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Synthetic Mesenchymal Stem Cell Niches for Vascular Therapy

Award Number: R01HL119371
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/15/2013
PERIOD OF PERFORMANCE END DATE: 07/31/2025

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Synthetic Mesenchymal Stem Cell Niches for Vascular Therapy - Project Summary A huge and unmet clinical need is associated with hemodialysis vascular access dysfunction, which is currently considered to be one of the most challenging forms of clinical vascular grafting. The high failure rates associated with all types of dialysis vascular access, including arteriovenous fistulae and arteriovenous graft, result in significant morbidity, mortality and economic cost. Despite the magnitude of this clinic problem, no effective solutions are available. The end-stage renal disease and other health conditions of hemodialysis patients present a hostile milieu, such as uremia, inflammation and flow disturbance caused by small and/or non-compliant vessel, around the vascular access, which account for, at least partially, the access failure. The central hypothesis for this proposal is that precision cell niches, developed under hemodialysis-relevant conditions and when applied to the clinical setting of dialysis vascular access, prevent dialysis access failure. To test this hypothesis, we will introduce cell-protective, regenerative signals in the precision cell niches, which functionalize mesenchymal stem cells (MSCs) to override the hostile milieu impact and orchestrate the arterial regeneration, leading to patent, robust vascular access. This project will use our novel biomaterials platform, which allows both the cell niche and the niche-containing structure to be tailored using clinical inputs such as uremia, blood flow, vessel compliance and diameter, with a goal of optimizing targeted arterial regeneration to reduce access failure. To pursue the research goal, three aims are proposed here. AIM 1 focuses on incorporating the precision cell niches into a peri-vascular wrap and determining its effect on the arterialization of arteriovenous fistula under simulated hemodialysis conditions. AIM 2 seeks to establish and spatially integrate distinct precision cell niche designs to promote arteriovenous graft arterialization. AIM 3 will evaluate how the precision niche design can assist MSC-based arterial regeneration for vascular access in a diseased swine model. If successful, the precision vascular access platforms developed here could transform traditional clinical care paradigms for dialysis vascular access. We envision that in the near future, nephrologists could have the access to a range of vascular access devices derived from precision cell niche designs.


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: 2026 ( Subtotal = -$18,073 )
2026	2023	THE REGENTS OF THE UNIVERSITY OF COLORADO	3100 MARINE ST	BOULDER	CO	80309	BOULDER	USA	Cardiovascular Diseases Research	000	10	2/17/2026	NON-COMPETING CONTINUATION	-$18,073
														Subtotal = -$18,073

Issue Date FY: 2023 ( Subtotal = $590,882 )
2023	2023	REGENTS OF THE UNIVERSITY OF COLORADO, THE	3100 MARINE ST STE 481 572 UCB	BOULDER	CO	80309	BOULDER	USA	Cardiovascular Diseases Research	000	10	7/17/2023	NON-COMPETING CONTINUATION	$546,302
2023	2023	REGENTS OF THE UNIVERSITY OF COLORADO, THE	3100 MARINE ST STE 481 572 UCB	BOULDER	CO	80309	BOULDER	USA	Cardiovascular Diseases Research	001	10	8/23/2023	SUPPLEMENT FOR EXPANSION	$44,580
														Subtotal = $590,882

Issue Date FY: 2022 ( Subtotal = $776,456 )
2022	2022	REGENTS OF THE UNIVERSITY OF COLORADO, THE	3100 MARINE ST STE 481 572 UCB	BOULDER	CO	80309	BOULDER	USA	Cardiovascular Diseases Research	002	9	7/22/2022	SUPPLEMENT FOR EXPANSION	$82,683
2022	2022	REGENTS OF THE UNIVERSITY OF COLORADO, THE	3100 MARINE ST STE 481 572 UCB	BOULDER	CO	80309	BOULDER	USA	Cardiovascular Diseases Research	001	9	7/21/2022	NON-COMPETING CONTINUATION	$655,671
2022	2022	REGENTS OF THE UNIVERSITY OF COLORADO, THE	3100 MARINE ST STE 481 572 UCB	BOULDER	CO	80309	BOULDER	USA	Cardiovascular Diseases Research	000	8	3/4/2022	SUPPLEMENT FOR EXPANSION	$38,102
														Subtotal = $776,456

Issue Date FY: 2021 ( Subtotal = $655,671 )
2021	2021	REGENTS OF THE UNIVERSITY OF COLORADO, THE	3100 MARINE ST STE 481 572 UCB	BOULDER	CO	80309	BOULDER	USA	Cardiovascular Diseases Research	000	8	8/2/2021	NON-COMPETING CONTINUATION	$655,671
														Subtotal = $655,671

