All Eyes on Transplantation
When doctors performed the first organ transplantation in 1954, transferring a man’s kidney to his ailing twin, the miraculous procedure ushered in a new era of medicine. Millions of lives have since been saved. Today’s leading-edge technology brings both new promise and new obstacles. We asked 14 experts, from surgeons to stem cell scientists, nurses to pharmacists — and a patient — what they would change about organ transplantation. Read on to learn how they are approaching this ever-changing field.
Demand outstrips supply
One of the biggest problems facing transplant patients and doctors is the shortage of donated organs. Whether you’re waiting for a kidney, heart, pancreas, liver, or lung, demand outstrips supply — and patients sometimes die while languishing on a national waiting list that adds a new name every 10 minutes. The number of donated hearts in the U.S. has barely changed in 30 years, hovering at around 2,000 annually — far short of the 50,000 to 100,000 needed. The 5,000 donated livers don’t come close to covering the 17,000 patients waiting for one. The problem is sure to become more acute as the population ages, multiplying the number of people who eventually may need a new organ. At the same time, the donor pool keeps shrinking, albeit for a positive reason: Advances in safety, such as helmet and seatbelt laws, make accidents — the leading source of donated organs — less likely to be fatal. But Cedars-Sinai experts have ideas to help overcome this deficit.
Michelle M. Kittleson, MD, PhD, cardiologist:
TRANSPLANT ORGANS WITH MINOR IMPERFECTIONS.
“We should consider transplanting organs that meet most but not all criteria for transplantation,” Kittleson says. Unlike in the U.S., in Europe it is standard practice to use, if need be, an “extended-criteria” organ — one that is not pristine. “A heart with minor imperfections might give a patient 10 or more good years,” she says. “It’s better than dying from end-stage heart failure. If U.S. programs were more open to less-than-perfect hearts, we could save more lives.”
Kittleson is a cardiologist at the Cedars-Sinai Heart Institute. Her areas of expertise include advanced heart failure, transplant cardiology, and cardiovascular disease.
Tram T. Tran, MD, hepatologist:
TREAT UNDERLYING ILLNESSES THAT HARM LIVERS.
If a patient with hepatitis B dies, that liver can’t be transplanted. “The rules dictate that we can’t use diseased organs,” Tran says. But new breakthroughs in treating underlying diseases also will increase the donor pool. With the recent discovery of a cure for hepatitis C, for example, the number of healthy donated livers is expected to rise. “If we can find a cure for hepatitis B,” she says, “or prevent people from damaging their livers through alcohol and bad dietary choices in the first place, we will both increase the donor pool and reduce the number of people who need a new liver. It’s a win-win. And it’s within reach.”
Tran is medical director of Liver Transplantation at the Cedars-Sinai Liver Disease and Transplant Center. She specializes in liver disease, failure, and transplantation as well as immunotherapy and infectious diseases.
Jaime D. Moriguchi, MD, cardiologist:
PAY IT FORWARD.
Moriguchi suggests a three-pronged approach to solving the donor-shortage dilemma. First, if your loved one was lucky enough to receive a heart, pay it forward. “Ask five members of your family to become donors, then have each convince another five people to do the same,” he says. Second, launch a major outreach program to inspire people to become donors. “I’d like to see news programs air positive stories about transplant patients, and have patients visit schools and offices,” Moriguchi says. “Many people simply are not aware of the need, the shortage, and the good they can do with no risk to themselves.” Third, make organ donation the default setting, as some countries in Europe do. Instead of opting in, everyone would be an organ donor unless they specifically opt out.
Moriguchi is medical director of the Mechanical Circulatory Support Program at the Cedars-Sinai Heart Institute. His areas of expertise include advanced heart failure and transplant cardiology.
Fardad Esmailian, MD, thoracic and cardiac surgeon:
PRESERVE DONATED ORGANS LONGER.
Donated hearts don’t last long outside the body. “We have a window of about three to four hours from the time a donor dies to when the heart must be transplanted into the waiting patient for the best outcome,” Esmailian says. “We need a better method to preserve hearts for a longer period of time so more patients can be helped.”
