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11.5.3 Bioengineering Replacement Kidney Tissue
Finally, the capacity to make many of the founding cell types required for the for-
mation of a functional adult kidney provides a source of cells for use in the bioengi-
neering of a replacement organ. While it would appear inconceivable that we might
be able to regenerate an organ of the size and complexity of the human kidney, and
certainly impossible to do so with the tight architectural accuracy of the original
organ, protocols allowing the generation of kidney organoids from human pluripo-
tent stem cells for the first time provide an expandable and renewable source of
material from which to bioengineer some form of replacement organ. There have
already been a number of bioengineering attempts to generate kidney tissue prior to
this point in time. These have included the recellularisation of decellularised kidney
scaffolds (Song et al. 2013 ; Bonandrini et al. 2014 ; Caralt et al. 2015 ), seeding of
primary cells along hollow fibres (Jansen et al. 2016 ), and the generation of a renal
assist device designed to work in parallel with dialysis (Humes et al. 2004 ). To date,
the cells used for these attempts have either been primary isolates of human cells
acquired from cadaveric tissue (Humes et al. 2004 ; Song et al. 2013 ; Jansen et al.
2016 ) or undifferentiated cell types, including hPSC (Bonandrini et al. 2014 ). With
the accurate patterning of iPSC to specific kidney cell types, either fully matured or
in a progenitor state, organoid production would represent an approach that would
allow increased scale-up and improved reproducibility.
11.6 Conclusion
In this chapter, we have described the development of approaches for the generation
of complex human kidney organoids from human pluripotent stem cell sources.
These kidney organoids represent models of the cells and structures forming within
the developing organ, including the patterning nephrons, collecting duct epithelium
and surrounding interstitium. The capacity to pattern pluripotent cells in a dish to
simultaneously induce multiple interacting cell types able to self-organise accord-
ing to the morphogenetic principles at work within the developing foetus is quite
remarkable. The opportunities that arise with such an approach are substantial;
however, there remains a long way to go.
Acknowledgements ML is a National Health and Medical Research Council Senior Principal
Research Fellow. Her work is supported by the NHMRC, Australian Research Council, Royal
Children’s Hospital Foundation, Kidney Health Australia and the National Institutes of Health,
USA. TF is an NHMRC Postgraduate Scholar and holds an RACP/NHMRC Award for Excellence.
JY-CS holds a University of Melbourne Research Scholarship. MCRI is supported by the Victorian
Government’s Operational Infrastructure Support Program.
M.H. Little et al.