Cross-circulation platform for prolonged extracorporeal support of donor organs for transplantation

This platform provides cross-circulation of blood from a living host to maintain homeostasis of organs for extended preservation and injury repair prior to transplantation.

Unmet Need: A method of extending the viable lifetime of organs prior to transplantation

The demand for transplantable organs increases every year, and supply is further limited by the short time period for which donor organs remain viable using current support systems. As such, techniques for extending extracorporeal organ lifetime are critically needed. Conventional methods of extracorporeal organ support rely on circulation of perfusion fluids in closed systems, which lack metabolic clearance and therefore the ability to maintain physiologic homeostasis, resulting in the accumulation of toxic metabolites and waste products that have deleterious effects on organ function and viability. This problem limits the extended support time to 6-12 hours, which is still prohibitively short for medical intervention (e.g., to treat infections or improve organ function by clearing inflammation) in an extracorporeal setting. Notably, current support methods do not allow repair of organ injury prior to transplant.

The Technology: Cross-circulation platform to enhance preservation of donor organs 

This technology allows prolonged extracorporeal support of an organ, tissue, or bioengineered graft by cross-circulation via connection of a host (e.g., animal or organ transplant recipient). In lieu of constantly re-circulating the same fluid, this system utilizes cross-circulation of host blood to ensure the maintenance of homeostasis outside the body, increasing the time of organ viability from hours to days and potentially weeks. The extended duration of extracorporeal support will allow for intervention and recovery of otherwise unusable donor organs, thereby significantly expanding the pool of transplantable donor organs as well as providing a means for modifying the donor organ for improved long-term outcomes. This technology has been validated in a swine model for human and swine lungs and livers.

The technology was covered by the:

• New York Times
• New Scientist
• Nature Medicine
• Nature
• The Lancet

The following images are of human donor lungs recovered over 24 hours of cross-circulation, taken at 0 hours, 12 hours, and 24 hours:

Applications:

• Ex vivo maintenance of extracorporeal donor organs

• Recovery of sub-optimal donor organs

• Conditioning prior to organ transplant

• Xenotransplantation studies

• Disease modeling

• Drug testing

Advantages: 

• Prolonged organ preservation times

• Increased pool of organs for transplant

• Maintenance of organ function and normal physiology

• Medical intervention on donor organ

• Enhanced patient outlook for recipients of donated organs

Lead Inventor: 

Gordana Vunjak-Novakovic, Ph.D.

Patent Information: 

Patent Status

Related Publications:

• Hozain A, O’Neill J, Pinezich M, Tipograf Y, Donocoff R, Cunningham K, Tumen A, Fund K, Ukita R, Simpson M, Reimer J, Ruiz E, Queen D, Stokes J, Cardwell N, Talackine J, Kim J, Snoeck HW, Chen YW, Romanov A, Marboe C, Griesemer A, Guenthart B, Bacchetta M, Vunjak-Novakovic G. “Xenogeneic cross-circulation for extracorporeal recovery of injured human lungs” Nat Med. 2020 Jul; 26(7):1102-1113.
• Hozain A, Tipograf Y, Pinezich M, Cunningham K, Donocoff R, Queen D, Fung K, Marboe C, Guenthart B, O'Neill J, Vunjak-Novakovic G, Bacchetta M. “Multi-day maintenance of extracorporeal lungs using cross-circulation with conscious swine” J Thorac Cardiovasc Surg. 2019 Oct 17.
• Guenthart BA, O’Neill JD, Kim J, Queen D, Chicotka S, Fung K, Simpson M, Donocoff R, Salna M, Marboe C, Cunningham K, Halligan SP, Wobma HM, Hozain AE, Romanov A, Vunjak-Novakovic G, Bacchetta M. “Regeneration of severely damaged lungs using an interventional cross-circulation platform” Nat Comm. 2019 May 7; 10(1).
• Guenthart BA, O’Neill JD, Kim J, Fung K, Vunjak-Novakovic G, Bacchetta M. “Cell Replacement in human lung bioengineering” J Heart Lung Transplant. 2019 Feb; 38(2): 215 224.
• Guenthart BA, Chen YW, Bacchetta M. “New insights and therapeutic targets: Lung injury and disease” J Thorac Cardiovasc Surg. 2019 Jan; 157(1): 416-420.
• O’Neill JD, Guenthart BA, Kim J, Chicotka S, Queen D, Fung K, Marboe C, Romanov A, Huang SXL, Chen YW, Snoeck HW, Bacchetta M, Vunjak-Novakovic G. “Cross-circulation for extracorporeal support and recovery of the lung” Nat Biomed Eng. 2017 Mar 6; 1.

Tech Ventures Reference:

• IR CU16207, CU18416, CU19009, CU19020, CU19051, CU19143

• Licensing Contact: Beth Kauderer