Abstract: SA-PO530
Allogeneic "Neo-Islets" Composed of Adipose-Derived Stem and Islet Cells Durably Reduce Diabetic Pet Dogs' Insulin Needs Without Requiring Immunosuppression (INAD 012-776)
Session Information
- Diabetic Kidney Disease: Basic - III
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 601 Diabetic Kidney Disease: Basic
Authors
- Gooch, Anna, SymbioCellTech, Salt Lake City, Utah, United States
- Westenfelder, Christof, University of Utah School of Medicine, Salt Lake City, Utah, United States
Background
We demonstrated that allogeneic, ip administered “Neo-Islets” (NIs), aggregates of cultured islet cells (ICs) and immune- and cyto-protective Adipose Derived Stem Cells (ASCs), 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). Comparable euglycemia was achieved with dog- or human-derived NIs in STZ-diabetic NOD/SCID mice. Here we update our report on an FDA supervised study using NI therapy in diabetic pet dogs.
Methods
Insulin dependent, diabetic pet dogs were included; 8 enrolled; 6 treated; and 4 followed for ≥ 6 mos. Pre-treatment serum samples were tested for islet autoantibodies. Comorbidities and blood glucose levels were treated. Allogeneic NIs were given once ip (2.5x10e5/kg bw). No encapsulation or antirejection agents were used. Blood glucose levels, insulin need and antibody responses were monitored.
Results
Prior to treatment 3 dogs had islet autoantibodies indicating autoimmunity. NIs appear to engraft, redifferentiate and physiologically produce insulin, and are neither rejected by auto- or allo-immune attacks, as evidenced by (i) an absent IgG response to the administered NIs, and (ii) progressively, durably (≥ 12 mos) and improved glycemic control, achieved with an up to 50% reduction in daily insulin need paralleled by a fall in serum glucose (See Figure). No adverse events attributable to therapy have been observed to date. While no dog has achieved insulin independence, preclinical results using human NIs indicate that redosing could accomplish this.
Conclusion
Allogeneic NI therapy is feasible, safe, and durably effective. We conclude that this therapy has significant translational relevance for dog and human T1DM.
(A) Serum glucose levels and (B) insulin need over time. (C) Percent reduction and statistical significance in reductions for each dog.
Funding
- Commercial Support – SymbioCellTech, LLC