Penn Advances Transplant Research
As with all areas of clinical medicine, new, robust research is needed to constantly push the science of transplantation forward. In addition to being one of the busiest transplant centers in the country, the Penn Transplant Institute is a premier research establishment. Penn physicians, surgeons and scientists are nationally recognized researchers as well as clinicians.
Multiple National Institutes of Health (NIH)-supported trials are currently under way for each organ transplanted at Penn– heart, kidney, liver, lung and pancreas.
One of the most exciting transplant research developments at Penn is the study of organ dysfunction and rejection in transplant recipients. In many cases, when a patient receives an organ transplant, the body’s immune system treats the new organ as a foreign threat and attacks it. For this reason, standard post-transplant treatment involves immunosuppression or anti-rejection therapy to lower the body’s immune reaction, allowing the new organ to function.
Abraham Shaked, MD, PhD, director of the Penn Transplant Institute, received NIH funding to study the genetics of organ donors with hopes of using the molecular structure in donated organs to predict organ failure in the period immediately following transplant surgery. Exploring pathways of injury can identify an organ at risk of failure and lead to improved treatment strategies. Currently, 10 to 25 percent (depending on the organ) of all transplant recipients experience abnormal function of the organ that can have an impact on long-term organ rejection.
These studies are extended to determine biomarkers of rejection in blood and urine of organ recipients. Testing urine samples after kidney transplantation can help in the diagnosis of rejection without the need for a biopsy, and even predict rejection allowing successful treatment to prevent long-lasting injury to the transplanted kidney.
Penn is leading this multi-center study.
Mechanical Assist Devices Provide Bridge to Transplant
The mechanical assist device program at the Hospital of the University of Pennsylvania is an integral component of the Penn Transplant Institute. As one of the busiest heart transplant programs in the region, a variety of mechanical assist devices are used to support the sickest patients waiting for a transplant – each year, these devices help up to 30 percent of waiting individuals survive long enough to receive a new heart. Some are even able to return home while waiting.
Penn cardiac transplant researchers are nationally recognized experts in heart surgery, heart failure, transplant care and cardiac-assist device technology. Penn Transplant Institute has been at the forefront of mechanical assist device technology research. Penn participated in the groundbreaking 1975 multi-center study, funded by the National Institutes of Health (NIH) that first explored sustained heart bypass for patients with devastating heart injuries. Penn Transplant Institute was the first in the Philadelphia region to send a patient home with a Left Ventricular Assist Device (LVAD) system – and among the first in the country to study new fully implantable device technology.
In 2007, Penn became the first hospital in the Northeastern United States to implant the temporary Total Artificial Heart (TAH-t). This technology is used as a bridge to transplant for patients waiting for a donor heart who have both sides of their heart failing, do not respond to other treatments and are at imminent risk of death. Research has shown that patients receiving the TAH-t have almost twice the survival rate as patients who received standard ventricular assist devices. Penn researchers are now studying a new portable device driver which would allow TAH-t recipients to return home while they wait for transplant.
“TAH-t is an exciting and valuable device to have when the situation requires its use,” said Mariell Jessup, MD, medical director of heart failure and transplantation at Penn. “Access to this kind of technology represents a strong commitment from Penn to support these vital programs.”
Penn heart transplant specialists are also taking a closer look at improving methods of immunosuppression for transplant recipients. Ongoing research includes the physiologic effects of cardiac rejection, the role of tissue matching in heart transplantation and dynamic cardiomyoplasty.
Living Donor Liver Transplantation
The Penn Transplant Institute is one of nine centers participating in an NIH-funded multi-center study of adult-to-adult living donor liver transplantation.
The Adult-to-Adult Living Donor Liver Transplant Cohort Study (A2ALL) investigates the experience of a group of patients eligible for living donor liver transplantation, and focuses on the factors influencing outcomes of living donor liver transplants for both donors and recipients. Researchers will compare outcomes of this new procedure with the outcomes for patients who receive livers from deceased donors.
Liver transplantation is an accepted and successful treatment option for patients suffering from severe liver disease. The number of patients awaiting transplant has grown dramatically while the supply of deceased donor organs has remained roughly the same. This can mean a longer wait and an increased possibility of death for patients waiting for a liver transplant.
The anatomy of the liver allows for partial donation in that there are specific liver segments with their own blood supply that can be divided and transplanted into another individual. The liver also has the unique ability to regenerate within weeks of removing a segment. These characteristics of the liver encouraged transplant surgeons to pursue living donation of the liver.
The Penn Transplant Institute performed its first adult-to-adult living donor liver transplant in 1999. The liver transplant team, led by Kim Olthoff, MD, is currently studying liver function and liver regeneration in transplant recipients and donors following surgery, specifically the effects of anti-rejection therapy and gene therapy. The results of this extended study will give liver transplant patients and potential donors solid information about the risks and benefits of this innovative and sometimes controversial procedure.
Dr. Shaked is also researching the withdrawal of immunosuppression in deceased donor transplant recipients. Here, the aim is to slowly remove anti-rejection therapy until the patient no longer needs the medications. The study’s asserted goal is that 20 percent of all liver transplant recipients may not need immunosuppression therapy for the rest of their lives.
Islet Transplantation: Leading The Way In Treating Diabetes Research
Research into the transplantation of islet cells holds promise for many patients with type 1 diabetes. The immune system of type 1 diabetics destroys the insulin-producing islet cells located in the pancreas. Until recently, the best treatment options for many type 1 diabetics were regular insulin injections and, in severe cases, a pancreas transplant.
Islet cell transplantation involves taking functioning islet cells from a donor and transplanting them into the diabetic patient. A successful transplant results in the recipient’s pancreas accepting the new islet cells and allowing them to produce insulin. When successful, the transplant frees the patient from the routine of daily insulin injections.
Under the direction of Ali Naji, MD, the Penn Center for Islet Transplantation was established in 1999 as a collaborative effort between the University of Pennsylvania and the Juvenile Diabetes Research Foundation. Dr. Naji and a multi-disciplinary team of surgeons, endocrinologists, immunologists and radiologists monitor and evaluate islet cell function in transplant patients.
Ongoing Research Leads to Better Treatments
The Penn kidney and pancreas transplant programs have been continuously funded for research by NIH for more than 30 years. In addition to islet cell transplantation studies headed by Dr. Naji, Dr. Olthoff is studying kidney transplantation in HIV patients and subsequent differences in the body’s immunological responses.
Penn’s lung transplant team is researching new ways to prevent primary graft dysfunction –that is, failure of the transplanted lung to function normally. Penn pulmonary scientists study protein levels and other biomarkers in patients before and after transplant surgery to identify the most ideal protein level going into surgery that will decrease the risk of primary organ failure. If successful, this study will facilitate the development of a protein level test for patients going into lung transplant surgery so the patient’s protein levels could be adjusted, giving the best possible chance for normal lung function following transplantation.
More people are surviving end-stage organ disease than ever before. Penn patients, even “high risk” patients, with severe heart, kidney, liver and lung disease have experienced the success of Penn research studies that have been translated into progressive clinical care. As one of the top transplant programs in the country, the Penn Transplant Institute continues to be on the cutting edge of innovative treatment options for transplantation.
|
