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Transplantation of MHC Homozygous Vascular Progenitors in Primates

Award Number: U01HL134655
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/20/2016
PERIOD OF PERFORMANCE END DATE: 05/31/2025

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Transplantation of MHC Homozygous Vascular Progenitors in Primates - Project Summary/Abstract for, “Transplantation of MHC homozygous vascular progenitors in primates.” For tissue engineered arteries, the use of patient specific iPS cells would be severely limited by time constraints and cost. Banking iPS cells from rare individuals homozygous for HLA alleles has been proposed as a strategy to allow economies of scale, while still reducing rejection of iPS cell-derived transplanted tissues. Only a few hundred such cell lines would provide matches for the majority of the U.S. population, and the Waisman Clinical Biomanufacturing facility here on the University of Wisconsin has already produced cGMP HLA homozygous iPS cell lines. However, the immunological value of such an approach remains untested in an animal model with an immune system similar to the human immune system. Here we will use a unique population of MHC defined cynomolgus monkeys to test the immune response to MHC homozygous cynomolgus iPS cell-derived vascular cells transplanted to MHC haploidentical recipients. Using the MHC defined cynomolgus monkeys, we will use a limb ischemia model to determine the ability of iPS cell-derived arterial endothelial cells to contribute to collateral circulation when transplanted by themselves, in combination with iPS cell-derived smooth muscle cells, or when combined into a fully tissue engineered artery. A central premise of this proposal is that properly specified early arterial endothelial cells will robustly recruit, expand, and mature endogenous or co-transplanted smooth muscle cell progenitors to increase arteriogenesis in vivo, and that these arterial endothelial cells will be critical to producing tissue engineered arteries ex vivo that remain functional long after transplantation. The final goal of this proposal is to produce cGMP vascular progenitors from HLA homozygous human iPS cell lines for the pre-clinical animal studies required to file an IND for critical limb ischemia. With extensive human and primate pluripotent stem cell expertise, a strong bioengineering department, a National Primate Research Center with an MHC typing facility, and a GMP cell manufacturing facility, the environment at the University of Wisconsin is uniquely suited for completing the goals of this proposal.


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: 2024 ( Subtotal = $0 )
2024	2022	THE MORGRIDGE INSTITUTE FOR RESEARCH, INC.	330 N ORCHARD ST	MADISON	WI	53715	DANE	USA	Cardiovascular Diseases Research	000	7	4/10/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2022	THE MORGRIDGE INSTITUTE FOR RESEARCH, INC.	330 N ORCHARD ST	MADISON	WI	53715	DANE	USA	Cardiovascular Diseases Research	000	7	8/17/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $1,148,048 )
2022	2022	THE MORGRIDGE INSTITUTE FOR RESEARCH, INC.	330 N ORCHARD ST	MADISON	WI	53715	DANE	USA	Cardiovascular Diseases Research	002	7	5/20/2022	NON-COMPETING CONTINUATION	$1,148,048
2022	2021	MORGRIDGE INSTITUTE FOR RESEARCH, INC., THE	330 N ORCHARD ST	MADISON	WI	53715	DANE	USA	Cardiovascular Diseases Research	001	6	3/2/2022	NON-COMPETING CONTINUATION	$0
2022	2021	MORGRIDGE INSTITUTE FOR RESEARCH, INC., THE	330 N ORCHARD ST	MADISON	WI	53715	DANE	USA	Cardiovascular Diseases Research	000	6	10/18/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,148,048

Issue Date FY: 2021 ( Subtotal = $1,154,922 )
2021	2021	MORGRIDGE INSTITUTE FOR RESEARCH, INC., THE	330 N ORCHARD ST	MADISON	WI	53715	DANE	USA	Cardiovascular Diseases Research	000	6	6/2/2021	NON-COMPETING CONTINUATION	$1,154,922
														Subtotal = $1,154,922

Issue Date FY: 2020 ( Subtotal = $1,175,384 )
2020	2020	MORGRIDGE INSTITUTE FOR RESEARCH, INC., THE	330 N ORCHARD ST	MADISON	WI	53715	DANE	USA	Cardiovascular Diseases Research	000	5	6/4/2020	NON-COMPETING CONTINUATION	$1,175,384
														Subtotal = $1,175,384

Issue Date FY: 2019 ( Subtotal = $1,191,694 )
2019	2019	MORGRIDGE INSTITUTE FOR RESEARCH, INC., THE	330 N ORCHARD ST	MADISON	WI	53715	DANE	USA	Cardiovascular Diseases Research	000	4	5/15/2019	NON-COMPETING CONTINUATION	$1,191,694
														Subtotal = $1,191,694

Issue Date FY: 2018 ( Subtotal = $1,205,577 )
2018	2018	MORGRIDGE INSTITUTE FOR RESEARCH, INC., THE	330 N ORCHARD ST	MADISON	WI	53715	DANE	USA	Cardiovascular Diseases Research	000	3	5/11/2018	NON-COMPETING CONTINUATION	$1,205,577
														Subtotal = $1,205,577

Issue Date FY: 2017 ( Subtotal = $887,713 )
2017	2017	MORGRIDGE INSTITUTE FOR RESEARCH, INC., THE	330 N ORCHARD ST	MADISON	WI	53715	DANE	USA	Cardiovascular Diseases Research	000	2	6/2/2017	NON-COMPETING CONTINUATION	$887,713
														Subtotal = $887,713

Issue Date FY: 2016 ( Subtotal = $903,597 )
2016	2016	THE MORGRIDGE INSTITUTE FOR RESEARCH INC	330 NORTH ORCHARD STREET	MADISON	WI	53715	DANE	USA	Cardiovascular Diseases Research	000	1	9/20/2016	NEW	$903,597
														Subtotal = $903,597

Grand Total All Awards = $7,666,935

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Transplantation of MHC Homozygous Vascular Progenitors in Primates

Award Number: U01HL134655

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

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

PERIOD OF PERFORMANCE START DATE: 09/20/2016

PERIOD OF PERFORMANCE END DATE: 05/31/2025

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