A multilayered epithelial mucosa model of head neck squamous cell carcinoma for analysis of tumor-microenvironment interactions and drug development

Gronbach, Leonie; Wolff, Christopher; Klinghammer, Konrad; Stellmacher, Johannes; Jurmeister, Philipp; Alexiev, Ulrike; Schäfer‐Korting, Monika; Tinhofer, Ingeborg; Keilholz, Ulrich; Zoschke, Christian

doi:10.1016/j.biomaterials.2020.120277

Cited by 10 publications

(20 citation statements)

References 50 publications

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“…The tumor-cell line SCC-25 from the tongue (RRID: CVCL_1682, Rheinwald and Beckett, 1981) was a generous gift from Howard Green, Dana-Farber Cancer Institute (Boston, MA, United States). The detailed composition and origin of the construct growth and construct differentiation media were described elsewhere (Gronbach et al, 2020). Here, these media were supplemented with the transforming growth factor (TGF)-β1 and aprotinin, obtained from ThermoFisher Scientific (Waltham, MA, United States) and Merck.…”

Section: Methodsmentioning

confidence: 99%

“…All cultures were kept at 37 • C and 5% CO 2 in a humidified atmosphere. The building of collagen-based oral mucosa models was described previously (Gronbach et al, 2020). Briefly, 1 × 10 5 human oral fibroblasts per model were mixed with a buffered solution and added to collagen.…”

Section: Multilayered Oral Mucosa Model Buildingmentioning

confidence: 99%

“…Recently, we developed normal and tumor oral mucosa models emulating head and neck cancer, with a collagen scaffold (Gronbach et al, 2020) to improve non-clinical drug evaluation. The 3D model showed large similarities in morphology, grading, and protein expression profiles to patient's tumors.…”

Section: Introductionmentioning

confidence: 99%

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Primary Extracellular Matrix Enables Long-Term Cultivation of Human Tumor Oral Mucosa Models

Gronbach

Jurmeister

Schäfer‐Korting

et al. 2020

Front. Bioeng. Biotechnol.

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3D tumor models clearly outperform 2D cell cultures in recapitulating tissue architecture and drug response. However, their potential in understanding treatment efficacy and resistance development should be better exploited if also long-term effects of treatment could be assessed in vitro. The main disadvantages of the matrices commonly used for in vitro culture are their limited cultivation time and the low comparability with patient-specific matrix properties. Extended cultivation periods are feasible when primary human cells produce the extracellular matrix in situ. Herein, we adapted the hyalograft-3D approach from reconstructed human skin to normal and tumor oral mucosa models and compared the results to bovine collagen-based models. The hyalograft models showed similar morphology and cell proliferation after 7 weeks compared to collagen-based models after 2 weeks of cultivation. Tumor thickness and VEGF expression increased in hyalograft-based tumor models, whereas expression of laminin-332, tenascin C, and hypoxia-inducible factor 1α was lower than in collagen-based models. Taken together, the in situ produced extracellular matrix better confined tumor invasion in the first part of the cultivation period, with continuous tumor proliferation and increasing invasion later on. This proof-of-concept study showed the successful transfer of the hyalograft approach to tumor oral mucosa models and lays the foundation for the assessment of long-term drug treatment effects. Moreover, the use of an animal-derived extracellular matrix is avoided.

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Section: Methodsmentioning

confidence: 99%

Section: Multilayered Oral Mucosa Model Buildingmentioning

confidence: 99%

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Primary Extracellular Matrix Enables Long-Term Cultivation of Human Tumor Oral Mucosa Models

Gronbach

Jurmeister

Schäfer‐Korting

et al. 2020

Front. Bioeng. Biotechnol.

