Pig cell transplant has one child off insulin; use of embryonic stem cells discussed
MIAMI, Aug. 2002 � More diabetic patients are coming off insulin following pancreatic islet cell transplantation than ever before, according to multiple studies presented at the XIX International Congress of The Transplantation Society held through Aug. 30 at the Westin Diplomat Resort and Spa in Hollywood, Fla. One report of new international data shows 80 percent of patients are remaining insulin free one year after receiving infusions of the insulin-producing cells, a success rate that is on a par with whole pancreas transplantation and markedly improved over the 14 percent rate reported for 1998-2000.
One-year, insulin-free status also was achieved in a child who received a mixture of pig cells, without the use of immunosuppressive drugs and without her immune system attacking the animal cells, reported Dr. Rafael Valdes from the Children's Hospital of Mexico and colleagues from the University of Western Ontario and Diatranz, Ltd., of New Zealand. A second child of the 12 in the study was off insulin for six months and currently requires 75 percent less insulin than before the transplant.
The mixture of cells consisted of islet cells and testicular Sertoli cells taken from neonatal pigs. Sertoli cells are thought to have a special ability to subdue immune system T cells, which normally fight against the presence of anything foreign. The researchers gave the cells to 12 children with type 1 diabetes between the ages of 11 and 17 and did not administer any immunosuppressive drugs to protect the cells from being rejected. Six of the 12 patients have functioning grafts, and subsequent to receiving additional transplanted islets at 20 weeks, they have demonstrated improvements in their islet function.
According to the researchers, the pig cells did not elicit the expected immune system response in the patients, and retransplantation of islets failed to stimulate a secondary response against the pig cells as well.
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"Whether these results can be duplicated by another center remains to be seen," said Dr. Camillo Ricordi of the Diabetes Research Institute at the University of Miami and co-chair of the congress. "The scientific community at large may be skeptical until more data is available and more patients are studied," he added.
Still, the findings suggest it is possible to obtain precious insulin-producing cells from sources other than human pancreases, which like other donor organs, are in scarce supply. Besides there being too few organs, also affecting the availability of islets is the amount of time pancreases can be safely preserved and competition from centers that transplant the entire pancreas. But unlike solid organ transplantation, for every patient needing an islet cell transplant, two donor organs generally are required because one organ alone usually cannot provide a sufficient number of cells for successful engraftment in the patient. Preliminary results from the University of Minnesota suggest that in selected recipients it is possible to achieve consistent insulin independence following transplants of islets from single donors.
With between 120 and 140 million people worldwide suffering from diabetes, much research is focused on making more efficient use of available organs as well as identifying additional sources of viable cells for transplantation.
Embryonic stem cells, which are primitive cells that have the potential to become a wide variety of specialized cell types and are capable of self-renewal, represent a possible answer to this shortage of cells for transplantation because of their ability to proliferate. Stem cells also can be genetically modified, and have proven to be useful in different animal models, as in a study presented by Dr. Bernat Soria of Miguel Hernandez University in Alicante, Spain. Mouse embryonic stem cells were successfully coaxed into producing islets that effectively normalized blood glucose levels within one week of being transplanted into mice with induced diabetes. In other studies presented today, researchers from the University of Alberta, who in 1999 announced success transplanting human islets using a novel immunosuppressive regimen widely known as the "Edmonton Protocol," reported 70 percent of their patients are insulin free at two years and one patient has been off insulin for more than three years. More than 10 centers have seen similar success using some variation of the Edmonton Protocol, the Canadian researchers said.
According to the International Islet Transplant Registry, new data indicates 28 of 35 patients (80 percent) who received islet transplants alone (neither with nor following a kidney transplant) were off insulin at one year. Data from earlier eras found insulin independence achieved in 11 percent of those who received islets with or following kidney transplants between 1990 and 1997, and in 14 percent of patients transplanted between 1998 and 2000.
While preliminary, this newfound success has been due not only to newer methods that seem to do a better job protecting the islets from rejection, but from developments that are making it feasible to culture viable cells from so-called "marginal" organs. By adding the compound perflurocarbon to the standard organ preservation solution, University of Miami researchers, led by Dr. Ricordi, were able to use pancreases from older donors deemed unacceptable for transplantation. The islet cells isolated from these organs were successfully transplanted into patients, many of whom continue to be insulin free.
In nine other cases, Dr. Ricordi's team bathed the islets in a special fluid for up to two days before transplanting them. Initially, all patients were able to get off insulin, he reported. Difficulties arose about one year later for one patient and six months after transplantation for another and the two restarted injections, but at 19 percent of their pre-transplant dose. The remaining seven patients continue to be insulin free, three for nearly one year. Dr. Ricordi's team is the first to show that fragile islets can be safely transported to distant centers that lack their own specialized islet cell isolation facility. Moreover, surgeons at these centers have then been able to transplant their patients with the shipped islets and consistently achieve insulin independence.
Ten years ago, reported cases of patients being completely off insulin following islet cell transplantation were few and far between. But according to a study by the San Raffaele Scientific Institute in Milan, patients transplanted in this era with still functioning grafts have fewer diabetic complications than other diabetic transplant patients. The study of patients who received combined islet and kidney transplants found patients with functioning islets are living longer, are less likely to suffer cardiovascular death and have a lower incidence of atherosclerosis and kidney problems than those patients who received successful kidney transplants but whose islet transplants failed.
The researchers believe these advantages conferred in patients with functioning islets may be due to the islets themselves. These patients require fewer insulin injections and have reduced resistance to insulin.
Held every two years, the International Congress of The Transplantation Society is recognized as the field's most important international scientific meeting. More than 1,600 abstracts covering basic and clinical science are being presented, and nearly 3,000 surgeons, physicians and researchers from 71 countries are in attendance. Co-chairs of the congress are Dr. Ricordi and Dr. Domingo Casadei of the Instituto de Nefrologia in Buenos Aires.
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Source: Transplantation Society
