Volume 10, Issue 1, 2011-2012 - Department of Surgery - University ...

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Cutting-Edge ResearchNew Technology Extends the Life of Donor Organsand Islet Cells for TransplantThe University of Arizona Department of Surgery and other highly specialized transplant centers aroundthe world are furthering the next generation of treatments for organ failure and for type 1 diabetes.New technology pioneered by researchersat the UA Department ofSurgery and small business collaboratorscould profoundly extend the viability oforgans and pancreatic islet cells, expandingthe global reach of transplant centersand allowing for more critically neededtransplants.Islet cell allotransplants involve collectingislets from a donor pancreas andinfusing them into the liver of a personwith life-threatening brittle diabetes mellitus.The cells produce insulin from theliver, often curing the patient’s diabetes.Getting a donated pancreas and itscells to the patient in time is challenging,as the organ and its islet cells candie during transportation. The longer thetransportation process takes, the moretissue dies. Surgeons race against time,especially in cases where the organ musttravel a great distance.Klearchos K. Papas, PhD, and histeam are evaluating a relatively simplemethod of preserving organs throughimproved oxygenation. They have createdthe tools necessary to preserve andtransport not only pancreata that are tobe used to isolate and purify islet cells,but also other organs.Klearchos K. Papas, PhD, developed technology toallow donor organs and islet cells to be transportedlonger distances.“For example, this technology couldextend the life of hearts, increasing thenumber of viable organs available fortransplant,’’ said Dr. Papas, professor ofsurgery in the Division of AbdominalTransplantation and scientific directorof the Institute for Cellular Transplantation.Dr. Papas believes the technologycan extend the life of a donated heart to12 hours or more, as opposed to the fourto six hours currently acceptable, allowingfor better matches, access to morepatients, and reduced cost.Dr. Papas and his team have advancedthe technology through fundingby the National Institutes of Health(NIH) Small Business InnovationResearch Program. Dr. Papas, an engineer,came to the UA in 2011 from theUniversity of Minnesota. He and his teamconducted early proof-of-conceptresearch through seed funding from privatedonations from the Iacocca FamilyFoundation, the Carol Olson MemorialResearch Fund and the Schott Foundation.That research led to NIH funding.Oxygen is the key in extending thelife of an organ, and scientists have useda variety of methods in an attempt to sufficientlyoxygenate tissues. “Traditionally,a pancreas or other organ is placed inwhat is effectively an ice bucket, obviouslynot an ideal method of transportingan organ,’’ Dr. Papas said.Dr. Papas tapped intoexisting technology used in theSea Wolf nuclear submarine to designa portable device that can createoxygen from a small amount of waterin order to pump humidified oxygenenrichedgas through the organ’svessels during transportation, atechnique known as persufflation.The use of persufflation in preservingorgans had been limited in the pastbecause a simple method for using itduring transportation – especially by air– was lacking. The new, portable technology,which eliminates the need for gascylinders, is ready for clinical translationand will be tested in pilot human trials inEurope in 2012, Dr. Papas said.The technology and tools developedby Dr. Papas and his team also couldaid in extending the life of organs fromdonors after cardiac death.“For instance, the vast majority ofhearts from donors after cardiac death arenot used for transplant because currentprotocols are not able to properly preservetheir viability,” said Dr. Papas.“The longer you wait, the more theorgan dies.’’Dr. Papas and his team, through agrant from the Diabetes Research WellnessFoundation, are working with theUniversity of Newcastle and King’s8
Athens-Geneva-Tucson ProjectKlearchos K. Papas, PhD, and his team are joining in an internationaleffort to expand islet transplants to patients in Europe with brittle diabetesmellitus.In what is known as the Athens-Geneva-Tucson Project, the UA is sendingtheir new tools, technologies, and staff to aid in an effort to bring islet transplantationto Athens.Theodore Karatzas, MD, a surgeon from Athens, hoped to provide islettransplants to his critically ill diabetic patients in Greece. However, Greece doesnot have an islet cell transplant center, which would cost millions of dollars tobuild and operate.Geneva has a very active and highly successful islet transplant program.Dr. Karatzas entered into an agreement with Dr. Thierry Berney, MD, whodirects the program at the University of Geneva, that when a donated pancreasbecomes available in Greece, it would be flown to Geneva, where the islet cellswould be isolated and flown back to Athens for transplantation.Twice an attempt was made, but twice the islet cells were of insufficientnumbers and quality after isolation in Geneva for a successful transplant, presumablybecause it took too long to get the pancreas to Geneva.Drs. Papas, Karatzas, and Berneyhave teamed up and are expected to usethe new technologies and tools to makeislet transplantation a reality in Athens.Technologies developed by Dr. Papasand his team, thanks to funds fromthe National Institutes of Health andJuvenile Diabetes Research Foundation,can better preserve the pancreas, transferislets more safely, and determine ifthe cells are viable before transplantation.A highly trained UA team is aidingin the project. Bill Scott, who is gettinghis PhD in biomedical engineering, willbe in Athens; he will board an airplanewith the equipment and the organ andCollege in London to determine whetherpersufflation can extend the viabilityof pancreata from donors after cardiacdeath. They also are examining whetherit could expand the viability of organs indonors over age 50.“The early data is very promising,’’Dr. Papas said.UA researchers test the persufflation device inthe U.S. in preparation for the Athens-Genevaproject.fly to Geneva. Kate Mueller, a UA research specialist, will be stationed in Genevaand will evaluate the islets. She will place them in specialized culture containersand fly with them back to Athens, where she will reevaluate them to determineif they remain viable for transplantation.The new technologies developed by Dr. Papas and his team are improvingeach step in the process, with the hope of successful long-distance transplantation.The goal is to create centers that can provide transplants using organsfrom thousands of miles away, expanding the number of successful proceduresthroughout the world.“The successfuldevelopment ofthis technologywill help savelives by increasingthe numberof patientsreceiving transplants.”– Horacio Rilo, MDIslet Transplants at UAIslet autotransplants (self-donated)currently are performed at The Universityof Arizona Medical Center to treatchronic pancreatitis. The UA Departmentof Surgery Comprehensive Center forChronic Pancreatitis, in conjunctionwith the Institute for Cellular Transplantation,under the direction of HoracioRilo, MD, has performed 30 isletautotransplants to date. The UA hopesto begin islet allotransplants for patientssuffering with type 1 diabetes mellitusin 2012.Islet transplants to treat patientswith type 1 diabetes mellitus are currentlyin Phase 3 clinical trials in the U.S.,sponsored by the National Institutesof Health.“The number of patients needingand waiting for a lifesaving transplantfar outpaces the supply of availableorgans,” said Dr. Rilo. “The successfuldevelopment of this technology will helpsave lives by increasing the number ofpatients receiving transplants.”Rainer W.G. Gruessner, MD, chiefof the Division of Abdominal Transplantationand chairman, UA Departmentof Surgery, added, “Both islet allotransplantsand pancreas transplants havebeen shown to be successful options forpatients with diabetes mellitus and itsadvanced secondary complications,such as metabolic control problems,end-stage renal disease, neuropathy,and gastropathy.“While results for pancreas transplantshave beensteadily improvingover the pastfour decades, withone-year patientsurvival rates ofmore than 95 percentand one-yeargraft survival ratesof more than 80percent, the resultsof islet transplantscontinue to trailthose of pancreastransplants,” Dr. Gruessner said.“Emphasizing islet allotransplants asa research focus within the UA Departmentof Surgery will establish the departmentas a national and internationalleader in transplant options for patientswith insulin-dependent diabetesmellitus.”9
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