Insulin Expression and Glucose-Responsive Circulating C-Peptide in Type 1 Diabetes Patients Implanted Subcutaneously with Pluripotent Stem Cell-Derived Pancreatic Endoderm Cells in a Macro-Device

Abstract

Islet transplants offer effective relief from glycemic lability and hypoglycemia in patients with type 1 diabetes (T1D), but limited expertise in islet isolation and the paucity of organ donors make this approach ineffective for broad adoption. Pluripotent stem cells (PSCs) offer an attractive alternate source material as they can be propagated to the desired biomass (scalable and ‘renewable’) and differentiated into pancreatic islet-like tissue. In a first-in-human clinical trial, human PSC-derived pancreatic endoderm cells (PEC-01) were implanted subcutaneously in macro delivery devices that allow for direct vascularization in patients with T1D. Units explanted from select trial subjects at latencies from 3 to 12 months post-implant showed substantial cell engraftment and insulin expression. These same subjects who showed substantial cell engraftment also had glucose- and/or mixed meal-responsive C-peptide measured in their blood at latencies from 6 to 21 months, suggesting that, for the first time in human subjects with T1D, when PSC-derived pancreatic endoderm cells are successfully engrafted, they express and release measurable insulin as intended in a physiologically regulated fashion. Funding Statement: Funding sources for this work included the California Institute for Regenerative Medicine, the JDRF, and the Stem Cell Network of Canada. Declaration of Interests: The authors declare no conflicts of interest. MD, RMW, EJK, EPB, KAD, and HLF may have equity interest in ViaCyte, Inc., a privately-held company. Ethics Approval Statement: The authors stated that: All work described herein was performed under proper Investigational Review Board or equivalent ethics committee approval.