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Therapeutic vascularization to support repair of damaged salivary glands

Award Number: R01DE030103
ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/01/2022
PERIOD OF PERFORMANCE END DATE: 03/31/2027

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Therapeutic vascularization to support repair of damaged salivary glands - Project Summary Damage to salivary glands is a devastating condition – identification of therapies to promote regeneration of these important organs is imperative. Great progress is being made in engineering and transplantation of salivary gland epithelium. A major remaining hurdle in gland engineering is the need to establish a functional vasculature, which is essential for survival of any replacement tissue in vivo. In addition to essential support, therapeutic angiogenesis also stimulates healing of non-vascular tissue. This study will characterize methods of promoting vascularization in regenerating salivary gland tissues. Using mice as a pre-clinical model system, we will evaluate two distinct therapeutic approaches – individually and in combination – to promote vascularization and regeneration of damaged glands. One therapeutic approach involves implantation of an exogenous vascular cell milieu as a method to enhance formation of functional blood vessel networks. The other approach, which may be effective when used in conjunction with implanted cells, or on its own, will involve systemic delivery of a drug with potential to stimulate angiogenesis. The therapeutic potentials of the of the two approaches will be evaluated separately and in combination in vivo in mice in a biopsy wound healing model. Cellular and molecular events of vascular assembly associated with each therapy will be defined using cell culture assays in vitro. For implantation of vascular cells, we will use a cell milieu of stromal vascular fraction derived from adipose (AdSVF). The AdSVF cell milieu has real advantages as a cell source. It includes many cell types needed to form functional blood vessel networks (endothelial, pericytes, vascular smooth muscle, fibroblasts) it reduces inflammation to promote regeneration of parenchymal tissue, it is readily available for self-donation, and, importantly, has proven safe for clinical use. As an adjunct to implanted AdSVF, or as a stand-alone vascularizing therapeutic, we will also test the ability of a systemic pharmacologic agent Tazarotene to stimulate formation of functional vascular networks. Tazarotene is a synthetic retinoid. Its vascular promoting activity is consistent with the action of natural retinoids, including vitamin A and its derivative retinoic acid, which are essential for vascular assembly in vivo. This project will identify methods to promote functional vasculature in regenerating salivary glands. Resulting knowledge can be used to enhance success of therapies aimed at repairing salivary epithelium, thereby advancing the field toward developing effective therapies for patients suffering from salivary gland damage.


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 = $371,688 )
2025	2025	UNIVERSITY OF LOUISVILLE	2301 S 3RD ST	LOUISVILLE	KY	40208	JEFFERSON	USA	Oral Diseases and Disorders Research	001	4	5/8/2025	NON-COMPETING CONTINUATION	$37,169
2025	2025	UNIVERSITY OF LOUISVILLE	2301 S 3RD ST	LOUISVILLE	KY	40208	JEFFERSON	USA	Oral Diseases and Disorders Research	000	4	3/7/2025	NON-COMPETING CONTINUATION	$334,519
														Subtotal = $371,688

Issue Date FY: 2024 ( Subtotal = $364,254 )
2024	2024	UNIVERSITY OF LOUISVILLE	2301 S 3RD ST	LOUISVILLE	KY	40208	JEFFERSON	USA	Oral Diseases and Disorders Research	001	3	6/19/2024	NON-COMPETING CONTINUATION	$29,735
2024	2024	UNIVERSITY OF LOUISVILLE	2301 S 3RD ST	LOUISVILLE	KY	40208	JEFFERSON	USA	Oral Diseases and Disorders Research	000	3	3/21/2024	NON-COMPETING CONTINUATION	$334,519
														Subtotal = $364,254

Issue Date FY: 2023 ( Subtotal = $371,688 )
2023	2023	UNIVERSITY OF LOUISVILLE	2301 S 3RD ST	LOUISVILLE	KY	40208	JEFFERSON	USA	Oral Diseases and Disorders Research	000	2	3/22/2023	NON-COMPETING CONTINUATION	$371,688
														Subtotal = $371,688

Issue Date FY: 2022 ( Subtotal = $371,391 )
2022	2022	UNIVERSITY OF LOUISVILLE	2301 S 3RD ST	LOUISVILLE	KY	40208	JEFFERSON	USA	Oral Diseases and Disorders Research	000	1	3/17/2022	NEW	$371,391
														Subtotal = $371,391

Grand Total All Awards = $1,479,021

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Therapeutic vascularization to support repair of damaged salivary glands

Award Number: R01DE030103

ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/01/2022

PERIOD OF PERFORMANCE END DATE: 03/31/2027

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