Biotech firm TransMedics has developed the Organ Care System, a breakthrough technology also known as “heart in a box.” The investigational device could potentially allow clinicians to store a donated heart for up to twice as long as currently possible, dramatically increasing the heart’s viability. Sometimes, brain death triggers temporary dysfunction of the heart, but given a little time, the heart will heal. “If such hearts could be stored properly until the dysfunction reverses,” Esmailian says, “it would increase the pool of hearts that are healthy enough to be transplanted by some 20 percent.” The device, already in commercial use in Europe and Australia, awaits Food and Drug Administration (FDA) approval.
Esmailian is surgical director of Heart Transplantation at the Cedars-Sinai Heart Institute. His areas of expertise include transplant cardiology as well as mitral valve surgery, aortic valve surgery, coronary artery bypass surgery, and ventricular assist devices.
Andrew Klein, MD, transplant surgeon:
MAKE THE SYSTEM FAIR.
The way donated organs are distributed across the U.S. is unfair and must change to better match supply and demand, according to Klein. The system is divided into 11 regions, clustering together states that share a history of closeness and cooperation, such as those in New England. “The trouble is that some of the regions have far more people than others,” Klein says. “Patients are stuck in whatever region they happen to live in.”
Some areas, such as California and New York, also receive a greater number of sick people — including the most challenging cases — because of the abundance of excellent medical facilities. That means more people competing for few organs.
The inequities lessen dramatically if you reconfigure the regions and reduce their number to four. While bureaucratic obstacles have made that difficult, things are moving in the right direction: Soon, there will be eight rather than 11 regions. “That’s good, but it’s not enough,” Klein says. “We need a major push to get this down to four regions and make the system equitable for all Americans.”
Klein is director of the Cedars-Sinai Comprehensive Transplant Center and the Esther and Mark Shulman Chair in Surgery and Transplantation Medicine. His areas of expertise include liver disease, transplantation, and immunobiology. He helped establish rules and guidelines for the nation’s transplant system and is former chair of the United Network of Organ Sharing’s Liver and Intestinal Transplantation Committee.
A Thing of the Past
Sometimes, the ideal solution is the one you don’t need to use in the first place. Many experts hope for a day when the old adage “an ounce of prevention is worth a pound of cure” will truly take hold. Also, even as underlying diseases develop, new treatments and cures could make the need for organ transplantation much less common than it is today.
Eduardo Marbán, MD, PhD, cardiologist and heart researcher:
REVERSE HEART DAMAGE.
Marbán wants to render organ transplantations unnecessary. That means intensifying research on diseases thought to be incurable so patients can be healed without resorting to donated organs. “My lab is investigating the possibility that ‘irreversible’ damage to hearts may, in some cases, be reversible,” Marbán says. “Early-stage clinical trials of cell therapy in heart attack patients have yielded encouraging results. If we can heal the heart instead of removing it, transplants might be avoided.”
To that end, science may have much to learn from the animal kingdom. For example, newts regrow limbs after amputation. “If we can figure out how they do that, we may be able to figure out how to regenerate damaged tissue in humans, too,” Marbán says. “I see organ transplantation as nothing more than an interim technology, tiding us over until we know how to make sick organs healthy or prevent them from decaying in the first place.”
Marbán is director of the Cedars-Sinai Heart Institute and one of the world’s leading cardiologists and heart researchers. His pioneering research, focusing on the molecular and cellular mechanisms involved in heart disease, has translated into key advances in stem cell treatments for heart attack and heart failure.
Danny Ramzy, MD, PhD, thoracic and cardiac surgeon:
BECOME YOUR OWN ORGAN DONOR.
“There is only one way to end the shortage problem while also ending organ rejection and the dangers of immunosuppression,” Ramzy says. “Make each and every person their own organ donor.” Once the purview of science fiction, stem cell technology has brought Ramzy’s dream within reach. Induced pluripotent stem cells (iPSCs) are created from an adult cell, then transformed to mimic embryonic stem cells that can be grown into specific tissues, including skin, lung, liver, or heart. Thanks to iPSCs, the day is nearing when scientists will be able to custom-build new organs to replace those that are failing. “The technology still has far to go,” Ramzy explains, “but we’re getting ever closer to creating organs that are a perfect genetic match for every patient. That’s the holy grail, and I’m hopeful that I will see it during my lifetime.”
