Correction of diabetic nod mice with insulinomas implanted within Baxter immunoisolation devices

T. Loudovaris, S. Jacobs, S. Young, D. Maryanov, J. Brauker, R. C. Johnson

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

Insulin replacement by injection is clearly not a cure for Insulin Dependent Diabetes Mellitus (IDDM). Replacement of the destroyed islets by pancreas or islet allograft transplantation can achieve the good metabolic control required to prevent diabetic complications, but tissue supply is limited. The problem of islet supply to treat the I million IDDM patients in the USA could be overcome by using immortalized islet β-cells as a donor source. However, before either allogeneic or xenogeneic immortalized β- cells are used, some major problems have to be overcome: control of immortalized cell growth, allograft or xenograft rejection and recurrence of autoimmunity. To tackle these problems we have used a cell impermeable immunoisolation device containing mouse insulinoma cells. Transplantation of devices with insulinomas from NOD mice carrying the Rat-insulin promoter regulated SV40 T-Antigen transgene (RIP-TAg), normalized the blood glucose levels of diabetic NOD mice. Insulinomas from allogeneic CBA/NOD-RIP-TAg mice were also capable of normalizing diabetic NOD mice. Not only were non- fasting blood glucoses normalized but when given an intraperitoneal injection of glucose, the corrected mice had a near normal clearance of glucose from the blood. When the devices were removed from normalized mice they became diabetic again, demonstrating that the immunoisolation device was capable of protecting against both alloimmune and autoimmune destruction. The results with allogeneic mouse β-cells suggest the possibility that immortalized human β-cells could be an effective source of tissue to correct diabetes in IDDM patients without the use of immunosuppression.

Original languageEnglish (US)
Pages (from-to)219-222
Number of pages4
JournalJournal of Molecular Medicine
Volume77
Issue number1
DOIs
StatePublished - 1999
Externally publishedYes

Keywords

  • Allografts
  • Diabetes
  • Immunoisolation
  • Insulinoma
  • Islet cells

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery
  • Genetics(clinical)

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