Implanted pluripotent stem-cell-derived pancreatic endoderm cells secrete glucose-responsive C-peptide in patients with type 1 diabetes.

C-Peptide Cell Differentiation Diabetes Mellitus, Type 1 / therapy Endoderm Glucose Humans Insulin Insulin-Secreting Cells
C-peptide cell therapy diabetes embryonic stem cells islet transplantation pancreatic endoderm cells

Journal

Cell stem cell
ISSN: 1875-9777
Titre abrégé: Cell Stem Cell
Pays: United States
ID NLM: 101311472

Informations de publication

Date de publication:
02 12 2021
Historique:
received: 03 12 2020
revised: 29 04 2021
accepted: 08 10 2021
entrez: 3 12 2021
pubmed: 4 12 2021
medline: 8 1 2022
Statut: ppublish

Résumé

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, PD1

Identifiants

DOI: 10.1016/j.stem.2021.10.003 PMID: 34861146
pubmed: 34861146
pii: S1934-5909(21)00415-X
doi: 10.1016/j.stem.2021.10.003
pii:
doi:

Substances chimiques

C-Peptide 0
Insulin 0
Glucose IY9XDZ35W2

Banques de données

ClinicalTrials.gov
['NCT03163511']

Types de publication

Clinical Trial, Phase I Clinical Trial, Phase II Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2047-2061.e5

Subventions

Organisme : CIHR
Pays : Canada

Commentaires et corrections

Type : CommentIn
Type : CommentIn
Type : CommentIn

Informations de copyright

Copyright © 2021 Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

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.

Auteurs

Adam Ramzy (A)

Laboratory of Molecular and Cellular Medicine, Department of Cellular and Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.

David M Thompson (DM)

Division of Endocrinology, Department of Medicine, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.

Kirsten A Ward-Hartstonge (KA)

Department of Surgery, University of British Columbia, Vancouver, BC V6T 1Z3, Canada; BC Children's Hospital Research Institute (BCCHRI), Vancouver, BC V5Z 4H4, Canada.

Sabine Ivison (S)

Department of Surgery, University of British Columbia, Vancouver, BC V6T 1Z3, Canada; BC Children's Hospital Research Institute (BCCHRI), Vancouver, BC V5Z 4H4, Canada.

Laura Cook (L)

Department of Surgery, University of British Columbia, Vancouver, BC V6T 1Z3, Canada; BC Children's Hospital Research Institute (BCCHRI), Vancouver, BC V5Z 4H4, Canada.

Rosa V Garcia (RV)

Department of Surgery, University of British Columbia, Vancouver, BC V6T 1Z3, Canada; BC Children's Hospital Research Institute (BCCHRI), Vancouver, BC V5Z 4H4, Canada.

Jackson Loyal (J)

Division of Endocrinology, Department of Medicine, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.

Peter T W Kim (PTW)

Department of Surgery, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.

Garth L Warnock (GL)

Department of Surgery, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.

Megan K Levings (MK)

Department of Surgery, University of British Columbia, Vancouver, BC V6T 1Z3, Canada; BC Children's Hospital Research Institute (BCCHRI), Vancouver, BC V5Z 4H4, Canada; School of Biomedical Engineering, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.

Timothy J Kieffer (TJ)

Laboratory of Molecular and Cellular Medicine, Department of Cellular and Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, BC V6T 1Z3, Canada; Department of Surgery, University of British Columbia, Vancouver, BC V6T 1Z3, Canada; School of Biomedical Engineering, University of British Columbia, Vancouver, BC V6T 1Z3, Canada. Electronic address: tim.kieffer@ubc.ca.

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Classifications MeSH

questionsmedicales.fr › Acides aminés, peptides et protéines › Peptides › Hormones peptidiques › Hormones pancréatiques › Insulines › Peptide C › Implanted pluripotent stem-cell-derived...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Différenciation cellulaire › Implanted pluripotent stem-cell-derived...
questionsmedicales.fr › Maladies du système immunitaire › Maladies auto-immunes › Diabète de type 1 › Implanted pluripotent stem-cell-derived...
questionsmedicales.fr › Structures de l'embryon › Feuillets embryonnaires › Endoderme › Implanted pluripotent stem-cell-derived...
questionsmedicales.fr › Glucides › Sucres › Oses › Hexose › Glucose › Implanted pluripotent stem-cell-derived...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Implanted pluripotent stem-cell-derived...
questionsmedicales.fr › Acides aminés, peptides et protéines › Peptides › Hormones peptidiques › Hormones pancréatiques › Insulines › Insuline › Implanted pluripotent stem-cell-derived...
questionsmedicales.fr › Cellules › Cellules épithéliales › Cellules entéroendocrines › Cellules à insuline › Implanted pluripotent stem-cell-derived...