Three-dimensional organotypic matrices from alternative collagen sources as pre-clinical models for cell biology

Organotypic co-cultures bridge the gap between standard two-dimensional culture and mouse models. Such assays increase the fidelity of pre-clinical studies, to better inform lead compound development and address the increasing attrition rates of lead compounds within the pharmaceutical industry, whi...

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Vydané v:Scientific reports Ročník 7; číslo 1; s. 16887 - 15
Hlavní autori: Conway, James R. W., Vennin, Claire, Cazet, Aurélie S., Herrmann, David, Murphy, Kendelle J., Warren, Sean C., Wullkopf, Lena, Boulghourjian, Alice, Zaratzian, Anaiis, Da Silva, Andrew M., Pajic, Marina, Morton, Jennifer P., Cox, Thomas R., Timpson, Paul
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: London Nature Publishing Group UK 04.12.2017
Nature Publishing Group
Predmet:
13/51
631/67/70
631/80/79/750
Animal models
Animals
Atomic force microscopy
Cancer
Cell culture
Cell Culture Techniques - methods
Cell Line
Cell Proliferation - drug effects
Cell Survival - drug effects
Coculture Techniques
Collagen
Collagen (type I)
Collagen - chemistry
Collagen - isolation & purification
Extracellular Matrix - metabolism
Gefitinib - pharmacology
Humanities and Social Sciences
Humans
Invasiveness
Macropodidae - metabolism
Mice
Microscopy
Microscopy, Atomic Force
multidisciplinary
Pharmaceutical industry
Rats
Scanning electron microscopy
Science
Science (multidisciplinary)
Tendons - metabolism
Tumor cell lines
Ultrastructure
ISSN:2045-2322, 2045-2322
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Abstract Organotypic co-cultures bridge the gap between standard two-dimensional culture and mouse models. Such assays increase the fidelity of pre-clinical studies, to better inform lead compound development and address the increasing attrition rates of lead compounds within the pharmaceutical industry, which are often a result of screening in less faithful two-dimensional models. Using large-scale acid-extraction techniques, we demonstrate a step-by-step process to isolate collagen I from commercially available animal byproducts. Using the well-established rat tail tendon collagen as a benchmark, we apply our novel kangaroo tail tendon collagen as an alternative collagen source for our screening-ready three-dimensional organotypic co-culture platform. Both collagen sources showed equal applicability for invasive, proliferative or survival assessment of well-established cancer models and clinically relevant patient-derived cancer cell lines. Additional readouts were also demonstrated when comparing these alternative collagen sources for stromal contributions to stiffness, organization and ultrastructure via atomic force microscopy, second harmonic generation imaging and scanning electron microscopy, among other vital biological readouts, where only minor differences were found between the preparations. Organotypic co-cultures represent an easy, affordable and scalable model to investigate drug responses within a physiologically relevant 3D platform.
AbstractList Organotypic co-cultures bridge the gap between standard two-dimensional culture and mouse models. Such assays increase the fidelity of pre-clinical studies, to better inform lead compound development and address the increasing attrition rates of lead compounds within the pharmaceutical industry, which are often a result of screening in less faithful two-dimensional models. Using large-scale acid-extraction techniques, we demonstrate a step-by-step process to isolate collagen I from commercially available animal byproducts. Using the well-established rat tail tendon collagen as a benchmark, we apply our novel kangaroo tail tendon collagen as an alternative collagen source for our screening-ready three-dimensional organotypic co-culture platform. Both collagen sources showed equal applicability for invasive, proliferative or survival assessment of well-established cancer models and clinically relevant patient-derived cancer cell lines. Additional readouts were also demonstrated when comparing these alternative collagen sources for stromal contributions to stiffness, organization and ultrastructure via atomic force microscopy, second harmonic generation imaging and scanning electron microscopy, among other vital biological readouts, where only minor differences were found between the preparations. Organotypic co-cultures represent an easy, affordable and scalable model to investigate drug responses within a physiologically relevant 3D platform.
