Modulation of coagulation factors for organ transplantation.
Organ transplants are commonly used for treatment of organ failure, however, there is a major shortage in donor organs, and the difference between supply and demand continues to grow every year. This causes organ recipients to wait for prolonged periods of time before a transplant can be found, and often no matched transplants are found, resulting in death of many patients every year. For example, 12.5% of the U.S. liver recipients died on the waiting list in 2009. Therefore, there is an urgent need to find alternative sources for transplants. Pig embryonic tissues represent an attractive option for organ transplantation. A major challenge after transplantation is achieving optimal organ size. The present technology demonstrates that factors of the coagulation cascade have a novel role in organ size control.
Organ size control is a major parameter in transplantation of organs from a xenogeneic origin, since not all of the xenogeneic organs are at the size fit for human use. In the present technology it was discovered that a difference in the functionality of one gene in the recipients, namely coagulation Factor VIII, has a major impact on the final size attained by different embryonic pig tissues (spleen, pancreas, and liver) upon transplantation into mice. Interrogation of other factors along the coagulation cascade that are triggered by Factor VIII suggests that the enzyme thrombin is likely to be the actual mediator of this novel checkpoint of organ size control. All of these insights can help in controlling the size of the implanted organ after transplantation.