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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

19 Pages Posted: 17 Dec 2019

See all articles by AM James Shapiro

AM James Shapiro

University of Alberta - Department of Surgery

David Thompson

University of British Columbia (UBC) - Department of Medicine

Thomas W. Donner

Johns Hopkins University, School of Medicine, Division of Endocrinology, Diabetes, & Metabolism

Melena D. Bellin

University of Minnesota - Minneapolis

Willa Hsueh

Ohio State University (OSU)

Jeremy H. Pettus

University of California, San Diego (UCSD) - Department of Medicine

Jon S. Wilensky

Scripps Memorial Hospital

Mark Daniels

ViaCyte Inc.

Richard M. Wang

ViaCyte Inc.

Evert J. Kroon

ViaCyte Inc.

Eugene Paul Brandon

ViaCyte Inc.

Kevin A. D'Amour

ViaCyte Inc.

Howard Foyt

ViaCyte Inc.

More...

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."

Keywords: diabetes; stem cell; human trial; C-peptide; insulin

Suggested Citation

Shapiro, AM James and Thompson, David and Donner, Thomas W. and Bellin, Melena D. and Hsueh, Willa and Pettus, Jeremy H. and Wilensky, Jon S. and Daniels, Mark and Wang, Richard M. and Kroon, Evert J. and Brandon, Eugene Paul and D'Amour, Kevin A. and Foyt, Howard, 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 (December 9, 2019). Available at SSRN: https://ssrn.com/abstract=3501034 or http://dx.doi.org/10.2139/ssrn.3501034

AM James Shapiro

University of Alberta - Department of Surgery

Canada

David Thompson

University of British Columbia (UBC) - Department of Medicine

2775 Laurel Street, 10th Floor
Vancouver, British Columbia V5Z 1M9
Canada

Thomas W. Donner

Johns Hopkins University, School of Medicine, Division of Endocrinology, Diabetes, & Metabolism

MD
United States

Melena D. Bellin

University of Minnesota - Minneapolis

110 Wulling Hall, 86 Pleasant St, S.E.
308 Harvard Street SE
Minneapolis, MN 55455
United States

Willa Hsueh

Ohio State University (OSU)

Blankenship Hall-2010
901 Woody Hayes Drive
Columbus, OH OH 43210
United States

Jeremy H. Pettus

University of California, San Diego (UCSD) - Department of Medicine

9500 Gilman Drive
La Jolla, CA 92093
United States

Jon S. Wilensky

Scripps Memorial Hospital

La Jolla, CA
United States

Mark Daniels

ViaCyte Inc.

San Diego, CA
United States

Richard M. Wang

ViaCyte Inc.

San Diego, CA
United States

Evert J. Kroon

ViaCyte Inc.

San Diego, CA
United States

Eugene Paul Brandon

ViaCyte Inc.

San Diego, CA
United States

Kevin A. D'Amour

ViaCyte Inc.

San Diego, CA
United States

Howard Foyt (Contact Author)

ViaCyte Inc. ( email )

San Diego, CA
United States