Could hypoxic conditioning augment the potential of mesenchymal stromal cell-derived extracellular vesicles as a treatment for type 1 diabetes?

Abstract Type1 Diabetes (T1D) is an autoimmune disorder characterised by the loss of pancreatic β-cells. This β cell loss occurs primarily through inflammatory pathways culminating in apoptosis. Mesenchymal stromal cells (MSCs) have been heavily studied for therapeutic applications due to their rege...

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Main Authors: Cathal Patrick Forkan, Aruna Shrestha, Alfred Yu, Christine Chuang, Flemming Pociot, Reza Yarani
Format: Article
Language:English
Published: BMC 2025-02-01
Series:Stem Cell Research & Therapy
Subjects:
Online Access:https://doi.org/10.1186/s13287-025-04153-4
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author Cathal Patrick Forkan
Aruna Shrestha
Alfred Yu
Christine Chuang
Flemming Pociot
Reza Yarani
author_facet Cathal Patrick Forkan
Aruna Shrestha
Alfred Yu
Christine Chuang
Flemming Pociot
Reza Yarani
author_sort Cathal Patrick Forkan
collection DOAJ
description Abstract Type1 Diabetes (T1D) is an autoimmune disorder characterised by the loss of pancreatic β-cells. This β cell loss occurs primarily through inflammatory pathways culminating in apoptosis. Mesenchymal stromal cells (MSCs) have been heavily studied for therapeutic applications due to their regenerative, anti-apoptotic, immunomodulatory, and anti-inflammatory properties. The therapeutic effects of MSCs are mediated through cell-to-cell contact, differentiation, and the release of paracrine factors, which include the release of extracellular vesicles (EVs). Culturing MSCs in hypoxia, a low oxygen tension state more analogous to their physiological environment, seems to increase the therapeutic efficacy of MSC cell therapy, enhancing their immunomodulatory, anti-inflammatory, and anti-fibrotic properties. This is also the case with MSC-derived EVs, which show altered properties based on the parent cell preconditioning. In this review, we examine the evidence supporting the potential application of hypoxic preconditioning in strengthening MSC-EVs for treating the inflammatory and apoptotic causes of β cell loss in T1D.
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institution Kabale University
issn 1757-6512
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publishDate 2025-02-01
publisher BMC
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series Stem Cell Research & Therapy
spelling doaj-art-d057022e71604cb3ab6ee87242e07c582025-02-09T12:15:47ZengBMCStem Cell Research & Therapy1757-65122025-02-0116111010.1186/s13287-025-04153-4Could hypoxic conditioning augment the potential of mesenchymal stromal cell-derived extracellular vesicles as a treatment for type 1 diabetes?Cathal Patrick Forkan0Aruna Shrestha1Alfred Yu2Christine Chuang3Flemming Pociot4Reza Yarani5Translational Type 1 Diabetes Research, Department of Clinical and Translational Research, Steno Diabetes Center CopenhagenTranslational Type 1 Diabetes Research, Department of Clinical and Translational Research, Steno Diabetes Center CopenhagenInterventional Regenerative Medicine and Imaging Laboratory, Department of Radiology, Stanford University School of MedicineDepartment of Biomedical Sciences, Faculty of Health and Medical Sciences, University of CopenhagenTranslational Type 1 Diabetes Research, Department of Clinical and Translational Research, Steno Diabetes Center CopenhagenTranslational Type 1 Diabetes Research, Department of Clinical and Translational Research, Steno Diabetes Center CopenhagenAbstract Type1 Diabetes (T1D) is an autoimmune disorder characterised by the loss of pancreatic β-cells. This β cell loss occurs primarily through inflammatory pathways culminating in apoptosis. Mesenchymal stromal cells (MSCs) have been heavily studied for therapeutic applications due to their regenerative, anti-apoptotic, immunomodulatory, and anti-inflammatory properties. The therapeutic effects of MSCs are mediated through cell-to-cell contact, differentiation, and the release of paracrine factors, which include the release of extracellular vesicles (EVs). Culturing MSCs in hypoxia, a low oxygen tension state more analogous to their physiological environment, seems to increase the therapeutic efficacy of MSC cell therapy, enhancing their immunomodulatory, anti-inflammatory, and anti-fibrotic properties. This is also the case with MSC-derived EVs, which show altered properties based on the parent cell preconditioning. In this review, we examine the evidence supporting the potential application of hypoxic preconditioning in strengthening MSC-EVs for treating the inflammatory and apoptotic causes of β cell loss in T1D.https://doi.org/10.1186/s13287-025-04153-4Mesenchymal stem cellsNormoxiaHypoxiaExtracellular vesiclesmiRNA
spellingShingle Cathal Patrick Forkan
Aruna Shrestha
Alfred Yu
Christine Chuang
Flemming Pociot
Reza Yarani
Could hypoxic conditioning augment the potential of mesenchymal stromal cell-derived extracellular vesicles as a treatment for type 1 diabetes?
Stem Cell Research & Therapy
Mesenchymal stem cells
Normoxia
Hypoxia
Extracellular vesicles
miRNA
title Could hypoxic conditioning augment the potential of mesenchymal stromal cell-derived extracellular vesicles as a treatment for type 1 diabetes?
title_full Could hypoxic conditioning augment the potential of mesenchymal stromal cell-derived extracellular vesicles as a treatment for type 1 diabetes?
title_fullStr Could hypoxic conditioning augment the potential of mesenchymal stromal cell-derived extracellular vesicles as a treatment for type 1 diabetes?
title_full_unstemmed Could hypoxic conditioning augment the potential of mesenchymal stromal cell-derived extracellular vesicles as a treatment for type 1 diabetes?
title_short Could hypoxic conditioning augment the potential of mesenchymal stromal cell-derived extracellular vesicles as a treatment for type 1 diabetes?
title_sort could hypoxic conditioning augment the potential of mesenchymal stromal cell derived extracellular vesicles as a treatment for type 1 diabetes
topic Mesenchymal stem cells
Normoxia
Hypoxia
Extracellular vesicles
miRNA
url https://doi.org/10.1186/s13287-025-04153-4
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