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Kidney Week

Abstract: SA-PO529

Redosing of Dysglycemic, Diabetic Mice with Neo-Islets, Aggregates of Adipose Stem Cells and Pancreatic Islet Cells, Achieves Euglycemia: Relevance to the Therapy of Diabetic Dogs

Session Information

Category: Diabetic Kidney Disease

  • 601 Diabetic Kidney Disease: Basic

Authors

  • Westenfelder, Christof, University of Utah School of Medicine, Salt Lake City, Utah, United States
  • Gooch, Anna, SymbioCellTech, Salt Lake City, Utah, United States
Background

We demonstrated that allogeneic, ip administered “Neo-Islets” (NIs), aggregates of cultured islet cells and immune- and cyto-protective Adipose Derived Stem Cells, reestablished durable normoglycemia through omental engraftment and splenic and omental upregulation of Tregs, in autoimmune T1DM NOD mice without immunosuppressive agents (SCTM 2017;6:1631). Similarly, our FDA pilot study in insulin dependent pet dogs (INAD 012-0776) demonstrates that allogeneic NI therapy (i) is effective in significantly improving both glycemic control and the need for insulin (> 1 year); and (ii) does so without eliciting an allo-immune response (see abstract this session). Because the need for insulin is not eliminated in dogs, the current study was conducted to test whether redosing, independent of modulating an allo-immune response, is effective in further reducing the need for insulin. Redosing was therefore tested using Streptozoticin-diabetic (STZ) NOD/SCID mice.

Methods

Blood glucose levels were initially controlled with insulin pellets (Linbits) in 12 STZ-diabetic mice prior to i.p. NI or vehicle treatment (2x10e5 NIs/kg bw) (n=6 per group). Mice were followed (blood glucose; weight, ip Glucose Tolerance Test [GTT]) for ~8 weeks.

Results

No mice in the treated group died vs. 4 controls. NI therapy significantly improved glycemic control without achieving euglycemia vs controls x50 days. Therefore, on day 60, mice were redosed and followed as detailed above. This second dose of normalized both blood glucose levels and GTTs.

Conclusion

We conclude that these data support the planned redosing of dogs whose need for insulin has been reduced but not eliminated through allogeneic NI treatment, as initial allogeneic treatment of these dogs failed to elicit an immune response. We expect that doing so may lead to insulin independence, i.e., in analogy to islet transplant recipients who require several doses of islets but who are, however, treated with anti-rejection drugs.

Funding

  • Commercial Support