The New Era of Mesenchymal Stromal/Stem Cell Functional Application: State of the Art, Therapeutic Challenges and Future Directions

A topical collection in Cells (ISSN 2073-4409). This collection belongs to the section "Cellular Immunology".

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Editors


E-Mail Website
Collection Editor

E-Mail Website
Collection Editor
Laboratory of Clinical Cell Therapy, Jules Bordet Institute, Université Libre de Bruxelles (ULB), Campus Erasme, Bâtiment de Transfusion (Level +1), 1070 Brussels, Belgium
Interests: mesenchymal stem/stromal cells (MSCs); tissue sources of MSCs; immunomodulation properties; extracellular vesicles (EVs); environmental challenges; efficient MSC immunotherapy
Special Issues, Collections and Topics in MDPI journals

Topical Collection Information

Dear Colleagues,

Mesenchymal stromal cells (MSCs) hold great promise in the field of immunotherapy and regenerative medicine. Indeed, a significant amount of experimental evidence supports the notion that MSCs i) can finely regulate both innate and adaptive immune response and ii) may show the property to differentiate into both mature mesodermal and ectodermal cells. However, some conflicting results have been reported on the molecular mechanisms responsible for their immunosuppressive and totipotential properties of differentiation. The specific identification of phenotypic and functional behavior of these cells will further trigger their clinical use for a variety of autoimmune and degenerative diseases. As part of their molecular mechanisms of action, MSCs produce extracellular matrix protein and closely interact with the tissue environment, displaying a combination of trophic and immunomodulatory actions. These therapeutic effects are likely governed by cell-to cell contact, paracrine pathways, including a role for extracellular vesicles (EVs) and their functional plasticity which means they can adapt their behavior in the face of tissue challenges. MSCs can also be present within the tumor microenvironment and influence tumor cell growth and tumor immune response, as well as the therapeutic effect of anti-blastic drugs and immune-checkpoint blockers. 

It is time to bridge MSCs from the bench and clinical applications by translating basic science into medical programs. The great contribution of colleagues involved in the field will significantly enrich the debate and open up new horizons for the use of MSCs. Accordingly, a better knowledge and characterization of the biological and immunological characteristics of MSCs will increase the safety and efficiency of their clinical application.

Prof. Dr. Alessandro Poggi
Dr. Mehdi Najar
Collection Editors

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Keywords

  • MSCs
  • mesenchymal stromal cells
  • immunotherapy
  • regenerative medicine
  • immune
  • tumor

Published Papers (3 papers)

2024

Jump to: 2022

27 pages, 4840 KiB  
Article
Umbilical Cord Mesenchymal Stromal/Stem Cells and Their Interplay with Th-17 Cell Response Pathway
by Mehdi Najar, Saida Rahmani, Wissam H. Faour, Sami G. Alsabri, Catherine A. Lombard, Hussein Fayyad-Kazan, Etienne M. Sokal, Makram Merimi and Hassan Fahmi
Cells 2024, 13(2), 169; https://doi.org/10.3390/cells13020169 - 16 Jan 2024
Viewed by 1294
Abstract
As a form of immunomodulatory therapeutics, mesenchymal stromal/stem cells (MSCs) from umbilical cord (UC) tissue were assessed for their dynamic interplay with the Th-17 immune response pathway. UC-MSCs were able to modulate lymphocyte response by promoting a Th-17-like profile. Such modulation depended on [...] Read more.
As a form of immunomodulatory therapeutics, mesenchymal stromal/stem cells (MSCs) from umbilical cord (UC) tissue were assessed for their dynamic interplay with the Th-17 immune response pathway. UC-MSCs were able to modulate lymphocyte response by promoting a Th-17-like profile. Such modulation depended on the cell ratio of the cocultures as well as the presence of an inflammatory setting underlying their plasticity. UC-MSCs significantly increased the expression of IL-17A and RORγt but differentially modulated T cell expression of IL-23R. In parallel, the secretion profile of the fifteen factors (IL1β, IL-4, IL-6, IL-10, IL-17A, IL-17F, IL-22, IL-21, IL-23, IL-25, IL-31, IL-33, INF-γ, sCD40, and TNF-α) involved in the Th-17 immune response pathway was substantially altered during these cocultures. The modulation of these factors demonstrates the capacity of UC-MSCs to sense and actively respond to tissue challenges. Protein network and functional enrichment analysis indicated that several biological processes, molecular functions, and cellular components linked to distinct Th-17 signaling interactions are involved in several trophic, inflammatory, and immune network responses. These immunological changes and interactions with the Th-17 pathway are likely critical to tissue healing and may help to identify molecular targets that will improve therapeutic strategies involving UC-MSCs. Full article
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Graphical abstract

