A tissue engineering approach to reduce animal use in renal development and renal organ replacement technology

This project has two aims; (1) to replace animals in an important field of research and (2) to develop a superior culture system for renal tissue engineering. Research into renal regeneration and renal replacement therapy is growing rapidly, driven by urgent clinical need. It is clear, however, that advance will depend on a better understanding of signalling and lineage in normal renal development. These are being investigated in a variety of ways, all of which use animals, either in vivo or by organ culture of kidneys isolated from embryos. The organ culture system has proved particularly useful, but is still limited in its ability to allow manipulation of gene expression. This project aims to produce cell lines that can give rise to specific components of the kidney in an organotypic setting, and can reconstitute a whole embryonic kidney in combination. Based on our existing systems, we will produce these cell lines both by conditional immortalization of cells from embryonic kidneys and by sorting and culture of ES cell derivatives. We will assess the fates available to each line in an organotypic context and will assess their ability to produce renal structures, up to a whole kidney, in novel tissue engineering culture systems based on our current state-of-the-art. This project brings together the expertise of three laboratories to achieve a significant advance in both the 3Rs and in renal regeneration and replacement by tissue engineering.

Related Content

Davies JA (2015) Biological techniques: Kidney tissue grown from induced stem cells. Nature 526(7574): 512-3 doi:10.1038/nature15639

Davies JA (2015) Self-organized Kidney Rudiments: Prospects for Better in vitro Nephrotoxicity Assays. Biomarker Insights 10(Suppl 1): 117-23 doi:10.4137/BMI.S20056

Tai G, Hohenstein P, Davies JA (2013) FAK-Src signalling is important to renal collecting duct morphogenesis: discovery using a hierarchical screening technique. Biol Open 2(4):416-23 doi:10.1242/bio.20133780

Davies JA (2012) Fetal Organ Culture. Replacing Animal Models: A Practical Guide to Creating and Using Culture-Based Biomimetic Alternatives 81-87 doi: 10.1002/9781119940685.ch8

Davies JA (2012) Potential Advantages of Using Biomimetic Alternatives. Replacing Animal Models: A Practical Guide to Creating and Using Culture-Based Biomimetic Alternatives 1-11 doi:10.1002/9781119940685.ch1

Davies JA, Unbekandt M, Ineson J, Lusis M, Little MH (2012) Dissociation of embryonic kidney followed by re-aggregation as a method for chimeric analysis.Methods Mol Biol 886:135-46 doi:10.1007/978-1-61779-851-1_12.

Davies JA and Unbekandt M (2012) siRNA-mediated RNA interference in embryonic kidney organ culture. Methods Mol Biol 886:295-303 doi:10.1007/978-1-61779-851-1_26.

Chang CH and Davies JA (2012) An improved method of renal tissue engineering, by combining renal dissociation and reaggregation with a low-volume culture technique, results in development of engineered kidneys complete with loops of Henle. Nephron Exp Nephrol. 121(3-4):e79-85. doi:10.1159/000345514

Tai G and Davies JA (2012) Hierarchical Screening of Pathways: Using Cell and Organ Cultures to Reduce use of Transgenic Mice. Replacing Animal Models: A Practical Guide to Creating and Using Culture-Based Biomimetic Alternatives 123-136 doi: 10.1002/9781119940685.ch12 

Tai G, Hohenstein P, Davies JA (2012) Making immortalized cell lines from embryonic mouse kidney. Methods Mol Biol 886:165-71. doi:10.1007/978-1-61779-851-1_15

Ganeva V, Unbekandt M, Davies JA (2011) An improved kidney dissociation and reaggregation culture system results in nephrons arranged organotypically around a single duct system. Organogenesis 7(2):83-7. doi:10.4161/org.7.2.14881.

Lee WC, Hough MT, Liu W, Ekiert R, Lindström NO, Hohenstein P, Davies JA (2010) Dact2 is expressed in the developing ureteric bud/collecting duct system of the kidney and controls morphogenetic behavior of collecting duct cells. Am J Physiol Renal Physiol 299(4):F740-51. doi:10.1152/ajprenal.00148.2010.

Sebinger DD, Unbekandt M, Ganeva VV, Ofenbauer A, Werner C, Davies JA (2010) A novel, low-volume method for organ culture of embryonic kidneys that allows development of cortico-medullary anatomical organization.PLoS One 5(5):e10550. doi:10.1371/journal.pone.0010550.

Unbekandt M and Davies JA (2010) Dissociation of embryonic kidneys followed by reaggregation allows the formation of renal tissues. Kydney Int 77(5):407-16. doi:10.1038/ki.2009.482

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Project grant

Status:

Closed

Principal investigator

Professor Jamie Davies

Institution

University of Edinburgh

Grant reference number

G0700480/1

Award date:

Mar 2008 - Sep 2011

Grant amount

£364,036