Exploring the State of the Science in the Field of Regenerative Medicine Challenges of and Opportunities for Cellular Therapies: Proceedings of a Workshop (2017) / Chapter Skim
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6 Renal Tissue
6 Renal Tissue
Pages 55-64
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From page 55... ...
• Blastocyst complementation and xenotransplantation are promising concepts, but they are still very early in the discovery phase. Under standing the scientific basis and complex ethical issues related to both concepts will require years of additional research before they reach the clinic.
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From page 56... ...
The only alternative treatment to dialysis is kidney transplantation, which costs less in the long term and improves life expectancy, but is less feasible because there are not enough donor kidneys available to meet the needs of a growing number of patients. More than 100,000 ESRD patients are on the transplant list (National Kidney Foundation, 2016)
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From page 57... ...
In the immediate future, these organoids hold promise for several applications, including disease modeling, toxicity testing for drugs, and drug discovery, Humphreys said. While organoids hold the potential to improve the quality and accuracy of research models in the near future, there is also hope that scientists will eventually be able to grow functional kidney tissue intended for clinical applications in vitro using the technique established to develop organoids.
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From page 58... ...
. A study conducted in mice with severe combined immunodeficiency found that the transplantation of pig pancreatic islet cells into the mice resulted in limited PERV infections with no related symptoms.
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From page 59... ...
With current CRISPR technology, the potential to create pig embryos that lack kidneys and other target organs is increasingly feasible, Humphreys said, and the injection of human iPS cells into the CRISPR-edited blastocysts could result in the development of pig chimeras that produce human organs for transplant into patients in need. The immunorejection of the xenogenic organ in the host animal and the potential for organs derived of a mix of host animal and xenogenic tissues remain technical challenges (Kemter and Wolf, 2015)
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From page 60... ...
POLYCYSTIC KIDNEY DISEASE Polycystic kidney disease (PKD) is a fatal, monogenic disease and is the fourth leading cause of renal replacement therapy, said David Baron, the chief scientific officer of the PKD Foundation.
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From page 61... ...
. Another way to detect PKD is through genetic testing, which may be appropriate if there is a family history of PKD or if magnetic resonance imaging or ultrasound imaging shows an uncertain diagnosis of PKD (National Kidney Foundation, 2016c)
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From page 62... ...
; • autologous genetically "corrected" stem cell infusion; • the infusion of exosomes containing corrected forms of the polycystin-1 protein or mRNA; and • implants of autologous genetically corrected kidney organoids or non-immunologic hybrid kidneys made from autologous corrected kidney cells seeded onto a non-immunologic bioengineered scaffold. Most of these potential therapies are years away from the clinic, Baron emphasized, though he noted that because treating PKD involves nephron regeneration or cell repair, advances in this area may be generalizable to other renal diseases or other ciliopathies.
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From page 63... ...
Right now, he said, it is possible to create about 200 nephrons in a small organoid, but in the future it will be possible to scale up production to produce the million nephrons that are present in an adult kidney. Hoshizaki added that investment in creating kidney organoids may be fruitful not only as a potential therapeutic organ, but as a research and assay tool.
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From page 64... ...
To date, this approach has not shown success in humans, Humphreys responded. However, the fact that other species -- particularly fish -- can grow new nephrons indicates that perhaps the developmental signaling pathways could be reactivated in mammals and result in new nephrons.
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