Tuesday, November 4, 2025 11/4/2025

Biomaterials for delivery and maintenance of tip endothelial cells

Award Number: R21HL172096
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/15/2023
PERIOD OF PERFORMANCE END DATE: 11/30/2026

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Biomaterials for delivery and maintenance of tip endothelial cells - PROJECT SUMMARY The mortality rates for patients with critical limb ischemia (CLI) are 15-40%, depending on the treatment. Moreover, the quality of life for surviving patients remains severely reduced. Limb revascularization focused on limb rescue is critical to saving lives and life quality. Cell therapy strategies currently under investigation inject a variety of progenitor cells into ischemic tissue with varying levels of success. However, no one has examined the ability of angiogenic tip-specific endothelial cells (ECs) to promote revascularization in an ischemic limb. We hypothesize that angiogenic ECs that contain tip ECs will more robustly revascularize ischemic limbs compared with nonangiogenic ECs. The proposed studies will use highly expandable pluripotent stem cells as the starting cell source and derive tip and non-tip cell-containing ECs from human induced pluripotent stem (iPS) cells. We will then compare the ability of tip ECs versus non-tip ECs to rescue the muscle in a hind-limb ischemic mouse model. For delivery, we employ spatially nanopatterned collagen biomaterial scaffolds to enhance cell survival after transplantation into the ischemic limb. Lastly, we will incorporate placental growth factor (PIGF) mRNA delivery from aligned nanopatterned collagen biomaterials to support the release of PlGF protein for maintaining the angiogenic phenotype of tip ECs, and/or directing in vivo the differentiation of stalk-to-tip ECs. We expect these studies to show that angiogenic tip-specific ECs, not only integrate into and support current vasculature in the ischemic limb, but also initiate the growth of new blood vessels, faster re-establishment of tissue perfusion, and reproducibly rescue the ischemic limb.


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: 2025 ( Subtotal = $327,736 )
2025	2025	UNIVERSITY OF CALIFORNIA, MERCED	5200 N LAKE RD	MERCED	CA	95343	MERCED	USA	Cardiovascular Diseases Research	002	2	9/25/2025	SUPPLEMENT FOR EXPANSION	$145,760
2025	2025	UNIVERSITY OF CALIFORNIA, MERCED	5200 N LAKE RD	MERCED	CA	95343	MERCED	USA	Cardiovascular Diseases Research	000	2	11/9/2024	NON-COMPETING CONTINUATION	$181,976
2025	2024	UNIVERSITY OF CALIFORNIA, MERCED	5200 N LAKE RD	MERCED	CA	95343	MERCED	USA	Cardiovascular Diseases Research	001	1	9/25/2025	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $327,736

Issue Date FY: 2024 ( Subtotal = $315,140 )
2024	2024	UNIVERSITY OF CALIFORNIA, MERCED	5200 N LAKE RD	MERCED	CA	95343	MERCED	USA	Cardiovascular Diseases Research	002	1	9/20/2024	SUPPLEMENT FOR EXPANSION	$0
2024	2024	UNIVERSITY OF CALIFORNIA, MERCED	5200 N LAKE RD	MERCED	CA	95343	MERCED	USA	Cardiovascular Diseases Research	001	1	9/4/2024	SUPPLEMENT FOR EXPANSION	$77,635
2024	2024	UNIVERSITY OF CALIFORNIA, MERCED	5200 N LAKE RD	MERCED	CA	95343	MERCED	USA	Cardiovascular Diseases Research	000	1	12/11/2023	NEW	$237,505
														Subtotal = $315,140

Grand Total All Awards = $642,876

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Biomaterials for delivery and maintenance of tip endothelial cells

Award Number: R21HL172096

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 12/15/2023

PERIOD OF PERFORMANCE END DATE: 11/30/2026

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