Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 109, Issue 13, Pages 5022-5027Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1201868109
Keywords
treatment of diabetes; immune isolation; beta cells
Categories
Funding
- Deutsche Forschungsgemeinschaft [SFB 655, KFO 252, BR 1179]
- Dresden Tumor Centre of Excellence, Center for Regenerative Therapies Dresden (CRTD)
- Paul Langerhans Institute Dresden
- German Center for Diabetes Research (DZD)
- Medical Research Service of the Veterans Affairs Department
- University of Miami Miller School of Medicine
- Division of Hematology/Oncology
- Department of Pathology
- Department of Medicine
- Austin Weeks Family Endowment for Urologic Research
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Islet transplantation is a feasible therapeutic alternative for metabolically labile patients with type 1 diabetes. The primary therapeutic target is stable glycemic control and prevention of complications associated with diabetes by reconstitution of endogenous insulin secretion. However, critical shortage of donor organs, gradual loss in graft function over time, and chronic need for immunosuppression limit the indication for islet transplantation to a small group of patients. Here we present a promising approach to address these limitations by utilization of a macrochamber specially engineered for islet transplantation. The s.c. implantable device allows for controlled and adequate oxygen supply and provides immunological protection of donor islets against the host immune system. The minimally invasive implantable chamber normalized blood glucose in streptozotocin-induced diabetic rodents for up to 3 mo. Sufficient graft function depended on oxygen supply. Pretreatment with the growth hormone-releasing hormone (GHRH) agonist, JI-36, significantly enhanced graft function by improving glucose tolerance and increasing beta-cell insulin reserve in rats thereby allowing for a reduction of the islet mass required for metabolic control. As a result of hypervascularization of the tissue surrounding the device, no relevant delay in insulin response to glucose changes has been observed. Consequently, this system opens up a fundamental strategy for therapy of diabetes and may provide a promising avenue for future approaches to xenotransplantation.
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