Organotypic co-cultures bridge the gap between standard two-dimensional culture and mouse models. Such assays increase the fidelity of pre-clinical studies, to better inform lead compound development and address the increasing attrition rates of lead compounds within the pharmaceutical industry, which are often a result of screening in less faithful two-dimensional models. Using large-scale acid-extraction techniques, we demonstrate a step-by-step process to isolate collagen I from commercially available animal byproducts. Using the well-established rat tail tendon collagen as a benchmark, we apply our novel kangaroo tail tendon collagen as an alternative collagen source for our screening-ready three-dimensional organotypic co-culture platform. Both collagen sources showed equal applicability for invasive, proliferative or survival assessment of well-established cancer models and clinically relevant patient-derived cancer cell lines. Additional readouts were also demonstrated when comparing these alternative collagen sources for stromal contributions to stiffness, organization and ultrastructure via atomic force microscopy, second harmonic generation imaging and scanning electron microscopy, among other vital biological readouts, where only minor differences were found between the preparations. Organotypic co-cultures represent an easy, affordable and scalable model to investigate drug responses within a physiologically relevant 3D platform.Organotypic co-cultures bridge the gap between standard two-dimensional culture and mouse models. Such assays increase the fidelity of pre-clinical studies, to better inform lead compound development and address the increasing attrition rates of lead compounds within the pharmaceutical industry, which are often a result of screening in less faithful two-dimensional models. Using large-scale acid-extraction techniques, we demonstrate a step-by-step process to isolate collagen I from commercially available animal byproducts. Using the well-established rat tail tendon collagen as a benchmark, we apply our novel kangaroo tail tendon collagen as an alternative collagen source for our screening-ready three-dimensional organotypic co-culture platform. Both collagen sources showed equal applicability for invasive, proliferative or survival assessment of well-established cancer models and clinically relevant patient-derived cancer cell lines. Additional readouts were also demonstrated when comparing these alternative collagen sources for stromal contributions to stiffness, organization and ultrastructure via atomic force microscopy, second harmonic generation imaging and scanning electron microscopy, among other vital biological readouts, where only minor differences were found between the preparations. Organotypic co-cultures represent an easy, affordable and scalable model to investigate drug responses within a physiologically relevant 3D platform.
ArticleNumber 16887
Author Conway, James R. W.
Murphy, Kendelle J.
Zaratzian, Anaiis
Boulghourjian, Alice
Morton, Jennifer P.
Warren, Sean C.
Da Silva, Andrew M.
Herrmann, David
Vennin, Claire
Wullkopf, Lena
Pajic, Marina
Cox, Thomas R.
Cazet, Aurélie S.
Timpson, Paul
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Publisher Nature Publishing Group UK
Nature Publishing Group
Publisher_xml – name: Nature Publishing Group UK
– name: Nature Publishing Group
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Snippet Organotypic co-cultures bridge the gap between standard two-dimensional culture and mouse models. Such assays increase the fidelity of pre-clinical studies, to...
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StartPage 16887
SubjectTerms 13/51
631/67/70
631/80/79/750
Animal models
Animals
Atomic force microscopy
Cancer
Cell culture
Cell Culture Techniques - methods
Cell Line
Cell Proliferation - drug effects
Cell Survival - drug effects
Coculture Techniques
Collagen
Collagen (type I)
Collagen - chemistry
Collagen - isolation & purification
Extracellular Matrix - metabolism
Gefitinib - pharmacology
Humanities and Social Sciences
Humans
Invasiveness
Macropodidae - metabolism
Mice
Microscopy
Microscopy, Atomic Force
multidisciplinary
Pharmaceutical industry
Rats
Scanning electron microscopy
Science
Science (multidisciplinary)
Tendons - metabolism
Tumor cell lines
Ultrastructure
Title Three-dimensional organotypic matrices from alternative collagen sources as pre-clinical models for cell biology
URI https://link.springer.com/article/10.1038/s41598-017-17177-5
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Volume 7
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