Organ-on-a-Chip Glomerulus and Nephrotube Model

Lead Research Organisation: University of Manchester
Department Name: Materials

Abstract

The current model for drug development requires the need for extensive animal studies. These can take years to complete and results may not accurately predict response in humans. One way forward is to develop in vitro models that mimic whole organ function, the so called organ-on-a-chip concept. The current state of the artfor the organ-on-a-chip is based on the microculture of populations of a single cell type or two different (but separated) cell populations in coculture within a device. This concept has been successfully used to create mimics of lung, kidney and gut tissue. However, this design is 2-dimensional and cannot accurately mimic organ structure. This follow on fund proposal will develop the organ-on-a-chip concept further by building a better model of organ tissue building on prior BBSRC funded work manipulating sheets of cells. This will be used to develop improved models of a kidney-on-a-chip with applications in drug toxicity testing and drug development.

Publications

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Holmes AM (2017) Rising to the challenge: applying biofabrication approaches for better drug and chemical product development. in Biofabrication

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Loewenhardt W (2017) Integrating Cell Sheets for Organ-on-a-chip Applications in Procedia CIRP

 
Description We have been able to successfully grow sheets of kidney glommerular endothelial cells and podocytes on surfaces that enable whole intact sheets to be removed and inserted into a bioreactor. We have successfully constructed a bioreactor for the project.
Exploitation Route This will depend on further work in progress but if successful this couls be used to reduce the use of laboratory animals in toxicity trials. We have received funding from industry to continue the study.
Sectors Pharmaceuticals and Medical Biotechnology
 
Description BBSRC Industrial CASE
Amount £127,776 (GBP)
Funding ID BB/P504348/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 09/2017 
End 10/2020
 
Description University of Manchester Charitable Donation
Amount £2,500 (GBP)
Organisation University of Manchester 
Sector Academic/University
Country United Kingdom
Start 01/2017 
End 08/2017
 
Description BBSRC Industrial CASE studentship: Glaxo Smith Klein 
Organisation GlaxoSmithKline (GSK)
Department GlaxoSmithKline Medicines Research Centre
Country United Kingdom 
Sector Private 
PI Contribution GSK are interested in developing in vitro models of organs for a drug discovery purposes. We have developed a novel concept and GSK are interested in assessing its applicability.
Collaborator Contribution Support for a studentship
Impact Too early in project for outputs
Start Year 2017
 
Description Imaging of Biological Printing for High Throughput Applications (IAA Proof of Concept Award with FFEI Ltd.) 
Organisation FFEI
Country United Kingdom 
Sector Private 
PI Contribution The University of Manchester is a pioneer in the field of cell printing and has been working in the field for over 10 years with EPSRC funding supporting Ph.D. studentships, A Post-Doctoral Research Fellowship(Dr. R.E. Saunders), EPSRC grant support with the most recent to Derby being EP/L012022/1 and BBSRC support e.g. BB/N01250X/1. It has also featured in the Doctoral Training Programme in Regenerative Medicine and is an important component of the Henry Royce Institute Biomaterials Theme EP/P025021/1 and EP/R00661X/1. Manchester has considerable experience in printing a range of cells and exploring the physical science aspects of the process, e.g. influence of shear flow and acoustic effects on cell viability, and machine and process development to optimise viability. The integration of cell printing with high throughput analysis remains unexplored commercially. The proposed project will exploit the several years of experience accumulated in Manchester on successful cell deposition, placement, patterning for applications in tissue engineering, medical engineering and organ-on-a-chip technology. This will provide basic understanding for the integration of a bioprinter with the imaging technology skills of the industrial partner.
Collaborator Contribution FFEI has significant, existing commercial expertise in digital scanning for whole-slide imaging in pathology and manufacturing of digital inkjet engines. This project will investigate, for the first time, combining high throughput cell printing (Manchester) and high-throughput scanning analysis techniques (FFEI) for application to drug discovery, tissue engineering and medical diagnostics.High-throughput printing of cells and biological material into discrete formations, followed by highly variable over-printing and simultaneous digital analysis, offers an all-in-one solution that is currentlynot available. This presents opportunity for FFEI to integrate and manufacture project outputs to approach new markets. The IAA proof of concept data produced will lead to a future novel and commercially viable life science device that can be developed further by FFEI.
Impact Early stages of collaboration - no outputs yet
Start Year 2020
 
Title Multilayer sheet of cells used in in-vitro assay, such as toxicity assay that measures transfer of substance across multilayer sheet of cells, comprise layer of endothelial cell, and adjacent layer of podocytes 
Description Technology Focus/Extension Abstract: TECHNOLOGY FOCUS - BIOLOGY - Preferred Conditions: The endothelial cells are glomerular endothelial cells. The multilayer sheet of cells comprises extracellular matrix disposed between cell layers. The multilayer sheet of cells are provided on a support surface. The multilayer sheet of cells are detachable from support surface without enzymatic treatment, where support surface is temperature responsive support surface. The cell layers are confluent cell layers. The multilayer sheet of cells are tolerant of flow conditions. The multilayer sheet of cells are impervious to proteins of more than 100kDa. The in vitro cell culture comprises extracellular matrix disposed between the cell layers. The in vitro cell culture is provided on a support surface. The support surface is a surface from which the multilayer sheet of cells is detachable without enzymatic treatment. The device comprises liquid/fluid permeable support for multilayer sheet of cells. The device comprises liquid/fluid inlet to compartment adjacent to layer of endothelial cells, and liquid/fluid outlet from compartment adjacent to layer of podocytes. The device comprises compartment having renal epithelial cells. The compartment having renal epithelial cells is in liquid/fluid communication with compartment adjacent to layer of podocytes. The multilayer sheet of cells are produced by providing a layer of endothelial cells that is glomerular endothelial cells, layering podocytes into layer of endothelial cells, and culturing cells in vitro. The method involves contacting endothelial cells or glomerular endothelial cells with support surface, and culturing the cells on support surface in vitro. The method involves detaching multilayer sheet of cells from support surface. The multilayer sheet of cells are produced by providing a layer of podocyte cells, providing layer of endothelial cells, placing layer of endothelial cells into layer of podocyte cells, or placing layer of podocyte cells onto layer of endothelial cells, and culturing the cells in vitro to produce multilayer sheet of cells. The layer of podocyte cells and layer of endothelial cells are layered on a support surface. The bilayer sheet of cells consist of layer of endothelial cells, layer of podocytes and extracellular matrix disposed between cell layers. 
IP Reference WO2016207654 
Protection Patent application published
Year Protection Granted 2016
Licensed Commercial In Confidence
Impact Further collaboratiuon with industry
 
Description Interview by BBC World Service (Arabic) 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact Laboratory visit and description of research into Bioprinting at the University of Manchester. Equipment funded by the award was discussed.
Year(s) Of Engagement Activity 2018
 
Description Stand at Science Festival 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Stand at Blue Dot Science and Music Festival. 3D printing demonstration, Hands on demonstration printing conductors, Audience mainly children and young adults, team interacted and fielded questions in 3D printing and printed electronics.
Year(s) Of Engagement Activity 2019
 
Description Stand at Science Festival (Blue Dot festival, July 2019) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Activity was a stand at science festival showing how materials fabrication methods could be used to make biological constructs. Introduced concept of an organ on a chip. Some hands on demonstrations for participants. Audience general public with focus on High school Age children.
Year(s) Of Engagement Activity 2019