Mesenchymal stromal cells 2.0: thinking outside the box

Mesenchymal stromal cells (MSCs) are non-hematopoietic progenitor cells that can be derived from a variety of sources including bone marrow and adipose tissues among others. MSCs are plastic adherent and easy to culture ex vivo, making them attractive platforms for cell-based technologies. They have...

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Main Authors: Gabrielle A. Mandl, Malak Lahrichi, Perla Matar, Jamilah Abusarah, Roudy Farah, Jean Pierre Bikorimana, Abba Cisse, Moutih Rafei
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-08-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1657048/full
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author Gabrielle A. Mandl
Malak Lahrichi
Perla Matar
Jamilah Abusarah
Roudy Farah
Jean Pierre Bikorimana
Abba Cisse
Moutih Rafei
Moutih Rafei
Moutih Rafei
author_facet Gabrielle A. Mandl
Malak Lahrichi
Perla Matar
Jamilah Abusarah
Roudy Farah
Jean Pierre Bikorimana
Abba Cisse
Moutih Rafei
Moutih Rafei
Moutih Rafei
author_sort Gabrielle A. Mandl
collection DOAJ
description Mesenchymal stromal cells (MSCs) are non-hematopoietic progenitor cells that can be derived from a variety of sources including bone marrow and adipose tissues among others. MSCs are plastic adherent and easy to culture ex vivo, making them attractive platforms for cell-based technologies. They have an impressive immunoplasticity and can express a suppressive or inflammatory phenotype depending on their stimuli. While MSCs are mainly used in tissue regeneration or as a tool to suppress unwanted inflammation, their pro-inflammatory phenotype includes their ability to act as antigen presenting cells (APCs). This property, along with their ease of expansion and manipulation, make them excellent candidates as alternatives to dendritic cell-based technologies, especially for cancer vaccination. To generate stable MSCs with an APC-like phenotype, two main venues have been explored: genetic and pharmacological reprogramming. Routes to generating MSC-APCs have shown great promise in therapeutic and prophylactic settings in vivo, demonstrating effective tumor control in multiple murine models. Mechanistically, MSC-APCs appear to be generated in response to reactive oxygen species and endoplasmic reticulum stress. While much remains to be uncovered with respect to their phenotype, these reprogrammed cells show great promise as the next generation of cancer vaccine platforms. Herein, we describe the state-of-the-art in routes to reprogramming MSCs and discuss their future in the immune-oncology space as potent cancer vaccines.
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spelling doaj-art-dfa764926f0b4b838bdf1c104e5c73e42025-08-20T04:14:10ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-08-011610.3389/fimmu.2025.16570481657048Mesenchymal stromal cells 2.0: thinking outside the boxGabrielle A. Mandl0Malak Lahrichi1Perla Matar2Jamilah Abusarah3Roudy Farah4Jean Pierre Bikorimana5Abba Cisse6Moutih Rafei7Moutih Rafei8Moutih Rafei9Department of Pharmacology and Physiology, Université de Montréal, Montreal, QC, CanadaMolecular Biology Program, Université de Montréal, Montreal, QC, CanadaDepartment of Microbiology, Infectious Diseases, and Immunology, Université de Montréal, Montreal, QC, CanadaDepartment of Pharmacology and Physiology, Université de Montréal, Montreal, QC, CanadaDepartment of Microbiology, Infectious Diseases, and Immunology, Université de Montréal, Montreal, QC, CanadaDepartment of Microbiology, Infectious Diseases, and Immunology, Université de Montréal, Montreal, QC, CanadaDepartment of Pharmacology and Physiology, Université de Montréal, Montreal, QC, CanadaDepartment of Pharmacology and Physiology, Université de Montréal, Montreal, QC, CanadaMolecular Biology Program, Université de Montréal, Montreal, QC, CanadaDepartment of Microbiology, Infectious Diseases, and Immunology, Université de Montréal, Montreal, QC, CanadaMesenchymal stromal cells (MSCs) are non-hematopoietic progenitor cells that can be derived from a variety of sources including bone marrow and adipose tissues among others. MSCs are plastic adherent and easy to culture ex vivo, making them attractive platforms for cell-based technologies. They have an impressive immunoplasticity and can express a suppressive or inflammatory phenotype depending on their stimuli. While MSCs are mainly used in tissue regeneration or as a tool to suppress unwanted inflammation, their pro-inflammatory phenotype includes their ability to act as antigen presenting cells (APCs). This property, along with their ease of expansion and manipulation, make them excellent candidates as alternatives to dendritic cell-based technologies, especially for cancer vaccination. To generate stable MSCs with an APC-like phenotype, two main venues have been explored: genetic and pharmacological reprogramming. Routes to generating MSC-APCs have shown great promise in therapeutic and prophylactic settings in vivo, demonstrating effective tumor control in multiple murine models. Mechanistically, MSC-APCs appear to be generated in response to reactive oxygen species and endoplasmic reticulum stress. While much remains to be uncovered with respect to their phenotype, these reprogrammed cells show great promise as the next generation of cancer vaccine platforms. Herein, we describe the state-of-the-art in routes to reprogramming MSCs and discuss their future in the immune-oncology space as potent cancer vaccines.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1657048/fullmesenchymal stromal cellscancerimmunotherapyvaccineantigen-presenting cells
spellingShingle Gabrielle A. Mandl
Malak Lahrichi
Perla Matar
Jamilah Abusarah
Roudy Farah
Jean Pierre Bikorimana
Abba Cisse
Moutih Rafei
Moutih Rafei
Moutih Rafei
Mesenchymal stromal cells 2.0: thinking outside the box
Frontiers in Immunology
mesenchymal stromal cells
cancer
immunotherapy
vaccine
antigen-presenting cells
title Mesenchymal stromal cells 2.0: thinking outside the box
title_full Mesenchymal stromal cells 2.0: thinking outside the box
title_fullStr Mesenchymal stromal cells 2.0: thinking outside the box
title_full_unstemmed Mesenchymal stromal cells 2.0: thinking outside the box
title_short Mesenchymal stromal cells 2.0: thinking outside the box
title_sort mesenchymal stromal cells 2 0 thinking outside the box
topic mesenchymal stromal cells
cancer
immunotherapy
vaccine
antigen-presenting cells
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1657048/full
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