ECM Proteins Nidogen-1 and Decorin Restore Functionality of Human Islets of Langerhans upon Hypoxic Conditions.

Autor: Jeyagaran A; Institute of Biomedical Engineering, Department for Medical Technologies and Regenerative Medicine, Eberhard Karls University Tübingen, 72076, Tübingen, Germany., Urbanczyk M; Institute of Biomedical Engineering, Department for Medical Technologies and Regenerative Medicine, Eberhard Karls University Tübingen, 72076, Tübingen, Germany., Carvajal-Berrio D; Institute of Biomedical Engineering, Department for Medical Technologies and Regenerative Medicine, Eberhard Karls University Tübingen, 72076, Tübingen, Germany., Baldissera T; Institute of Biomedical Engineering, Department for Medical Technologies and Regenerative Medicine, Eberhard Karls University Tübingen, 72076, Tübingen, Germany., Kaiser PD; NMI Natural and Medical Sciences Institute at the University of Tübingen, 72770, Reutlingen, Germany., Kuhlburger L; Quantitative Biology Center (QBiC), Eberhard Karls University of Tübingen, 72076, Tübingen, Germany.; Biomedical Data Science, Department of Computer Science, Eberhard Karls University Tübingen, 72076, Arkansas, Germany., Czemmel S; Quantitative Biology Center (QBiC), Eberhard Karls University of Tübingen, 72076, Tübingen, Germany., Nahnsen S; Quantitative Biology Center (QBiC), Eberhard Karls University of Tübingen, 72076, Tübingen, Germany.; Biomedical Data Science, Department of Computer Science, Eberhard Karls University Tübingen, 72076, Arkansas, Germany., Duffy GP; Discipline of Anatomy and the Regenerative Medicine Institute, School of Medicine, College of Medicine Nursing and Health Sciences, National University of Ireland Galway, Galway, H91 TK33, Ireland.; Science Foundation Ireland (SFI) Centre for Research in Advanced Materials for Biomedical Engineering (AMBER), Trinity College Dublin & National University of Ireland Galway, Galway, H91 TK33, Ireland., Brucker SY; Department of Women's Health Tübingen, University of Tübingen, 72076, Tübingen, Germany., Layland SL; Institute of Biomedical Engineering, Department for Medical Technologies and Regenerative Medicine, Eberhard Karls University Tübingen, 72076, Tübingen, Germany.; Department of Women's Health Tübingen, University of Tübingen, 72076, Tübingen, Germany., Schenke-Layland K; Institute of Biomedical Engineering, Department for Medical Technologies and Regenerative Medicine, Eberhard Karls University Tübingen, 72076, Tübingen, Germany.; NMI Natural and Medical Sciences Institute at the University of Tübingen, 72770, Reutlingen, Germany.
Jazyk: angličtina
Zdroj: Advanced healthcare materials [Adv Healthc Mater] 2024 Nov 07, pp. e2403017. Date of Electronic Publication: 2024 Nov 07.
DOI: 10.1002/adhm.202403017
Abstrakt: Transplantation of donor islets of Langerhans is a potential therapeutic approach for patients with diabetes mellitus; however, its success is limited by islet death and dysfunction during the initial hypoxic conditions at the transplantation site. This highlights the need to support the donor islets in the days post-transplantation until the site is vascularized. It was previously demonstrated that the extracellular matrix (ECM) proteins nidogen-1 (NID1) and decorin (DCN) improve the functionality and survival of the β-cell line, EndoC-βH3, and the viability of human islets post-isolation. To advance the use of these ECM proteins toward a clinical application and elucidate the mechanisms of action in primary islets, the study assesses the effects of ECM proteins NID1 and DCN on isolated human donor islets cultured in normoxic and hypoxic conditions. NID1- and DCN-treatment restore β-cell functionality of human donor islets in a hypoxic environment through upregulation of genes involved in glycolytic pathways and reducing DNA fragmentation in hypoxic conditions comparable to normoxic control islets. The results demonstrate that the utilization of NID1 or DCN with islets of Langerhans may have the potential to overcome the hypoxia-induced cell death observed post-transplantation and improve transplant outcomes.
(© 2024 The Author(s). Advanced Healthcare Materials published by Wiley‐VCH GmbH.)
Databáze: MEDLINE
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