Bio-artificial pancreas providing immune protection for

pig islet transplantation

Barbara Ludwig1,2

1Department of Medicine, University Hospital Carl Gustav Carus, TechnischeUniversit�t Dresden, Dresden, Germany, 2Paul Langerhans Institute Dresden,Dresden, Germany

Islet transplantation as a biological b-cell replace-ment therapy has emerged as a promising optionfor achieving restoration of metabolic control intype 1 diabetes patients. In the Dresden Centre thistherapeutic option has been successfully integratedin clinical diabetes care. However, a number offactors hamper more widespread utilization of thistherapeutic modality. One big limitation toadvancement in islet transplantation is access tohigh-quality donor pancreas. Secondly, partial ortotal loss of the islet graft still occurs within a fewweeks after implantation in a large number ofcases. The high rate of early transplant dysfunctionhas been attributed to poorly viable and/or func-tional islets and is mediated by innate inflamma-tory response at the intravascular (hepatic)transplant site and critical lack of oxygen supplyprior to islet engraftment. In addition, the diabe-togenic effect of inevitable immunosuppressiveagents, limited control of alloimmunity, and therecurrence of autoimmunity limit the long-termsuccess of islet transplantation.Islets of Langerhans from animal donors pro-

vide an attractive alternative to human islets forthe treatment of diabetes. They have the potentialto overcome many of the for-mentioned hurdlesand therefore allow for wider utilization of thistherapeutic modality. Xenografts feature readyavailability and cross-species therapeutic potential.

The exploration of isolated islets from geneticallydefined/modified xenografts, their comprehensivefunctional analysis and in vivo study in pre-clinicaldiabetic models will facilitate the vision of porcineislet transplantation to be the first example ofsuccessful xenotransplantation.The recently established porcine islet program in

Dresden focuses on the development of strategiesthat address key issues in current clinical islettransplantation: (i) Pig source for clinical islettransplantation can resolve the problem of limitednumber and quality of donor organs; (ii) Estab-lishment of an extravascular (subcutaneous) trans-plant site that is specifically designed to maintainphysiological oxygen supply; (iii) Application ofthe macrochamber provides a sufficient barrierbetween the donor islet graft and recipient organ-ism to abrogate inflammatory and immunologicalreactions.In comprehensive pilot trials, we could demon-

strate that utilization of the bioartificial pancreasallows for long-term restoration of normoglycemiain diabetic rodent and large animal (minipig)allogeneic transplant models without applicationof immunosuppressive drugs. This approach mayset the basis for a feasible and safe concept ofxenogeneic islet transplantation in man and there-fore lead to a substantial progress in the field ofislet xenotransplantation.

Reference1. Ludwig B, Zimerman B, Steffen A et al. A Novel

Device for Islet Transplantation Providing ImmuneProtection and Oxygen Supply. Horm Metab Res 2010; 42:918–922.

Berlin Symposium Xenotransplantation 2011 – Abstracts

Xenotransplantation 2012: 19: 2–22Printed in Singapore. All rights reserveddoi: 10.1111/j.1399-3089.2011.00680.x

� 2012 John Wiley & Sons A/S

XENOTRANSPLANTATION

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