted for low concentrations, whereas in higher concentrations, the value of GGT on the cells decreased and, on the outflow, increased significantly. Virumbrales-Muñoz et al [ 58 ] used a microfluidic device to recreate the blood vessel formation that occurs with the tumor growth. The authors used three patient-derived cancer cells on the model.…”

Section: Resultsmentioning

confidence: 99%

Organ-on-a-Chip Platforms for Drug Screening and Delivery in Tumor Cells: A Systematic Review

Gonçalves

Carvalho

Rodrigues

et al. 2022

Cancers

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The development of cancer models that rectify the simplicity of monolayer or static cell cultures physiologic microenvironment and, at the same time, replicate the human system more accurately than animal models has been a challenge in biomedical research. Organ-on-a-chip (OoC) devices are a solution that has been explored over the last decade. The combination of microfluidics and cell culture allows the design of a dynamic microenvironment suitable for the evaluation of treatments’ efficacy and effects, closer to the response observed in patients. This systematic review sums the studies from the last decade, where OoC with cancer cell cultures were used for drug screening assays. The studies were selected from three databases and analyzed following the research guidelines for systematic reviews proposed by PRISMA. In the selected studies, several types of cancer cells were evaluated, and the majority of treatments tested were standard chemotherapeutic drugs. Some studies reported higher drug resistance of the cultures on the OoC devices than on 2D cultures, which indicates the better resemblance to in vivo conditions of the former. Several studies also included the replication of the microvasculature or the combination of different cell cultures. The presence of vasculature can influence positively or negatively the drug efficacy since it contributes to a greater diffusion of the drug and also oxygen and nutrients. Co-cultures with liver cells contributed to the evaluation of the systemic toxicity of some drugs metabolites. Nevertheless, few studies used patient cells for the drug screening assays.

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Section: Resultsmentioning

confidence: 99%

Organ-on-a-Chip Platforms for Drug Screening and Delivery in Tumor Cells: A Systematic Review

Gonçalves

Carvalho

Rodrigues

et al. 2022

Cancers

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“…Therefore, the number, structure and distribution of new blood vessels in benign and malignant renal masses are obviously different. Angiography showed that there were new blood vessels in more than 90% of renal cancer lesions, which were mostly densely clustered [ 11 ]. The microvascular structure of different parts of renal carcinoma was observed by transmission electron microscopy.…”

Section: Discussionmentioning

confidence: 99%

The comparative study of color doppler flow imaging, superb microvascular imaging, contrast-enhanced ultrasound micro flow imaging in blood flow analysis of solid renal mass

Mao

Zhao

et al. 2022

Cancer Imaging

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Purposes To evaluate the value of Color Doppler Flow Imaging (CDFI), Superb Microvascular Imaging (SMI) and Contrast-enhanced Ultrasound Microflow Imaging (MFI) in display the microvascular blood flow signals in renal solid lesions. Methods 142 patients with 144 renal masses were examined by CDFI, SMI and MFI simultaneously. We compared the difference of blood flow grading and vascular architecture based on CDFI, SMI and MFI. Results The blood flow signals detection rates of CDFI, SMI and MFI were 78.5% (113/144), 88.9% (128/144) and 93.8% (135/144), respectively. Concentrated on blood flow grading, The coincidence rates of CDFI and SMI were 64.58% (93/144) and 81.25% (117/144) referring to MFI, respectively. Blood flow grade 2–3 in CDFI is significantly lower than SMI(x2 = 5.557, P = 0.018) and MFI (x2 = 10.165, P = 0.001). Whereas there was no significant difference between SMI and MFI (x2 = 2.372, P = 0.499). Concentrated on vascular architecture, the coincidence rates of CDFI and SMI were 56.25% (81/144) and 75.69% (109/144) referring to MFI, respectively. Vascular architecture type IV and V in CDFI was significantly lower than SMI (x2 = 18.217, P < 0.001) and MFI (x2 = 29.518, P < 0.001). Whereas there was no significant difference between SMI and MFI (x2 = 3.048, P = 0.550). The sensitivity and specificity of CDFI, SMI and MFI in the diagnosis of renal mass were 61.29% and 90.20%, 79.57% and 88.24%, 88.17% and 84.31% respectively. The areas under the ROC curve of the three were 0.757, 0.839 and 0.862, respectively. There was a statistically significant difference between CDFI and MFI (Z = 3.687, P = 0.0002), while there was no statistically significant difference between SMI and MFI (Z = 1.167, P = 0.2431). Conclusion SMI and MFI are superior to CDFI in showing blood flow signals in renal solid masses, and it can perform blood flow and vascular architecture more accurately. Advances in knowledge SMI is similar to MFI in its ability to display fine vessels and diagnostic efficiency, and has application value in the diagnosis and differential diagnosis of renal solid masses.

