Posted 11/1/2007
 By Jaron Terry, APR
Not since the polio vaccine was developed in the 1950s have medical researchers been as enthusiastic about the possible cure of another of the world's most devastating diseases as they are now. OSU Medical Center is one of a select group of medical centers in North America approved to process pancreatic islet cells for human transplant. This clears the way for clinical trials of an innovative treatment that may actually cure type 1 diabetes.
“Last year, fewer than 70 patients in all of North America received pancreatic islet cell transplants,” says Ronald Ferguson, MD, PhD, director of Ohio State University Medical Center's Comprehensive Transplant Center (OSUCTC). “We're pleased that with the new FDA guidelines we can make this innovative treatment available to more diabetic patients. For many of them, it will provide a dramatic new lease on life,” he adds.
The U.S. Food and Drug Administration’s approval of Ohio State’s Investigational New Drug (IND) request to develop and process pancreatic islets that can be injected into humans acknowledges that its facilities meet very rigorous standards for isolating pancreatic islets.
International Attention
“Already, islet cell transplantation is transforming how type 1 diabetes is treated,” says Kwame Osei, MD, FACE, FACP, director, Division of Endocrinology, Diabetes and Metabolism, and Professor of Medicine and Exercise Physiology in Ohio State's Department of Internal Medicine.
 Columbus will be the host city for the 2007 Global Diabetes Summit, with Dr. Osei serving as host on behalf of Ohio State's Diabetes Research Center and the International Diabetes Federation.
“The Global Diabetes Summit is designed to bring together the best minds in the world to consider how we can better manage diabetes. More importantly, we will be discussing strategies like islet transplant that will one day prevent the devastating consequences of this disease,” says Dr. Osei.
For more information on the summit, which will be held November 30 and December 1, 2007,
at the Hilton Columbus Easton, in Columbus, Ohio, click here. | Dr. Ferguson, a nationally respected transplant surgeon, says this addition to the OSUCTC’s capabilities is an excellent example of how collaboration among disciplines leads to new advancements. “For the past four years, Dr. Rajab has been working closely with people from Internal Medicine, the James Cancer Hospital, the Comprehensive Cancer Center (OSUCCC) and other experts within the Medical Center to develop this service. Together, they redesigned existing facilities and work teams to efficiently and cost-effectively create the Islet Transplant Program,” he adds.
Elizabeth Seely, an administrator at Ohio State’s Medical Center who helped create the new program, agrees that collaboration was key. “As we looked at what we needed to establish this program, we realized we already had a great detail of the technology and expertise in the Cell Therapy Laboratory that supports our Bone Marrow Transplant Program,” she says. “It made great economic sense to explore how those resources could be used to support this major new initiative.”
A New Hope
“Our hope is that by transplanting pancreatic islet cells, millions of patients whose pancreases no longer secrete enough insulin to control glucose levels in their blood will be spared the serious complications of diabetes,” says Amer Rajab, MD, PhD, transplant surgeon and director of Ohio State’s Pancreas and Islet Transplant Program.
Dr. Rajab notes that approximately one out of every 10 healthcare dollars spent today goes to the care of patients who are suffering chronic complications of type 1 diabetes. According to a study by the American Diabetes Association, the annual cost of diabetes in medical expenditures and lost productivity rose dramatically from $98 billion in 1997 to $132 billion in 2002. After adjusting for differences in age, gender and race/ethnicity between people with and without diabetes, the study found that those with diabetes incur medical expenses about 2.4 times higher than those without diabetes.
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Ohio State’s Comprehensive Transplant Center
Ohio State University Medical Center performed its first solid-organ transplant, a kidney, in 1967. A little more than two decades later, the first human pancreas was successfully transplanted at Ohio State in 1988. Today, the Medical Center's combined kidney/pancreas transplant program ranks first in Ohio and fourth in the United States. Ohio State's Comprehensive Transplant Center, created in 2005, provides the only comprehensive adult transplant program in central Ohio, and includes – in addition to kidney and pancreas – heart, liver and cellular (blood and marrow) transplants. Last year OSUMC, which has performed nearly 10,000 transplants altogether, became the first academic medical center in Ohio to perform a combined heart-lung transplant. | “More importantly, type 1 diabetes is a devastating disease, with numerous life-threatening complications, including blindness, heart attacks, kidney failure and the loss of limbs,” Dr. Rajab says. “Although solid organ transplant of a whole pancreas is also a cure for diabetes, the magnitude of the operation and the shortage of available, suitable organs continue to be a problem. Whatever we do, there are simply not enough pancreases to meet the need.”
Safety and Potency Assured
Lynn O’Donnell, PhD, director of the Medical Center’s Cell Therapy Laboratory where the pancreatic islets are isolated and processed for transplant, agrees that the shortage of organs is critical. “Often, when a pancreas does become available, it is not in good condition for transplantation as a whole organ. However, the islet cells are still viable,” she says.
Dr. O’Donnell explains that she and Dr. Rajab performed several human islet isolations as part of the FDA review and approval process.
