262-OR: INAD 012-776 Pilot Study: Allogeneic 'Neo-Islets,' Composed of Mesenchymal Stem and Islet Cells, Are Immune Protected and Dose-Dependently and Durably Control Autoimmune T1DM in Pet Dogs
| Autor: | Anna Gooch, Sabiha S. Chowdhury, Christof Westenfelder |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
medicine.medical_specialty
geography geography.geographical_feature_category business.industry Endocrinology Diabetes and Metabolism Insulin medicine.medical_treatment Autoantibody Nod Islet medicine.disease Endocrinology Immune system Insulin resistance Downregulation and upregulation Internal medicine Internal Medicine medicine business NOD mice |
| Zdroj: | Diabetes. 68 |
| ISSN: | 1939-327X 0012-1797 |
| DOI: | 10.2337/db19-262-or |
| Popis: | 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. Insulin dependent, diabetic pet dogs, ≤12 kg, were included; 7 enrolled; 5 treated; and 4 followed for ≥6 mos. Pre-treatment serum samples were tested for islet autoantibodies. Comorbidities and blood glucose levels were treated. NIs were given once ip in a dose escalation protocol (2.5x10e5 to 5x10e5/kg bw). Blood glucose levels, insulin need and antibody responses were monitored. Prior to treatment 3 dogs had islet autoantibodies indicating autoimmunity, and 1 dog had no islet autoantibodies, potentially indicating insulin resistance. NIs appear to engraft, redifferentiate and physiologically produce insulin, and are neither rejected by auto- or allo-immune attacks, as evidenced by (a) an absent IgG response to the administered NIs, and (b) progressively, durably (≥ 12 mos) and dose-dependently improved glycemic control, achieved with a 50% reduction in daily insulin need paralleled by a fall in HbA1c in one dog from 12.1 to 6.8%. One dog was not compliant with keeping blood glucose levels controlled in the first few weeks post treatment and failed to respond. We conclude that this novel therapy may have significant translational relevance to human T1DM. We thank site PIs Drs. R. Sellon, WSU, Pullman, WA, N. Loy Son and J. Fisher, Veterinary Specialty Hospital, San Diego, CA, for their excellent collaboration. Disclosure C. Westenfelder: Consultant; Self; SymbioCellTech. S.S. Chowdhury: Employee; Self; SymbioCellTech. A. Gooch: Board Member; Self; SymbioCellTech. |
| Databáze: | OpenAIRE |
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