Implanted pluripotent stem-cell-derived pancreatic endoderm cells secrete glucose-responsive C-peptide in patients with type 1 diabetes
Adam Ramzy, David M Thompson, Kirsten A Ward-Hartstonge, Sabine Ivison, Laura Cook, Rosa V Garcia, Jackson Loyal, Peter T W Kim, Garth L Warnock, Megan K Levings, Timothy J Kieffer, Adam Ramzy, David M Thompson, Kirsten A Ward-Hartstonge, Sabine Ivison, Laura Cook, Rosa V Garcia, Jackson Loyal, Peter T W Kim, Garth L Warnock, Megan K Levings, Timothy J Kieffer
Abstract
An open-label, first-in-human phase 1/2 study is being conducted to evaluate the safety and efficacy of pancreatic endoderm cells (PECs) implanted in non-immunoprotective macroencapsulation devices for the treatment of type 1 diabetes. We report an analysis on 1 year of data from the first cohort of 15 patients from a single trial site that received subcutaneous implantation of cell products combined with an immunosuppressive regimen. Implants were well tolerated with no teratoma formation or severe graft-related adverse events. After implantation, patients had increased fasting C-peptide levels and increased glucose-responsive C-peptide levels and developed mixed meal-stimulated C-peptide secretion. There were immunosuppression-related transient increases in circulating regulatory T cells, PD1high T cells, and IL17A+CD4+ T cells. Explanted grafts contained cells with a mature β cell phenotype that were immunoreactive for insulin, islet amyloid polypeptide, and MAFA. These data, and associated findings (Shapiro et al., 2021), are the first reported evidence of meal-regulated insulin secretion by differentiated stem cells in patients.
Trial registration: ClinicalTrials.gov NCT03163511.
Keywords: C-peptide; cell therapy; diabetes; embryonic stem cells; islet transplantation; pancreatic endoderm cells.
Conflict of interest statement
Declaration of interests T.J.K. has received research funding from CRISPR Therapeutics, funding and research contracts from Aspect Biosystems, consulting fees from Sigilon Therapeutics, and research support from ViaCyte, Inc. and has filed patent applications related to the subject of this manuscript. M.K.L. has received research funding from CRISPR Therapeutics. Subsequent to the completion and submission of this manuscript, T.J.K. became an employee of ViaCyte, Inc.
Copyright © 2021 Elsevier Inc. All rights reserved.
Source: PubMed