Ramzy is director of Robotic and Minimally Invasive Cardiac Surgery and surgical director of Lung Transplantation. He specializes in cardiothoracic surgery.
Clive Svendsen, PhD, stem cell scientist:
GROW PART OF A NEW ORGAN.
It may take some time before a whole organ can be grown out of stem cells. In addition, some organ systems, such as the nervous system, are so complex that transplantation may be impossible. Still, an elegant solution may exist. “We could simply replace only the part of the organ that’s sick,” Svendsen says. His team has successfully injected stem cells into brains and spinal cords and observed the damaged tissue rejuvenate. “The stem cells seem to migrate to the diseased areas,” he explains. “As the technology evolves, we may be able to slow the progression of serious diseases of the nervous system like ALS [amyotrophic lateral sclerosis] and Parkinson’s.” He soon may see his research translate into a viable treatment of the future: The FDA just approved a Phase I clinical trial for ALS.
Svendsen is professor of Medicine and Biomedical Sciences at Cedars-Sinai, director of the Board of Governors Regenerative Medicine Institute, and the Kerry and Simone Vickar Family Foundation Distinguished Chair in Regenerative Medicine. He also heads the Svendsen Laboratory, which focuses on stem cell technology to battle neurodegenerative diseases such as ALS, Huntington’s, Alzheimer’s, and Parkinson’s.
Joyette Jagolino, RN, transplant nurse:
CONFRONT THE OBESITY EPIDEMIC.
“It is my dream that someday transplanting organs no longer will be necessary,” Jagolino says. “That may never happen, but awareness about disease prevention and a healthier lifestyle are steps in the right direction.” According to The State of Obesity: Better Policies for a Healthier America, “if we fail to change the course of the nation’s obesity epidemic, the current generation of young people may be the first in American history to live shorter, less healthy lives than their parents.”
Obesity can lead to diabetes and hypertension, the two most common causes of kidney failure. Overweight patients experience increased risk for heart disease, stroke, and fatty liver disease. If the obesity rate were lower, the incidence of organ failure could be reduced as well.
Jagolino is the service line manager at Cedars-Sinai’s Comprehensive Transplant Center.
The body is hardwired to repel invaders, and when it receives an organ transplant, the immune system goes into overdrive trying to expel it. That’s why transplant patients take immunosuppressant drugs for the rest of their lives. The drugs work well — so well that patients can end up in a Catch-22: If the immune system is successfully weakened, the body stops trying to reject the new organ but becomes vulnerable to serious diseases, including cancer and cardiovascular disease. Immunosuppressant drugs also can trigger side effects such as high blood pressure and kidney failure. The brightest minds in transplantation are working on this challenge.
Donald C. Dafoe, MD, transplant surgeon and scientist:
RESTORE THE PANCREAS.
Most pancreas transplants are performed to treat Type 1 diabetes, an autoimmune disease in which the immune system attacks the pancreas and destroys insulin-producing cells (also known as beta cells). Without insulin, blood sugar levels rise to dangerous levels. “We can transplant the pancreas, but the surgery is reserved mainly for those with kidney failure from diabetes who need a kidney transplant at the same time. The risks of such complex surgery can be serious,” Dafoe says.
Fortunately, he adds, “there may be a better approach.” Using induced pluripotent stem cells, he and his team grew healthy beta cells and injected them into diabetic mice. The result? The transplanted cells started producing insulin. These insulin-producing cells could be generated from a specific patient’s own skin cells, thereby avoiding rejection. If the experimental technology works, “future patients may still need to take immunosuppressant drugs due to recurrent autoimmune attack — but hopefully at far lower doses and with fewer side effects.”
Dafoe is director of Surgical Education in Transplant Surgery, director of the Pancreas Transplant Program in the Comprehensive Transplant Center, and the Eris M. Field Chair in Diabetes Research. His research focuses on islet and pancreas transplantation in the treatment of diabetes mellitus. He also is investigating the growth and development of insulin-producing cells from embryonic stem cells.
Ashley Anh Vo, PharmD, transplant immunotherapy specialist:
REQUIRE INSURANCE COMPANIES TO COVER SENSITIZED PATIENTS.
