204-LB: The In Vitro Characteristics of Human Islet Cells from Diverse Donors, Coaggregated with Human Mesenchymal Stromal Cells to form 'Neo-islets', Are Consistently Identical: Relevance to Clinical Trials in Diabetic Subjects
| Autor: | Christof Westenfelder, Zhuma Hu, Ping Zhang, Sabiha S. Chowdhury, Anna Gooch |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
endocrine system
education.field_of_study geography medicine.medical_specialty geography.geographical_feature_category business.industry Endocrinology Diabetes and Metabolism Insulin medicine.medical_treatment Population Mesenchymal stem cell Enteroendocrine cell Islet Immune system Endocrinology Internal medicine Internal Medicine Medicine business education NOD mice Hormone |
| Zdroj: | Diabetes. 69 |
| ISSN: | 1939-327X 0012-1797 |
| DOI: | 10.2337/db20-204-lb |
| Popis: | We reported that allogeneic “Neo-Islets” (NIs), organoids composed of ~ equal numbers of Mesenchymal Stromal Cells and culture expanded Islet Cells (ICs) do, when given i.p., omentally engraft and permanently restore euglycemia in auto-immune diabetic NOD mice, i.e., without the use of either encapsulation devices or antirejection drugs. Similarly, spontaneously diabetic pet dogs treated with allogeneic canine NIs (cNIs) significantly improve glycemia with ~ 50% reduction in insulin needs (> 2 years), and this without immune response. In preparation for a Phase I Clinical Trial we tested whether human ICs in NIs (hNIs) are biologically comparable to canine Islet Cells (cICs) and cNIs, i.e., cells from a larger diabetes model. In our preclinical mouse and dog studies, insulin and other islet hormone gene expression levels were used as indicators of ICs in NIs to adequately re-differentiate into insulin and islet-specific endocrine cells when implanted i.p., thereby resulting in physiological control of T1DM.Human islet cells from 6 donors of different demographics were cultured, passaged to P4, and their growth rates, insulin and other islet-associated endocrine genes’ expression levels, secretion of insulin in response to glucose stimulation (GSIS), and NI formation abilities were compared. Results: (1) hICs and hNIs show comparable gene expression profiles to those of cICs and cNIs, and hNIs show identical GSIS responses to those of cNIs. (2) Insulin gene expression profiles of hICs are stable as a function of population doublings and independent of donor diversity. In conclusion, these data indicate that donor variability does not appear to be a significant factor in this NI technology, facilitating our IND work and further demonstrating hNIs’ translational potential in a planned Clinical Trial in subjects with T1DM. Disclosure A. Gooch: Employee; Self; SymbioCellTech. S.S. Chowdhury: Employee; Self; SymbioCellTech. P. Zhang: Employee; Self; SymbioCellTech. Z. Hu: Employee; Self; SymbioCellTech. C. Westenfelder: Consultant; Self; SymbioCellTech. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|