2022

Jump to: 2024

15 pages, 3267 KiB  
Article
Mesenchymal Stromal Cells-Derived Extracellular Vesicles Regulate Dendritic Cell Functions in Dry Eye Disease
by Rongjie Guo, Qi Liang, Yun He, Chenchen Wang, Jiaxuan Jiang, Taige Chen, Di Zhang and Kai Hu
Cells 2023, 12(1), 33; https://doi.org/10.3390/cells12010033 - 22 Dec 2022
Cited by 7 | Viewed by 2388
Abstract
We explored the therapeutic efficacy of Mesenchymal stromal cells-derived extracellular vesicles (MSC-EVs) and its inhibition of the functions of dendritic cells (DCs) in dry eye disease (DED). MSC-EVs were isolated from the culture supernatants of mesenchymal stromal cells (MSCs) and characterized. In vitro, [...] Read more.
We explored the therapeutic efficacy of Mesenchymal stromal cells-derived extracellular vesicles (MSC-EVs) and its inhibition of the functions of dendritic cells (DCs) in dry eye disease (DED). MSC-EVs were isolated from the culture supernatants of mesenchymal stromal cells (MSCs) and characterized. In vitro, human corneal epithelial cells (HCECs) were cultured in hyperosmotic medium to simulate the DED hyperosmotic environment and treated with MSC-EVs. Cell viability was assessed, and the expression of inflammatory cytokines was quantified. Next, we induced DED in female C57BL/6 mice and divided the mice into groups treated with either MSC-EVs or phosphate buffer solution (PBS) eye drops. Disease severity was assessed; mRNA expression of inflammatory cytokines was analyzed by RT-PCR; and Th17 cells were detected by flow cytometry. Lastly, we evaluated DCs by immunofluorescence and flow cytometric analysis to assess its amounts and maturation. MSC-EVs showed protective effects on HCECs under hyperosmotic stress in vitro, suppressing the expression of inflammatory cytokines. In vivo, mice topically treated with MSC-Evs presented reduced DED disease severity compared to PBS-treated mice. MSC-Evs downregulated the expression of inflammatory cytokines, including TNF-α, IL-6, and IL-1β, as well as the frequency of Th17 cells. Further investigation showed that MSC-EVs suppressed the increase of amounts and the maturation of DCs in DED. Changes of morphological characters of DCs were also inhibited by MSC-EVs. Our study revealed that MSC-EVs suppressed ocular surface inflammation by inhibiting DCs activation-mediated Th17 immune responses, explicating the therapeutic potential of MSC-EVs in DED and other ocular surface diseases. Full article
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Figure 1

3 pages, 226 KiB  
Editorial
Mesenchymal Stem/Stromal Cells as a Therapeutic Tool in Cell-Based Therapy and Regenerative Medicine: An Introduction Expertise to the Topical Collection
by Makram Merimi, Hassan Fahmi, Joery De Kock, Charline Beguin, Arsène Burny, Guido Moll, Alessandro Poggi and Mehdi Najar
Cells 2022, 11(19), 3158; https://doi.org/10.3390/cells11193158 - 8 Oct 2022
Cited by 7 | Viewed by 1474
Abstract
We are pleased to present this opening editorial, introducing our topical collection, “The New Era of Mesenchymal Stromal/Stem Cell Functional Application: State of the Art, Therapeutic Challenges and Future Directions” [...] Full article
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