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“…After a rolling ball background subtraction, we projected 10 Z-planes per Z-stack. Then, sprouts were counted, and each sprout was manually traced from the lumen using the segmented line tool from which the length was measured [28] .…”

Section: Methodsmentioning

confidence: 99%

“…Fortunately, microscale organotypic models bridge the gap between these conventional approaches as they offer the advantage of recapitulating in vivo 3D geometries and interactions, allowing more precise interrogation of microenvironmental conditions [ 25 , 26 ]. Patient-specific microscale organotypic models have emerged recently and have been leveraged to examine patient-specific gene expression alterations and responses to anti-angiogenic therapies [26] , [27] , [28] . Thus, we hypothesise that microscale organotypic models focused on elucidating the contribution of patient-specific TDF in lymphangiogenesis would help better understand and target head and neck cancer in a patient-specific manner.…”

Section: Introductionmentioning

confidence: 99%

Primary head and neck tumour-derived fibroblasts promote lymphangiogenesis in a lymphatic organotypic co-culture model

et al. 2021

Self Cite

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Background: In head and neck cancer, intratumour lymphatic density and tumour lymphangiogenesis have been correlated with lymphatic metastasis, making lymphangiogenesis a promising therapeutic target. However, inter-patient tumour heterogeneity makes it challenging to predict tumour progression and lymph node metastasis. Understanding the lymphangiogenic-promoting factors leading to metastasis (e.g., tumourderived fibroblasts or TDF), would help develop strategies to improve patient outcomes. Methods: A microfluidic in vitro model of a tubular lymphatic vessel was co-cultured with primary TDF from head and neck cancer patients to evaluate the effect of TDF on lymphangiogenesis. We assessed the length and number of lymphangiogenic sprouts and vessel permeability via microscopy and image analysis. Finally, we characterised lymphatic vessel conditioning by TDF via RT-qPCR. Findings: Lymphatic vessels were conditioned by the TDF in a patient-specific manner. Specifically, the presence of TDF induced sprouting, altered vessel permeability, and increased the expression of pro-lymphangiogenic genes. Gene expression and functional responses in the fibroblast-conditioned lymphatic vessels were consistent with the patient tumour stage and lymph node status. IGF-1, upregulated among patients, was targeted to validate our personalised medicine approach. Interestingly, IGF-1 blockade was not effective across different patients. Interpretation: The use of lymphatic organotypic models incorporating head and neck TDF provides insight into the pathways leading to lymphangiogenesis in each patient. This model provided a platform to test antiangiogenic therapeutics and inform of their effectiveness for individual patients.

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Organotypic primary blood vessel models of clear cell renal cell carcinoma for single-patient clinical trials

Abstract: Identification and testing of personalized anti-angiogenic treatments for clear cell renal cell carcinoma using patient-derived microfluidic models of normal and tumor-associated blood vessels.

Cited by 24 publications

References 50 publications

Organ-on-a-Chip Platforms for Drug Screening and Delivery in Tumor Cells: A Systematic Review

Organ-on-a-Chip Platforms for Drug Screening and Delivery in Tumor Cells: A Systematic Review

The comparative study of color doppler flow imaging, superb microvascular imaging, contrast-enhanced ultrasound micro flow imaging in blood flow analysis of solid renal mass

Primary head and neck tumour-derived fibroblasts promote lymphangiogenesis in a lymphatic organotypic co-culture model

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