Some transplant patients need a little extra help. If they’ve been pregnant, had blood transfusions, or had a previous transplantation, their blood has developed antibodies that make it incompatible with most donated organs. Only about 10 percent of such patients can receive a transplant. Treatment with intravenous gamma globulin (IVIG) raises that number to 35 percent and, if IVIG is combined with the drug rituximab, the compatible patients figure rises to 80 percent. IVIG therapy was first adapted for use in transplantation by researchers led by Stanley C. Jordan, MD, director of Nephrology, director of the HLA and Transplant Immunology Laboratory at the Cedars-Sinai Comprehensive Transplant Center, and medical director of the center’s Kidney Transplant Program.
“The problem is that some payers do not cover desensitization treatments, and that should change,” Vo says. One year of dialysis costs around $85,000. By contrast, annual transplant costs after the first year are $19,000. “Paying for desensitization therapies would actually save money.”
Vo is administrative director of the Transplant Immunotherapy Program at the Cedars-Sinai Comprehensive Transplant Center. She previously was a clinical research coordinator for the Cedars-Sinai Center for Kidney and Liver Diseases and Transplantation.
Lawrence S. Czer, MD, cardiologist:
GIVE DOCTORS TIME TO RUN CRUCIAL HEART TESTS.
In an ideal world, every donated heart would be matched perfectly to a waiting patient. The reality is more challenging. “Since a heart is only viable for a few hours after being removed from a donor,” Czer says, “there is not enough time to coordinate the HLA matching, which is based on the HLA blood test in the patient and in the donor.” An HLA test looks for human leukocyte antigen to reveal whether the patient and donor are well-matched.
For kidneys, doctors have approximately 24 hours to coordinate HLA matching between patient and donor. “For the heart, we’re forced to rely only on blood type and body size,” Czer says. The HLA test must be conducted later, when the heart is already in the patient, to determine how much immunosuppressant medication will be needed. Keeping the heart viable longer could potentially allow enough time for HLA matching between each donor and patient.
Czer is medical director of the Heart Transplant Program, associate medical director of the Mechanical Circulatory Support Program, and co-medical director of the Cardiothoracic Surgery Database at Cedars-Sinai. His areas of expertise include transplantation, cardiomyopathy, congestive heart failure, immunotherapy, and myocarditis.
Michael Adams, lung transplant recipient:
MAKE AFTERCARE EASIER ON PATIENTS.
On Dec. 5, 2002, a pastor read Michael Adams his last rites. Adams had been waiting for two new lungs, but hope was fading. Before nightfall, his fortunes changed. He received a call telling him that new lungs were available for him. The surgery at Cedars-Sinai took place the next day.
More than 14 years later, Adams is alive — and deeply grateful. While he has no true complaints, and sings the praises of his surgical team, he hopes one thing will change. “The amount of medication we need can feel overwhelming,” he says of the drugs that stop his body from rejecting the donated lungs. “I will likely have to take 20 different drugs every day for the rest of my life. If they could find a way to condense those drugs into fewer pills, it would ease some of the challenges of living with a transplanted organ.”
Adams lives in San Diego, where he frequently speaks in schools and hospitals on the importance of organ and tissue donation.
Xiaohai Zhang, PhD, immunogenetics expert:
CONVINCE THE BODY TO ACCEPT THE NEW ORGAN.
The body tries to reject a donated organ because it does not recognize it as part of itself. “If we can convince the body that the new organ belongs there, we’ll conquer one of the biggest problems in transplant medicine,” Zhang says. One way is to inhibit expression of certain genes in the recipient. Zhang wants to take the research to the next level, focusing on not only the recipient but also the donor.
“Using a revolutionary gene-editing technique called CRISPR-Cas9, we can do something that was impossible just a few decades ago: We can change the way a gene behaves,” he says. “I believe we can stop donated organs from expressing the genes that throw the recipient’s immune system into overdrive.” He notes that the technology is in its infancy, but it’s shown a lot of promise in animal models. “We’ll get there,” Zhang says.
Zhang, a diplomate of the American Board of Histocompatibility and Immunology, is director of the HLA and Immunogenetics Laboratory at Cedars-Sinai’s Comprehensive Transplant Center.