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Therapeutic expansion of beige adipose tissue with optimized in situ hydrogel implants

Award Number: F31EB025736
ORGANIZATION: NATIONAL INSTITUTE Of BIOMEDICAL IMAGING & BIOENGINEERING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 11/16/2018
PERIOD OF PERFORMANCE END DATE: 11/15/2020

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Therapeutic expansion of beige adipose tissue with optimized in situ hydrogel implants - Project Summary/Abstract To combat the obesity epidemic, we will need to develop new biomedical tools more capable of targeting the root cause; namely caloric excess and increased fat deposition. The expansion of beige adipose tissues has been found to be highly effective as a therapeutic for combating metabolic disorders such as obesity in small animal models. To this end, my lab with our collaborators have generated an implantable synthetic organ that can be used clinically to increase the amount of beige adipose tissue in patients. This synthetic organ, termed beige adipose tissue – matrix assisted cell transplant (BAT-MACT), is built from adipose-derived mesenchymal stem cells (ADMSC) and short peptide adhesion ligand-conjugated hyaluronic acid-based hydrogels optimized to reinforce beige adipocyte differentiation and function. This system has been shown to promote metabolic health and reverse the negative effects of high fat diets. However, the BAT-MACT relies on isolating stem cells from a patient’s white adipose tissues, thus requiring a surgical procedure such as liposuction to collect source material. This proposal outlines steps aimed at streamlining the procedure and reducing the patient burden/costs associated with this therapeutic tool. My goal with this grant is to refine the BAT-MACT into a single injectable by developing a novel biomaterial that will recruit and differentiate the requisite ADMSC populations to generate a functional synthetic organ that is thermogenically active. To accomplish this, my first aim will be to screen a library of extracellular matrix ligands and growth factors know to exert chemoattractive effects on isolated stromal vascular fraction ADMSC using well characterized migration and attachment assays. Components found to promote recruitment and proliferation of preadipocyte populations will be then carried into the second aim which will seek to determine whether the factors identified will promote the desired thermogenically-derived physiological effects, namely increased heat production and lipid metabolism, of the ADMSC in vitro. Optimizations to the hydrogel found to promote recruitment and differentiation will then be applied to animal model systems. Aim three will explore whether or not these optimized hydrogel networks can be implanted adjacent to adipose depots in vivo and then orchestrate the recruitment and differentiation to promote the development of a synthetic beige adipose tissues, while maintaining minimal recruitment of the host’s immune system. These implants will be examined for their ability to promote metabolic health compared to our previously characterized BAT-MACT technology. This new iteration of bioengineered beige adipose tissue will be titled beige adipose tissue - matrix-assisted in situ implant (BAT-MAISI). This novel bioengineered tissue will be a powerful tool for clinically combating the obesity epidemic and will expand our overall understanding of how to craft and control bioengineered organs for therapeutic purposes.


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: 2023 ( Subtotal = -$2,274 )
2023	2020	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	2	10/17/2022	NON-COMPETING CONTINUATION	-$2,274
														Subtotal = -$2,274

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2020	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	002	2	9/29/2022	NON-COMPETING CONTINUATION	$7,021
2022	2020	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	001	2	4/22/2022	NON-COMPETING CONTINUATION	-$7,021
2022	2018	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	1	4/22/2022	NEW	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $40,483 )
2020	2020	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 220	BERKELEY	CA	94710	ALAMEDA	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	2	11/27/2019	NON-COMPETING CONTINUATION	$40,483
														Subtotal = $40,483

Issue Date FY: 2018 ( Subtotal = $39,991 )
2018	2018	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	2150 SHATTUCK AVE RM 313	BERKELEY	CA	94704	ALAMEDA	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	1	9/12/2018	NEW	$39,991
														Subtotal = $39,991

Grand Total All Awards = $78,200

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Therapeutic expansion of beige adipose tissue with optimized in situ hydrogel implants

Award Number: F31EB025736

ORGANIZATION: NATIONAL INSTITUTE Of BIOMEDICAL IMAGING & BIOENGINEERING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 11/16/2018

PERIOD OF PERFORMANCE END DATE: 11/15/2020

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