Abstract: TH-PO888
Allogeneic “Neo-Islets,” Composed of Mesenchymal Stem and Islet Cells, Are Immune Protected and Control, After i.p. Administration, Auto-Immune Type 1 Diabetes Mellitus in Pet Dogs
Session Information
- Diabetic Kidney Disease: Basic - I
October 25, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 601 Diabetic Kidney Disease: Basic
Authors
- Westenfelder, Christof, SymbioCellTech, SLC, Utah, United States
- Gooch, Anna, SymbioCellTech, SLC, Utah, United States
- Hu, Zhuma, SymbioCellTech, SLC, Utah, United States
- Zhang, Ping, SymbioCellTech, SLC, Utah, United States
Background
Curative T1DM therapies are needed that do not depend on potentially toxic anti-rejection drugs, encapsulation devices or the requirement for up to 5 pancreas donors per islet transplant. 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. Comparable euglycemia was achieved with dog-derived NIs in STZ-diabetic NOD/SCID mice (SCTM 2017;6:1631). Here we report on an FDA supervised pilot study (INAD 012-776) using this NI therapy in 2 insulin-dependent pet dogs.
Methods
Insulin dependent (≥ 6 months), diabetic pet dogs, ≤12 kg, were included, 6 enrolled; 3 treated, and 2 (Dogs 1 and 2, male) followed for 6 months. Pre-treatment serum from Dog 1 and Dog 2 was tested for the presence of islet autoantibodies, and comorbidities and blood glucose levels were treated. 2x10e5 allogeneic NIs per kg b.wt. were then given i.p. Blood glucose levels, insulin requirements and formation of antibodies to allogeneic NIs were closely monitored.
Results
Prior to treatment Dog 1 had no islet autoantibodies, suggesting insulin resistance, while Dog 2 had islet autoantibodies, indicating autoimmunity. Both dogs have improved glycemic control. Dog 2’s insulin requirements have decreased by 50% after 6 months. Neither dog developed antibodies to the administered NIs, and no adverse events related to treatment were observed.
Conclusion
This ongoing pilot study in diabetic dogs demonstrates that NI therapy progressively reduces insulin requirements. This was achieved, without anti-rejection drugs. NIs, as engineered here, provide a novel therapy that, we posit, has significant translational relevance to clinical T1DM.
We thank site PIs Drs. Rance Sellon, WSU, Pullman, WA, Natasha Loy Son and Julie Fisher, Veterinary Specialty Hospital, San Diego, CA, for their excellent collaboration.
Funding
- Commercial Support – SCT