Issue Date FY: 2020 ( Subtotal = $625,601 )
2020	2020	REGENTS OF THE UNIVERSITY OF COLORADO, THE	3100 MARINE ST STE 481 572 UCB	BOULDER	CO	80309	BOULDER	USA	Cardiovascular Diseases Research	004	7	8/13/2020	NON-COMPETING CONTINUATION	$625,601
2020	2019	REGENTS OF THE UNIVERSITY OF COLORADO, THE	3100 MARINE ST STE 481 572 UCB	BOULDER	CO	80309	BOULDER	USA	Cardiovascular Diseases Research	003	6	8/12/2020	COMPETING CONTINUATION	$0
2020	2019	REGENTS OF THE UNIVERSITY OF COLORADO, THE	3100 MARINE ST STE 481 572 UCB	BOULDER	CO	80309	BOULDER	USA	Cardiovascular Diseases Research	002	6	4/23/2020	COMPETING CONTINUATION	$558,377
2020	2019	REGENTS OF THE UNIVERSITY OF COLORADO, THE	3100 MARINE ST STE 481 572 UCB	BOULDER	CO	80309	BOULDER	USA	Cardiovascular Diseases Research	001	6	4/9/2020	COMPETING CONTINUATION	-$558,377
2020	2017	REGENTS OF THE UNIVERSITY OF COLORADO, THE	3100 MARINE ST STE 481 572 UCB	BOULDER	CO	80309	BOULDER	USA	Cardiovascular Diseases Research	000	5	2/22/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $625,601

Issue Date FY: 2019 ( Subtotal = $558,377 )
2019	2019	REGENTS OF THE UNIVERSITY OF COLORADO, THE	3100 MARINE ST STE 481 572 UCB	BOULDER	CO	80309	BOULDER	USA	Cardiovascular Diseases Research	000	6	8/26/2019	COMPETING CONTINUATION	$558,377
2019	2019	REGENTS OF THE UNIVERSITY OF COLORADO, THE	3100 MARINE ST STE 481 572 UCB	BOULDER	CO	80309	BOULDER	USA	Cardiovascular Diseases Research	001	6	8/29/2019	COMPETING CONTINUATION	$0
														Subtotal = $558,377

Issue Date FY: 2017 ( Subtotal = $370,811 )
2017	2017	REGENTS OF THE UNIVERSITY OF COLORADO, THE	3100 MARINE ST., RM 479 572 UCB	BOULDER	CO	80303	BOULDER	USA	Cardiovascular Diseases Research	000	5	6/19/2017	NON-COMPETING CONTINUATION	$370,811
														Subtotal = $370,811

Issue Date FY: 2016 ( Subtotal = $363,742 )
2016	2016	UNIVERSITY OF COLORADO, OFFICE OF CONTRACTS & GRANTS	CAMPUS BOX B-19	BOULDER	CO	80309	BOULDER	USA	Cardiovascular Diseases Research	000	4	6/28/2016	EXTENSION WITH OR WITHOUT FUNDS	$363,742
														Subtotal = $363,742

Issue Date FY: 2015 ( Subtotal = $360,294 )
2015	2015	UNIVERSITY OF COLORADO, OFFICE OF CONTRACTS & GRANTS	CAMPUS BOX B-19	BOULDER	CO	80309	BOULDER	USA	Cardiovascular Diseases Research	000	3	7/13/2015	NON-COMPETING CONTINUATION	$360,294
														Subtotal = $360,294

Issue Date FY: 2014 ( Subtotal = $359,188 )
2014	2014	UNIVERSITY OF COLORADO, OFFICE OF CONTRACTS & GRANTS	CAMPUS BOX B-19	BOULDER	CO	80309	BOULDER	USA	Cardiovascular Diseases Research	000	2	7/1/2014	NON-COMPETING CONTINUATION	$359,188
														Subtotal = $359,188

Issue Date FY: 2013 ( Subtotal = $361,841 )
2013	2013	UNIVERSITY OF COLORADO, OFFICE OF CONTRACTS & GRANTS	CAMPUS BOX B-19	BOULDER	CO	80309	BOULDER	USA	Cardiovascular Diseases Research	000	1	8/9/2013	NEW	$361,841
														Subtotal = $361,841

Grand Total All Awards = $5,004,790

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Synthetic Mesenchymal Stem Cell Niches for Vascular Therapy

Award Number: R01HL119371

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/15/2013

PERIOD OF PERFORMANCE END DATE: 07/31/2025

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