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High subzero preservation of liver for transplantation

Award Number: R01DK114506
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/17/2017
PERIOD OF PERFORMANCE END DATE: 12/31/2025

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High subzero preservation of liver for transplantation - ABSTRACT With more than five times the number of patients on the wait list than will receive a donor organ in the USA, the field of transplantation is facing a serious donor shortage crisis. Despite decades of research, a major critical bottleneck is the current preservation times for whole organs are limited to few hours of storage. Longer preservation times are required to enable global matching programs, eliminate unnecessary waste of organs, and reduce costs associated with unplanned surgeries, and are enabling for mixed-chimerism based tolerance induction protocols which require the donor organ to be kept viable for days so that recipient preconditioning can be done safely. Consequently, the focus of this application is to address a major unmet need in transplantation by prolonging the length of time organs can be kept in “suspended animation” ex vivo. Our approach is inspired by the hibernating and freeze-tolerant animals in nature. We aim to embrace and control the ice formation to achieve high subzero storage temperatures in the presence of extracellular ice, and storage durations of weeks to ultimately months. It is our hypothesis that the presence of ice in a non-injurious frozen state enables storage at lower temperatures (down to -30°C) and consequently a deeper metabolic stasis for weeks, while also enabling scale-up to human organs. In the previous funding period, we developed a new method to use ice nucleating bacteria to tightly control ice formation temperature and developed a partial freezing protocol down to -15°C that can store rat livers up to 5 days with ex vivo function, and also established a proof-of-concept in human livers. In this competing renewal application, we propose to build on our success and reach preservation temperatures down to -30°C, thus achieving suspended animation for weeks. We propose (i) to control ice formation in liver, which our prior studies demonstrated to be a key barrier; (ii) to develop targeted approaches to improve preservation of endothelium, which are at the interface of tissue and ice and are the first point of injury, and (iii) to develop a choreographed metabolic protocol to maximize ATP recovery and improve viability of the grafts for transplant.


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 = $539,879 )
2025	2025	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	9	12/23/2024	NON-COMPETING CONTINUATION	$495,967
2025	2025	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	9	12/30/2024	SUPPLEMENT FOR EXPANSION	$43,912
														Subtotal = $539,879

Issue Date FY: 2024 ( Subtotal = $661,012 )
2024	2024	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	8	1/9/2024	SUPPLEMENT FOR EXPANSION	$131,979
2024	2024	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	8	5/10/2024	NON-COMPETING CONTINUATION	$33,066
2024	2024	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	8	12/21/2023	NON-COMPETING CONTINUATION	$495,967
														Subtotal = $661,012

Issue Date FY: 2023 ( Subtotal = $594,987 )
2023	2023	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	7	1/24/2023	NON-COMPETING CONTINUATION	$551,075
2023	2023	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	7	8/31/2023	SUPPLEMENT FOR EXPANSION	$43,912
														Subtotal = $594,987

Issue Date FY: 2022 ( Subtotal = $551,075 )
2022	2022	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	6	3/29/2022	NON-COMPETING CONTINUATION	$55,108
2022	2022	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	6	12/6/2021	NON-COMPETING CONTINUATION	$495,967
														Subtotal = $551,075

Issue Date FY: 2021 ( Subtotal = $551,075 )
2021	2021	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	5	2/26/2021	COMPETING CONTINUATION	$551,075
2021	2021	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	5	8/13/2021	COMPETING CONTINUATION	$0
2021	2020	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	4	8/27/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $551,075

Issue Date FY: 2020 ( Subtotal = $384,750 )
2020	2020	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	3/5/2020	NON-COMPETING CONTINUATION	$384,750
														Subtotal = $384,750

Issue Date FY: 2019 ( Subtotal = $384,750 )
2019	2019	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	3/21/2019	NON-COMPETING CONTINUATION	$384,750
														Subtotal = $384,750

Issue Date FY: 2018 ( Subtotal = $384,750 )
2018	2018	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	2	5/7/2018	NON-COMPETING CONTINUATION	$38,475
2018	2018	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	3/19/2018	NON-COMPETING CONTINUATION	$346,275
														Subtotal = $384,750

Issue Date FY: 2017 ( Subtotal = $384,750 )
2017	2017	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	7/14/2017	NEW	$384,750
														Subtotal = $384,750

Grand Total All Awards = $4,437,028

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High subzero preservation of liver for transplantation

Award Number: R01DK114506

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/17/2017

PERIOD OF PERFORMANCE END DATE: 12/31/2025

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