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Ex-Vivo Machine Perfusion To Promote Tolerance Induction in Deceased Donor Kidney Transplantation

Award Number: R21AI196804
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/23/2026
PERIOD OF PERFORMANCE END DATE: 01/31/2028

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Ex-Vivo Machine Perfusion To Promote Tolerance Induction in Deceased Donor Kidney Transplantation - PROJECT SUMMARY Establishing a reliable method to achieve allograft tolerance remains an ultimate goal in organ transplantation. We previously reported long-term immunosuppression (I.S.)-free renal allograft survival in humans after induction of only transient hematopoietic chimerism through donor bone marrow transplantation. However, a major limitation of this approach has been its inapplicability to deceased donor transplantation, as the required conditioning regimen must be initiated 5 days before combined kidney and bone marrow transplantation (CKBMT). To expand the application of our approach, it is now imperative to 1) expand the clinical applicability to deceased donor recipients and 2) improve our understanding of mechanisms whereby I.S.-free renal allograft acceptance via induction of transient mixed chimerism is achieved. Current strategies for kidneys preservation include static cold storage and hypothermic machine perfusion7, which limit preservation to a maximum of one day. Longer preservation times are associated with severe ischemia reperfusion injury (IRI) which promote acute rejection, adversely affects long- term graft survival allograft, and importantly inhibits transplant tolerance induction. To reduce IRI, our team previously targeted the integrin CD11b/CD18 (CD11b mAb), which is highly expressed on the surface of innate immune cells. These findings prompted preliminary studies, demonstrating in NHP that CD11b mAb improves hematopoietic chimerism and graft survival. In parallel, advancements in technology, and the development of sophisticated warm perfusion platforms at 22 to 34°C enabled our group and others to mitigate IRI and sustain ex-vivo perfused human kidneys in a metabolically active state for up to 5 days. Therefore, in this R21 proposal, we will 1) Explore an alternative strategy by preserving kidneys with normothermic machine perfusion (NMP) for 5 days, allowing sufficient time to complete a standard non-toxic conditioning regimen prior to CKBMT, 2) In addition to NMP we will inhibit innate immune responses with CD11b mAb, which might promote tolerance induction by mitigating IRI, and 3) Elucidate the molecular mechanisms by which NMP ± CD11b mAb affects mixed chimerism and immune tolerance. We anticipate that mitigation of IRI using NMP and CD11b mAb will allow the safe preservation of kidney grafts for 5 days, enabling the induction of mixed chimerism and achieve allograft tolerance. This will, for the first time, make tolerance induction strategies available to recipients of deceased donor allografts using clinically available technologies. This is a design-driven project with the goal of demonstrating success in a clinically relevant NHP model to justify human clinical trials / R01 application.


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 = $416,622 )
2026	2026	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	1	2/23/2026	NEW	$416,622
														Subtotal = $416,622

Grand Total All Awards = $416,622

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Ex-Vivo Machine Perfusion To Promote Tolerance Induction in Deceased Donor Kidney Transplantation

Award Number: R21AI196804

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 02/23/2026

PERIOD OF PERFORMANCE END DATE: 01/31/2028

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