Insulin expression and C-peptide in type 1 diabetes subjects implanted with stem cell-derived pancreatic endoderm cells in an encapsulation device

• Published in: Cell reports. Medicine Vol. 2; no. 12; p. 100466
• Main Authors: Shapiro, A.M. James, Thompson, David, Donner, Thomas W., Bellin, Melena D., Hsueh, Willa, Pettus, Jeremy, Wilensky, Jon, Daniels, Mark, Wang, Richard M., Brandon, Eugene P., Jaiman, Manasi S., Kroon, Evert J., D’Amour, Kevin A., Foyt, Howard L.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 21.12.2021; Elsevier
• Subjects: Adolescent; Adult; Advanced Basic Science; Aged; C-Peptide - metabolism; Cells, Immobilized - cytology; Diabetes Mellitus, Type 1 - metabolism; Diabetes Mellitus, Type 1 - therapy; Endoderm - cytology; Female; Humans; Insulin - metabolism; Male; Middle Aged; Pancreas - cytology; Stem Cell Transplantation; Stem Cells - cytology; Young Adult
• ISSN: 2666-3791; 2666-3791
• DOI: 10.1016/j.xcrm.2021.100466

These preliminary data from an ongoing first-in-human phase 1/2, open-label study provide proof-of-concept that pluripotent stem cell-derived pancreatic endoderm cells (PEC-01) engrafted in type 1 diabetes patients become islet cells releasing insulin in a physiologically regulated fashion. In this study of 17 subjects aged 22-57 with type 1 diabetes, PEC-01 cells were implanted subcutaneously in VC-02 macroencapsulation devices, allowing for direct vascularization of the cells. Engraftment and insulin expression were observed in 63% of VC-02 units explanted from subjects at 3–12 months post-implant. Six of 17 subjects (35.3%) demonstrated positive C-peptide as early as 6 months post-implant. Most reported adverse events were related to surgical implant or explant procedures (27.9%) or to side-effects of immunosuppression (33.7%). Initial data suggest that pluripotent stem cells, which can be propagated to the desired biomass and differentiated into pancreatic islet-like tissue, may offer a scalable, renewable alternative to pancreatic islet transplants. [Display omitted] •Findings are shared for the first 17 participants in a phase 1/2 trial of VC-02•This investigational device was implanted into type 1 diabetes patients•VC-02 contains pluripotent stem cell-derived pancreatic endoderm cells•C-peptide levels and insulin expression correlate with engraftment in 63% of subjects Shapiro et al. report preliminary proof-of-concept that in 17 people with type 1 diabetes, pancreatic endoderm cells in an investigational subcutaneous device (VC-02) achieved engraftment and insulin expression in 63% of units at 3–12 months post-implant. Pluripotent stem cells may be a scalable, renewable alternative to pancreatic islet transplants.