“Each islet treatment is ‘manufactured’ for an individual patient, who is matched according to blood type and other criteria. A pancreas comes into my lab, an enzymatic solution is injected and the organ is reduced to a semi-liquid state in a Ricordi chamber,” she explains. “At this point we can isolate the islet cells from other cells and tissues. Before transplant, we suspend the islets in media and conduct a number of tests to ensure potency and safety.” The entire process takes about eight hours.
Elizabeth Diakoff, MD, an endocrinologist who collaborated with Dr. Rajab and his team to develop the clinical protocols for islet cell transplant, explains that patients who are to receive islet cells are carefully screened before being considered for OSU’s phase I clinical trial.
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| Amer Rajab, MD, PHD, and Lynn O'Donnell, PHD |
“For each patient enrolled in the trial, we must weigh the risks and benefits of this procedure, with the ultimate goal being the prevention of diabetes complications,” says Dr. Diakoff, who also is assistant professor, Division of Endocrinology, Diabetes and Metabolism in OSU’s Department of Internal Medicine. “We know from the Diabetes Control and Complications Trial (a clinical study conducted from 1983 to 1993 by the National Institute of Diabetes and Digestive and Kidney Diseases) that for patients with type 1 diabetes, keeping blood glucose levels as close to normal as possible can slow or prevent complications.
“Patients who stand to benefit the most from this new treatment are those who have had difficulty controlling blood glucose levels with insulin injection,” he says. “In fact, insulin injection will never fully mimic physiologic insulin secretion, and it carries the risk of hypoglycemia, which can also be life-threatening. Islet transplantation, on the other hand, can provide the body with the natural ability to regulate glucose and insulin. That is one of the many advantages of islet transplantation.”
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Hadley Directs OSUCTC Research
Gregg Hadley, PhD, recently joined Ohio State's Comprehensive Transplant Center team as director of Research. His work, which has been widely published in peer-reviewed journals such as Immunobiology of Organ Transplantation, Journal of Experimental Medicine and Journal of Immunology, focuses on the mechanisms of organ allograft rejection and pancreatic islet allograft rejection.
 “My objective is to come up with novel therapeutics to prevent allograft rejection,” Dr. Hadley says. “It's very exciting to join a group as experienced and dedicated as the Ohio State team. As a research scientist, it's gratifying to be part of a team that includes everything from basic research to clinical trials to patient care. Together we can accomplish the 'holy grail' of translating laboratory research directly into bedside care.”
Dr. Hadley came to Ohio State from the University of Maryland Medical School in Baltimore where he most recently served as associate professor of surgery and Microbiology and Immunology. He earned his doctorate in microbiology from the University of Minnesota and completed his postdoctoral fellowship at the University of Michigan. He is a member of several professional organizations, including the American Society of Transplan-tation, and serves on the editorial board of the journal Transplantation.
| Dr. Rajab points out that, in addition to these obvious benefits, islet cell transplantation carries fewer surgical risks than does transplant of a solid organ. “Even if the pancreas supply was greater, the risks of islet cell transplant are far fewer than those of whole pancreas transplant,” he says. The primary method of islet cell transplant is a minimally invasive one-inch incision – similar to that of laparoscopy. The portal vein is then catheterized providing access to the liver, where the pancreatic islet cells are infused over a 30-minute period. “For patients who have scarring from other surgeries, we can access the portal vein through radiologic fluoroscopy, collaborating with interventional radiologistsat OSUMC,” Dr. Rajab adds.
“Many of my patients are extremely excited about this treatment and are eager to be considered for the trial,”
Dr. Rajab says. “All of this is possible because of the high level of collaboration here at Ohio State.
“I’m looking forward to continued collaboration, as well as ongoing research, particularly with Gregg Hadley, who joined the OSUCTC in October (see sidebar story). I’m excited to think that someday we may no longer have to rely on obtaining pancreatic islets because we'll be able to culture an islet cell line in the laboratory,” Dr. Rajab says. “At one point, islet cell transplant was considered science fiction, but, after four years, is now a reality here at Ohio State.”
Translational and Personal
“Islet cell transplantation perfectly embodies our mission, which is to improve people’s lives through innovation in research, education and patient care,” says Fred Sanfilippo, MD, PhD, senior vice president and executive dean for Health Sciences and CEO, OSUMC. Dr. Sanfilippo, who himself is an internationally known transplant scientist and former president of the American Society of Transplantation, says that islet cell transplantation is a great example of translational research. “This innovative therapy had been studied in the laboratory setting for many years before being brought forward to the clinical research stage. OSUMC can help determine if it is indeed the new standard of care for type 1 diabetes.”
“The trick to making this work so well is having really robust interaction among investigators and basic scientists, clinical researchers and clinical practitioners,” says Dr. Sanfilippo. “Without these active connections, it would not have been possible to develop this treatment, which truly represents the personalization of medicine,” he adds.
Personalized health care, the new paradigm in healthcare delivery, focuses on improving patient outcomes by using advances in medicine, such as islet cell transplantation, to deliver the most effective treatments, customized to individual patients.
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from left:
Amer Rajab, MD, PHD, Lynn O'Donnell, PHD, Elizabeth Diakoff, MD, Ronald Ferguson, MD, PHD | |