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Generating kidney organoids and mature renal cell types via directed iPSC differentiation

Award Number: UH2DK107344
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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¿ DESCRIPTION (provided by applicant): Generating kidney organoids and mature renal cell types via directed iPSC differentiation. Chronic kidney disease is increasing in prevalence by 6.3% per annum. Hence there is a desperate need for the development of novel treatments. The aim of the proposal is to direct the differentiation of human pluripotent stem cells towards kidney organoids containing all four key progenitor cells capable of generating a mature organ, including the nephrogenic mesenchyme, ureteric epithelium, stroma and vascular progenitors. These organoids will serve as a source of specific kidney cell types of value for cellular therapy as well as an accurate model of the organ as a whole. The proposal draws on our published data defining the methodology for generating kidney organoids and our experience in the generation of reporter iPSC lines. Results from the studies proposed will generate tools for the research community (a suite a reporter cell lines), knowledge about the development of the kidney in humans, improved methods for differentiation and proof of concept data for the application of the resulting cells in drug/nephrotoxicity screening and cellular therapy. The validity of the kidney organoids as a model of the developing organ will be interrogated using expression profiling, including single cell RNA-seq analyses. Single, double and triple fluorescent reporter iPSC lines will be generated to facilitate the subsequent isolation of specifi cell types from the organoids post differentiation. These cell types will also be characterized, providing novel information about specific kidney cell types during human development. Validating the use of organoids as a model of the developing organ will be performed so as to develop the use of organoids for drug/nephrotoxicity screening. Reporter iPSC lines will also be generated to report defined responses to injury. Nephrotoxicity screening will be performed on organoids generated using such reporter. Specific kidney cell types will be isolated from organoids via FACS and used to evaluate cellular therapy approaches for the treatment of chronic kidney injury via transplantation into immunocompromised mice. Reporter iPSC lines will also be generated to incorporate the expression of luciferase to allow for the monitoring via bioluminescence of the location of the delivered cells in live animals across time. The efficacy of delivering kidney cells derived from pluripotent stem cells into preclinical models will therefore be determined.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2018 ( Subtotal = -$9,694 )
2018	2016	MURDOCH CHILDRENS RESEARCH INSTITUTE	ROYAL CHILDRENS HOSPITAL FLEMINGTON RD	PARKVILLE		3052		AUS	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	1/24/2018	NON-COMPETING CONTINUATION	-$9,694
														Subtotal = -$9,694

Issue Date FY: 2016 ( Subtotal = $345,777 )
2016	2016	MURDOCH CHILDRENS RESEARCH INSTITUTE	ROYAL CHILDREN S HOSPITAL	PARKVILLE, VICTORIA				AUS	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	9/13/2016	NON-COMPETING CONTINUATION	$345,777
														Subtotal = $345,777

Issue Date FY: 2015 ( Subtotal = $345,600 )
2015	2015	MURDOCH CHILDRENS RESEARCH INSTITUTE	ROYAL CHILDREN S HOSPITAL	PARKVILLE, VICTORIA				AUS	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	9/23/2015	NEW	$345,600
														Subtotal = $345,600

Grand Total All Awards = $681,683

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Generating kidney organoids and mature renal cell types via directed iPSC differentiation

Award Number: UH2DK107344

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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