Transplantation of human islets without immunosuppression

Transplantation of pancreatic islets is emerging as a successful treatment for type-1 diabetes. Its current stringent restriction to patients with critical metabolic lability is justified by the long-term need for immunosuppression and a persistent shortage of donor organs. We developed an oxygenate...

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Published inProceedings of the National Academy of Sciences - PNAS Vol. 110; no. 47; pp. 19054 - 19058
Main Authors Ludwig, Barbara, Reichel, Andreas, Steffen, Anja, Zimerman, Baruch, Schally, Andrew V., Block, Norman L., Colton, Clark K., Ludwig, Stefan, Kersting, Stephan, Bonifacio, Ezio, Solimena, Michele, Gendler, Zohar, Rotem, Avi, Barkai, Uriel, Bornstein, Stefan R.
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences 19.11.2013
NATIONAL ACADEMY OF SCIENCES
National Acad Sciences
Subjects
Antibodies
Bioartificial Organs
Biological Sciences
Blood & organ donations
C-Peptide - metabolism
Diabetes
Diabetes Mellitus, Type 1 - therapy
Diffusion Chambers, Culture
Glucose Tolerance Test
Humans
Immunohistochemistry
Immunosuppression - methods
Insulin
Islets of Langerhans
Islets of Langerhans transplantation
Islets of Langerhans Transplantation - immunology
Islets of Langerhans Transplantation - methods
Male
Medical treatment
Middle Aged
Oxygen
T lymphocytes
Tissue grafting
Transplantation
Transplants & implants
Treatment Outcome
Type 1 diabetes mellitus
β-cell replacement
immune barrier
oxygenation
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Summary:Transplantation of pancreatic islets is emerging as a successful treatment for type-1 diabetes. Its current stringent restriction to patients with critical metabolic lability is justified by the long-term need for immunosuppression and a persistent shortage of donor organs. We developed an oxygenated chamber system composed of immune-isolating alginate and polymembrane covers that allows for survival and function of islets without immunosuppression. A patient with type-1 diabetes received a transplanted chamber and was followed for 10 mo. Persistent graft function in this chamber system was demonstrated, with regulated insulin secretion and preservation of islet morphology and function without any immunosuppressive therapy. This approach may allow for future widespread application of cell-based therapies.
Bibliography:http://dx.doi.org/10.1073/pnas.1317561110
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Author contributions: B.L., A. Reichel, A.S., B.Z., C.K.C., S.L., S.K., E.B., M.S., Z.G., A. Rotem, U.B., and S.R.B. designed research; B.L., A. Reichel, A.S., B.Z., C.K.C., S.L., S.K., E.B., M.S., A. Rotem, U.B., and S.R.B. performed research; B.L., A. Reichel, A.S., B.Z., A.V.S., N.L.B., E.B., M.S., Z.G., A. Rotem, U.B., and S.R.B. analyzed data; and B.L., A. Reichel, A.S., B.Z., A.V.S., N.L.B., E.B., M.S., Z.G., A. Rotem, U.B., and S.R.B. wrote the paper.
1B.L. and A. Reichel contributed equally to this work.
Contributed by Andrew V. Schally, September 20, 2013 (sent for review August 15, 2013)
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1317561110