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“…However, donor-site morbidity for autografts and immunogenicity for xenografts and allografts can limit their application. 10 , 11 Consequently, additional treatment options for bone defects are urgently needed.…”

Section: Introductionmentioning

confidence: 99%

Ursolic Acid Loaded-Mesoporous Hydroxylapatite/ Chitosan Therapeutic Scaffolds Regulate Bone Regeneration Ability by Promoting the M2-Type Polarization of Macrophages

Yu¹,

Wang²,

Liu³

et al. 2021

IJN

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Purpose Mesoporous hydroxylapatite (MHAP) might be important for bone regeneration, and ursolic acid (UA) has anti-inflammatory effects. Accordingly, we developed, for the first time, ursolic acid-loaded MHAP-chitosan (MHAP-CS-UA) scaffolds to treat bone defects. Methods In vitro, we synthesize biomaterial scaffolds. By SEM, XRD, EDS and FTIR, we test the performance of the hybrid scaffolds. By drug release, flow cytometry, immunofluorescence, alizarin red staining, and Western blotting, we test the anti-inflammatory and osteo-inductive properties of scaffolds. In vivo, we verify osseointegration ability and bone regeneration. Results The MHAP is a rod-shaped structure with a length of 100~300nm and a diameter of 40~60nm. The critical structure gives the micro-scaffold a property of control release due to the pore sizes of 1.6~4.3 nm in hydroxyapatite and the hydrogen bonding between the scaffolds and UA drugs. The released UA drugs could notably inhibit the polarization of macrophages to pro-inflammatory macrophages (M1 type) and promote the expression of osteogenic-related genes (COL1, ALP and OPG) and osteogenic-related proteins (BMP-2, RUNX2 and COL1). Conclusion The MHAP-CS-UA scaffolds have good anti-inflammatory, osseointegration, osteo-inductivity and bone regeneration. And they will be the novel and promising candidates to cure the bone disease.

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“…The characterization of this RhoB containing DL is further accompanied by proof‐of‐principle experiments in skin tissue—a tissue that is highly relevant in topical drug application and the development of dermal and transdermal drug delivery systems [2, 13b, 17] . In the aged population, tissues including skin and mucous membranes of the oral cavity are prone to tumors, [9f, 18] but 96 % of anticancer drug candidates from preclinical studies fail in human [19] . DL labeling for insight into spatially resolved tissue concentrations quantified by EPR and FLIM offers an approach to method validation [1] .…”

Section: Introductionmentioning

confidence: 99%

A Dual Fluorescence–Spin Label Probe for Visualization and Quantification of Target Molecules in Tissue by Multiplexed FLIM–EPR Spectroscopy

et al. 2021

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Simultaneous visualization and concentration quantification of molecules in biological tissue is an important though challenging goal. The advantages of fluorescence lifetime imaging microscopy (FLIM) for visualization, and electron paramagnetic resonance (EPR) spectroscopy for quantification are complementary. Their combination in a multiplexed approach promises a successful but ambitious strategy because of spin label‐mediated fluorescence quenching. Here, we solved this problem and present the molecular design of a dual label (DL) compound comprising a highly fluorescent dye together with an EPR spin probe, which also renders the fluorescence lifetime to be concentration sensitive. The DL can easily be coupled to the biomolecule of choice, enabling in vivo and in vitro applications. This novel approach paves the way for elegant studies ranging from fundamental biological investigations to preclinical drug research, as shown in proof‐of‐principle penetration experiments in human skin ex vivo.

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A multilayered epithelial mucosa model of head neck squamous cell carcinoma for analysis of tumor-microenvironment interactions and drug development

Cited by 10 publications

References 50 publications

Primary Extracellular Matrix Enables Long-Term Cultivation of Human Tumor Oral Mucosa Models

Primary Extracellular Matrix Enables Long-Term Cultivation of Human Tumor Oral Mucosa Models

Ursolic Acid Loaded-Mesoporous Hydroxylapatite/ Chitosan Therapeutic Scaffolds Regulate Bone Regeneration Ability by Promoting the M2-Type Polarization of Macrophages

A Dual Fluorescence–Spin Label Probe for Visualization and Quantification of Target Molecules in Tissue by Multiplexed FLIM–EPR Spectroscopy

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