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Use of Recombinant Human Activated Protein C to Enhance the Cytoprotective and Anticoagulant Effects of Tissues Transgenic for Human Endothelial Protein C Receptor

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Overview

Organ transplantation is limited by a critical shortage of donor organs. To address this shortage, clinicians have developed transgenic pigs to express human proteins that regulate rejection, inflammation, and thrombosis. Pigs expressing the human Endothelial Protein C Receptor (hEPCR) is a recent advancement in the field and activated via the endogenous Activated Protein C (aPC) to suppress inflammation that may lead to transplant rejection. UMB researchers have developed a method to pretreat hEPCR transgenic tissue with aPC before exposure to human blood to decrease the incidence of subsequent thrombosis, reduces endothelial damage, and decreases thrombin-induced vascular permeability.

This invention is a method to enhance the viability of transplanted tissues and organs by pretreating hEPCR transgenic tissues with exogenous recombinant human aPC, an endogenous enzyme that suppresses inflammation through cytoprotective mechanisms via its binding to hEPCR, to stimulate cytoprotective and anti-thromboticeffects before exposure to cellular and tissue insult.

 

 

Applications

The unavailability of organs to meet the demand for transplantation has resulted in a major organ shortage crisis. In the United States, a new name is added every 10 minutes to the organ transplant waiting list. Only 33,611 transplants were performed in 2016, and 22 people die on average each day while waiting for a transplant. The organs that are most in demand are the kidneys (82.9%), liver (12.3%), heart (3.4%) and lungs (1.2%). There is a tremendous demand for new methods to address this growing crisis

Advantages

Improved survival of Xenogeneic transplant tissues and organs

Stage of Development

This technology has been tested in GalKO.hCD46.hEPCR porcine cultures and tissues using a cellular perfusion assay to model thrombosis under physiological shear flow conditions.

(As of 8//31/2017)- MEW

Licensing Potential

UMB seeks to develop and commercialize via an exclusive or non-exclusive license agreement and/or sponsored research with a company active in the area.

Contact Info

Office of Technology Transfer
620 W Lexington St., 4th Floor
Baltimore, MD 21201
Email: [email protected]
Phone: (410) 706-2380