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Cells
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Molecular and Cellular Mechanisms underlying the Immunomodulatory Potential of Mesenchymal...
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Molecular and Cellular Mechanisms underlying the Immunomodulatory Potential of Mesenchymal Stromal Cells

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Immunology".

Deadline for manuscript submissions: closed (30 June 2022) | Viewed by 7298

Special Issue Editor

Dr. Selim Kuçi

E-Mail Website
Guest Editor
University Hospital for Children and Adolescents, Division for Stem Cell Transplantation andImmunology, MSC-Laboratory, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany
Interests: mesenchymal stromal cells and their subsets; hematopoiesis; regenerative medicine

Special Issue Information

Dear Colleagues,

Mesenchymal stromal Cells (MSCs) are multipotent non-hematopoietic cells which exert a myriad of functions through cell-cell contact or secretion of a plethora of molecules (PGE2, IDO, HGF, IL-10, HLA-G, miRNAs, metabolites etc.) which can also be transported by extracellular vesicles to the target tissues. These molecules may either directly affect function of cells of innate and adaptive immunity or indirectly by acting on cell populations (T-regulatory cells, T cells producing GM-CSF, coronin-1a expressing T cells, regulatory monocytes etc.), which in turn themselves may modulate the immune response. Based on their immunosuppressive properties, MSCs hold great promise in the treatment of immune disorders such as graft-versus-host disease and many other inflammatory disorders in the organism. This special issue should provide more insights into the most currently uncovered mechanisms of action which mediate the cross-talk of MSCs with the cells of immune system in a preclinical and clinical setting.

Dr. Selim Kuçi
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Mesenchymal stromal/stem cells
  • Secretome
  • Extracellular vesicles
  • Exosomes
  • miRNAs
  • metabolome
  • mechanism of action (MoA)
  • preclinical and clinical immunomodulation

Published Papers (2 papers)

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Research

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18 pages, 3886 KiB  
Article
Cytokines Differently Define the Immunomodulation of Mesenchymal Stem Cells from the Periodontal Ligament
by Christian Behm, Alice Blufstein, Johannes Gahn, Michael Nemec, Andreas Moritz, Xiaohui Rausch-Fan and Oleh Andrukhov
Cells 2020, 9(5), 1222; https://doi.org/10.3390/cells9051222 - 14 May 2020
Cited by 24 | Viewed by 3977
Abstract
Human periodontal ligament stem cells (hPDLSCs) play an important role in periodontal tissue homeostasis and regeneration. The function of these cells in vivo depends largely on their immunomodulatory ability, which is reciprocally regulated by immune cells via cytokines, particularly interferon (IFN)-γ, tumor necrosis [...] Read more.
Human periodontal ligament stem cells (hPDLSCs) play an important role in periodontal tissue homeostasis and regeneration. The function of these cells in vivo depends largely on their immunomodulatory ability, which is reciprocally regulated by immune cells via cytokines, particularly interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and interleukin (IL)-1β. Different cytokines activate distinct signaling pathways and might differently affect immunomodulatory activities of hPDLSCs. This study directly compared the effect of IFN-γ, TNF-α, or IL-1β treated primary hPDLSCs on allogenic CD4+ T lymphocyte proliferation and apoptosis in an indirect co-culture model. The effects of IFN-γ, TNF-α, and IL-1β on the expression of specific immunomodulatory factors such as intoleamine-2,3-dioxygenase-1 (IDO-1), prostaglandin E2 (PGE2), and programmed cell death 1 ligand 1 (PD-L1) and ligand 2 (PD-L2) in hPDLSCs were compared. The contribution of different immunomodulatory mediators to the immunomodulatory effects of hPDLSCs in the indirect co-culture experiments was assessed using specific inhibitors. Proliferation of CD4+ T lymphocytes was inhibited by hPDLSCs, and this effect was strongly enhanced by IFN-γ and IL-1β but not by TNF-α. Apoptosis of CD4+ T lymphocytes was decreased by hPDLSCs per se. This effect was counteracted by IFN-γ or IL-1β. Additionally, IFN-γ, TNF-α, and IL-1β differently regulated all investigated immunomediators in hPDLSCs. Pharmacological inhibition of immunomediators showed that their contribution in regulating CD4+ T lymphocytes depends on the cytokine milieu. Our data indicate that inflammatory cytokines activate specific immunomodulatory mechanisms in hPDLSCs and the expression of particular immunomodulatory factors, which underlies a complex reciprocal interaction between hPDLSCs and CD4+ T lymphocytes. Full article
(This article belongs to the Special Issue Molecular and Cellular Mechanisms underlying the Immunomodulatory Potential of Mesenchymal Stromal Cells)
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Review

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16 pages, 1247 KiB  
Review
Mesenchymal Stem Cells in Embryo-Maternal Communication under Healthy Conditions or Viral Infections: Lessons from a Bovine Model
by Alexandra Calle and Miguel Ángel Ramírez
Cells 2022, 11(12), 1858; https://doi.org/10.3390/cells11121858 - 7 Jun 2022
Cited by 2 | Viewed by 2765
Abstract
Bovine mesenchymal stem cells are a relevant cell population found in the maternal reproductive tract that exhibits the immunomodulation capacity required to prevent embryo rejection. The phenotypic plasticity showed by both endometrial mesenchymal stem cells (eMSC) and embryonic trophoblast through mesenchymal to epithelial [...] Read more.
Bovine mesenchymal stem cells are a relevant cell population found in the maternal reproductive tract that exhibits the immunomodulation capacity required to prevent embryo rejection. The phenotypic plasticity showed by both endometrial mesenchymal stem cells (eMSC) and embryonic trophoblast through mesenchymal to epithelial transition and epithelial to mesenchymal transition, respectively, is essential for embryo implantation. Embryonic trophoblast maintains active crosstalk via EVs and soluble proteins with eMSC and peripheral blood MSC (pbMSC) to ensure the retention of eMSC in case of pregnancy and induce the chemotaxis of pbMSC, critical for successful implantation. Early pregnancy-related proteins and angiogenic markers are detected as cargo in EVs and the soluble fraction of the embryonic trophectoderm secretome. The pattern of protein secretion in trophectoderm-EVs changes depending on their epithelial or mesenchymal phenotype and due to the uptake of MSC EVs. However, the changes in this EV-mediated communication between maternal and embryonic MSC populations infected by viruses that cause abortions in cattle are poorly understood. They are critical in the investigation of reproductive viral pathologies. Full article
(This article belongs to the Special Issue Molecular and Cellular Mechanisms underlying the Immunomodulatory Potential of Mesenchymal Stromal Cells)
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