Biochemist William Frazier, PhD, left, and transplant surgeon William Chapman, MD, right, have developed a method designed to prevent a major cause of donor organ injury and are testing it in animal models.
Research addresses donor organ injury
A long-standing collaboration among Washington University basic scientists and transplant surgeons to optimize donor organ health could improve transplant outcomes and potentially increase the pool of donors.
Their work addresses a major pitfall in transplantation called ischemia/ reperfusion injury — inflammatory damage that occurs when blood flow is temporarily interrupted and then restored during the transplant process.
“Ischemia/reperfusion injury happens with live and cadaver donor organs and reduces the health of the organ, and ultimately, patient outcomes. Currently there is no way to stop it,” says William Chapman, MD, the Eugene M. Bricker Professor and chief of transplant surgery.
To address the issue, Chapman and his lab are partnering with Washington University biochemist William Frazier, PhD. Several years ago, Frazier discovered a molecular chain of events involving the protein CD-47 and nitric oxide that causes damage when blood returns to the organ. To counter this pathway, Frazier has developed a CD-47 antibody blockade system.
Chapman’s lab found that the blockade reduced ischemia/reperfusion injury and improved survival in an animal liver transplantation model — an example of the later stages of T1 translational research. He is now testing the blockade and other antibody variants in other animal models.
If effective in humans, the blockade could not only improve the health of organs suitable for transplant, but potentially reduce injury in marginal organs to make them usable for transplant. The approach has important implications for the organ transplant field because of the chronic shortage of donor livers, kidneys and other organs. There are currently more than 16,000 Americans waiting for liver transplants; more than 1,500 people die every year waiting for a donated liver to become available.* More than 96,000 people are awaiting a kidney, but fewer than 17,000 people receive one each year.**
“The ultimate goal is to test the antibody blockade in human trials, assuming it continues to show promise in animal studies,” says Chapman.
If the antibody blockade is tested in clinical trials, it would represent T2 research, translating initial findings to test a hypothesis in clinical trials.
New organ preservation method may improve donor pool
Surendra Shenoy, MD, PhD, president of the Vascular Access Society of the Americas, performs a transplant.
Livers from deceased donors are a gift of life, with almost 75 percent of liver transplant recipients surviving at five years.* But many livers are not suitable for transplant — most often due to steatosis, or fatty liver — contributing to a severe shortage of these organs. So Washington University researchers are looking at whether an alternate preservation method could reduce fatty liver to make marginal donor organs healthy enough for transplant.
The Washington University and Barnes-Jewish Transplant Center is one of about 10 U.S. medical centers conducting a clinical trial of normothermic perfusion, in which the donor liver is stored at 37 C, rather than in cold storage, which goes down to 4 C. Although the trial will be in normal livers, the ultimate goal is to assess it in marginal organs.
“If this method is effective, it could be an important way for us to address donor organ shortage,” says Transplant Surgery Chief William Chapman, MD.
*U.S. Department of Health and Human Services
Highlights
- An article by Washington University transplant surgeons about dedicated facilities for retrieving donor organs was the most accessed article in the American Journal of Transplantation in 2014. Surgeon M.B. Majella Doyle, MD, MBA, was first author. The article reported a study concluding that moving organ donors from hospitals to a regional stand-alone facility with a designated operating room for organ retrieval is more efficient and lowers costs considerably. Transplant Surgery Chief William Chapman, MD, was senior author.
- Jeffrey Lowell, MD, and general surgery resident Shuddhadeb Ray, MD, were honored at the department’s first annual Patient Safety and Clinical Effectiveness Meeting for their survey on improving the department’s Surgical Morbidity and Mortality (M&M) Conference. M&M is an event all residency programs perform to review and learn from medical errors. A majority believed M&M could benefit from more faculty participation, quality-improvement focus, evidence-based literature and better-defined case selection. A follow-up survey is planned after organizers implement changes.
- Yiing Lin, MD, PhD, is developing a technique to isolate DNA from the blood of patients to test for liver cancer or recurrence of liver cancer. If effective, the technique could be an alternative to much more expensive tests such as MRI and liver biopsy currently used for diagnosis. Lin has conducted the research using liver cancer tumors sequenced at The Elizabeth H. and James S. McDonnell III Genome Institute at Washington University.