Improvement of islet function in a bioartificial pancreas by enhanced oxygen supply and growth hormone releasing hormone agonist

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Barbara Ludwig - , Department of Internal Medicine III (Joint first author)
  • Avi Rotem - , Beta-O2 Technologies (Joint first author)
  • Janine Schmid - , Department of Internal Medicine III (Author)
  • Gordon C. Weir - , Harvard University (Author)
  • Clark K. Colton - , Massachusetts Institute of Technology (MIT) (Author)
  • Mathias D. Brendel - , TUD Dresden University of Technology (Author)
  • Tova Neufeld - , Beta-O2 Technologies (Author)
  • Norman L. Block - , University of Miami, Department of Veterans Affairs (Author)
  • Karina Yavriyants - , Beta-O2 Technologies (Author)
  • Anja Steffen - , TUD Dresden University of Technology (Author)
  • Stefan Ludwig - , TUD Dresden University of Technology (Author)
  • Triantafyllos Chavakis - , Institute of Clinical Chemistry and Laboratory Medicine (Author)
  • Andreas Reichel - , TUD Dresden University of Technology (Author)
  • Dimitri Azarov - , Beta-O2 Technologies (Author)
  • Baruch Zimermann - , Beta-O2 Technologies (Author)
  • Shiri Maimon - , Beta-O2 Technologies (Author)
  • Mariya Balyura - , TUD Dresden University of Technology, Beta-O2 Technologies (Author)
  • Tania Rozenshtein - , Beta-O2 Technologies (Author)
  • Noa Shabtay - , Beta-O2 Technologies (Author)
  • Pnina Vardi - , Clalit Health Services (Author)
  • Konstantin Bloch - , Tel Aviv University (Author)
  • Paul De Vos - , University of Groningen (Author)
  • Andrew V. Schally - , University of Miami, Department of Veterans Affairs (Author)
  • Stefan R. Bornstein - , Department of Internal Medicine III (Joint last author)
  • Uriel Barkai - , Beta-O2 Technologies (Joint last author)

Abstract

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 β-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.

Details

Original languageEnglish
Pages (from-to)5022-5027
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America : PNAS
Volume109
Issue number13
Publication statusPublished - 27 Mar 2012
Peer-reviewedYes

External IDs

researchoutputwizard legacy.publication#48974
researchoutputwizard legacy.publication#49337
Scopus 84859475829
PubMed 22393012

Keywords

Sustainable Development Goals

ASJC Scopus subject areas

Keywords

  • Beta cells, Immune isolation, Treatment of diabetes