Technological advancements extend survival of transplanted hearts across species

April 28, 2014, American Association for Thoracic Surgery

Cardiac transplantation is the treatment of choice for end stage heart failure. According to the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health, approximately 3,000 people in the US are on the waiting list for a heart transplant, while only 2,000 donor hearts become available each year. Therefore for the cardiac patients currently waiting for organs, mechanical assist devices are the only options available. These devices, however, are not perfect and have issues with power supplies, infection, and both clotting and hemolysis.

Transplantation using an animal organ, or xenotransplantation, has been proposed as a valid option to save valuable human lives. Muhammad M. Mohiuddin, MD, of the Cardiothoracic Surgery Research Program at the NHLBI, and co-investigators have now developed techniques to overcome some of the immunologic roadblocks that hinder successful xenotransplantation using genetically engineered pigs as a source of donor organs. Pigs were chosen because their anatomy is compatible with that of humans and they have a rapid breeding cycle, among other reasons.

As the result of recent improvements in technology for genetic modification of pigs, genes that are immunogenic for humans have been eliminated ('knocked out") and several human genes have been added to the pig genome. Grafts from these genetically engineered (GE) pigs are less likely to be seen as foreign, thus reducing the immune reaction against them. These modifications should also allow transplants utilizing lower amounts of toxic immunosuppressive drugs.

"These recent scientific developments in the field of genetic engineering, along with the generation of novel target specific immune suppression, and their favorable impact on organ and cellular transplantation, may instill a new ray of hope for thousands of patients waiting for human donor organs," comments Dr. Mohiuddin.

The NHLBI group was fortunate to have access to GE pigs through close collaboration with Revivicor, Inc. Experiments using these GE pig hearts, transplanted in the abdomen of baboons along with their native hearts, were designed to study the usefulness of these GE pigs along with several new target-specific immunosuppressive agents in prolonging the graft survival. Through the combination of a pig heart with certain gene modifications, with drugs suppressing both T and B cell immune responses, investigators were able to prolong the graft survival in baboons to over one year. This unique achievement by the NIH laboratory is twice as long as previously reported.

The long-term surviving grafts exhibit normal histology (cellular architecture) and contractility. The researchers' next step is to use hearts from the same GE pigs with the same immunosuppression utilized in the current experiments to test their ability to provide full life support by replacing the original baboon heart.

"Based on the data from long-term surviving grafts, we are hopeful that we will be able to repeat our results in the life-supporting model. If successful, this method could change the current transplant paradigm, eliminating the shortage of donor organs including hearts, livers, kidneys, intestine, as well as insulin producing cells for treatment of diabetes," concludes Dr. Mohiuddin. He is presenting the results of this research at the 94th AATS Annual Meeting in Toronto, ON, Canada on April 28, 2014.

Explore further: Could deceased heart attack victims expand donor pool?

More information: "Genetically Engineered Pigs And Target-Specific Immunomodulation Provide Significant Graft Survival and Hope for Clinical Cardiac Xenotransplantation," by Muhammad M. Mohiuddin, MD, Avneesh K. Singh, PhD, Philip C. Corcoran, MD, Robert F. Hoyt, DVM, Marvin L. Thomas III, DVM, David Ayares, PhD, Keith A. Horvath, MD. Presentation at the 94th AATS Annual Meeting. April 26-30, 2014. Toronto, ON, Canada, during the Adult Cardiac Surgery Session on April 28, 2:20 PM ET. aats.org/annualmeeting

Related Stories

Could deceased heart attack victims expand donor pool?

November 11, 2013
Researchers from the U.K. suggest that using organs from donors after circulatory death (DCD) who also suffered a previous cardiac arrest out of the hospital environment could expand the pool of available livers for transplant. ...

More than bacon: Genetic alterations in pig tissue may allow for human transplantation

June 30, 2011
A sizzling genetic discovery by Chinese scientists may one day allow pig tissue to be transplanted successfully into humans. Their research presented in the Journal of Leukocyte Biology represents a major step forward toward ...

Beating new life into a heart transplant

July 10, 2013
Human hearts which are not used each year because they are deemed unsuitable for an organ transplant could get a second chance to save a life, with the help of new research taking place in the North East.

Transplant expert dispels organ donation misconceptions

April 21, 2014
(HealthDay)—Misconceptions prevent many people from agreeing to donate their organs and potentially save a life, according to a transplant expert.

New clues found to preventing lung transplant rejection

February 25, 2014
Organ transplant patients routinely receive drugs that stop their immune systems from attacking newly implanted hearts, livers, kidneys or lungs, which the body sees as foreign.

Xenotransplantation as a therapy for type 1 diabetes: Pig beta cells show great promise in an animal model

April 23, 2012
Transplantation of a whole pancreas or isolated insulin-producing beta cells are the only therapy to cure type I diabetes. However, the shortage of organ donors limits this approach to only few patients. LMU researchers have ...

Recommended for you

New study finds that surgeons under stress make more mistakes in the operating room

December 17, 2018
A new study reveals that during stressful moments in the operating room, surgeons make up to 66 percent more mistakes on patients. Using a technology that captured the electrical activity of a surgeon's heart, researchers ...

Surgical adhesions can be treated, prevented in mice

November 28, 2018
A cellular culprit—as well as a possible treatment—for a common, sometimes life-threating post-surgical complication has been identified by researchers at the Stanford University School of Medicine.

Cost and weight-loss potential matter most to bariatric surgery patients

November 28, 2018
A JAMA Surgery study found that patients are likely to base their weight loss surgery choice on expected out-of-pocket costs, and how much weight they can lose—not risk of complications or recovery time.

Treating spinal pain with replacement discs made of 'engineered living tissue' moves closer to reality

November 21, 2018
For the first time, bioengineered spinal discs were successfully implanted and provided long-term function in the largest animal model ever evaluated for tissue-engineered disc replacement. A new Penn Medicine study published ...

Screening for colorectal cancer spares male patients from intense treatments

November 21, 2018
While screening for colorectal cancer does not reduce mortality, it does reduce the need for chemotherapy and emergency surgeries among male patients, according to a recent Finnish study.

Rapid response inpatient education boosts use of needed blood-thinning drugs

November 16, 2018
A new study designed to reach hospitalized patients at risk shows that a "real-time" educational conversation, video or leaflet can lower the missed dose rates of drugs that can prevent potentially lethal blood clots in their ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.