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Intercommunication between Immune Cells and Mesenchymal Stem Cells in Regenerative Medicine

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".

Deadline for manuscript submissions: closed (30 December 2023) | Viewed by 2872

Special Issue Editor

Dr. Young Woo Eom

E-Mail Website
Guest Editor
1. Cell Therapy and Tissue Engineering Center, Yonsei University Wonju College of Medicine, Wonju, Gangwon-do 26426, Republic of Korea
2. Regeneration Medicine Research Center, Yonsei University Wonju College of Medicine, Wonju, Gangwon-do 26426, Republic of Korea
Interests: mesenchymal stem cells; cell therapy; liver cirrhosis; liver organoid; macrophages; mitochondria transfer

Special Issue Information

Dear Colleagues,

In regenerative medicine, mesenchymal stem cells are known to alleviate inflammatory responses by regulating the activity of various inflammatory cells. It is reported that mesenchymal stem cells regulate inflammatory responses by expressing IDO, PGE2, HGF, TSG-6, etc., but their expression is significantly induced when mesenchymal stem cells are exposed to inflammatory cells or an inflammatory microenvironment. Therefore, understanding the mutual communication between mesenchymal stem cells and immune cells or between mesenchymal stem cells and cytokines is very helpful in understanding the mechanism of action of mesenchymal stem cells in regenerative medicine.

Dr. Young Woo Eom
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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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.

Published Papers (3 papers)

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Research

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12 pages, 2377 KiB  
Communication
Mesenchymal Stem/Stromal Cells Induce Myeloid-Derived Suppressor Cells in the Bone Marrow via the Activation of the c-Jun N-Terminal Kinase Signaling Pathway
by Hyun Ju Lee and Joo Youn Oh
Int. J. Mol. Sci. 2024, 25(2), 1119; https://doi.org/10.3390/ijms25021119 - 17 Jan 2024
Viewed by 664
Abstract
Our previous study demonstrated that mesenchymal stem/stromal cells (MSCs) induce the differentiation of myeloid-derived suppressor cells (MDSCs) in the bone marrow (BM) under inflammatory conditions. In this study, we aimed to investigate the signaling pathway involved. RNA-seq revealed that the mitogen-activated protein kinase [...] Read more.
Our previous study demonstrated that mesenchymal stem/stromal cells (MSCs) induce the differentiation of myeloid-derived suppressor cells (MDSCs) in the bone marrow (BM) under inflammatory conditions. In this study, we aimed to investigate the signaling pathway involved. RNA-seq revealed that the mitogen-activated protein kinase (MAPK) pathway exhibited the highest number of upregulated genes in MSC-induced MDSCs. Western blot analysis confirmed the strong phosphorylation of c-Jun N-terminal kinase (JNK) in BM cells cocultured with MSCs under granulocyte-macrophage colony-stimulating factor stimulation, whereas p38 kinase activation remained unchanged in MSC-cocultured BM cells. JNK inhibition by SP600125 abolished the expression of Arg1 and Nos2, hallmark genes of MDSCs, as well as Hif1a, a molecule mediating monocyte functional reprogramming toward a suppressive phenotype, in MSC-cocultured BM cells. JNK inhibition also abrogated the effects of MSCs on the production of TGF-β1, TGF-β2 and IL-10 in BM cells. Furthermore, JNK inhibition increased Tnfa expression, while suppressing IL-10 production, in MSC-cocultured BM cells in response to lipopolysaccharides. Collectively, our results suggest that MSCs induce MDSC differentiation and promote immunoregulatory cytokine production in BM cells during inflammation, at least in part, through the activation of the JNK–MAPK signaling pathway. Full article
(This article belongs to the Special Issue Intercommunication between Immune Cells and Mesenchymal Stem Cells in Regenerative Medicine)
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15 pages, 2506 KiB  
Article
Role of TGF-β and p38 MAPK in TSG-6 Expression in Adipose Tissue-Derived Stem Cells In Vitro and In Vivo
by Hye Youn Kwon, Yongdae Yoon, Ju-Eun Hong, Ki-Jong Rhee, Joon Hyung Sohn, Pil Young Jung, Moon Young Kim, Soon Koo Baik, Hoon Ryu and Young Woo Eom
Int. J. Mol. Sci. 2024, 25(1), 477; https://doi.org/10.3390/ijms25010477 - 29 Dec 2023
Viewed by 690
Abstract
Mesenchymal stem cells (MSCs) regulate immune cell activity by expressing tumor necrosis factor-α (TNF-α)-stimulated gene 6 (TSG-6) in inflammatory environments; however, whether anti-inflammatory responses affect TSG-6 expression in MSCs is not well understood. Therefore, we investigated whether transforming growth factor-β (TGF-β) regulates TSG-6 [...] Read more.
Mesenchymal stem cells (MSCs) regulate immune cell activity by expressing tumor necrosis factor-α (TNF-α)-stimulated gene 6 (TSG-6) in inflammatory environments; however, whether anti-inflammatory responses affect TSG-6 expression in MSCs is not well understood. Therefore, we investigated whether transforming growth factor-β (TGF-β) regulates TSG-6 expression in adipose tissue-derived stem cells (ASCs) and whether effective immunosuppression can be achieved using ASCs and TGF-β signaling inhibitor A83-01. TGF-β significantly decreased TSG-6 expression in ASCs, but A83-01 and the p38 inhibitor SB202190 significantly increased it. However, in septic C57BL/6 mice, A83-01 further reduced the survival rate of the lipopolysaccharide (LPS)-treated group and ASC transplantation did not improve the severity induced by LPS. ASC transplantation alleviated the severity of sepsis induced by LPS+A83-01. In co-culture of macrophages and ASCs, A83-01 decreased TSG-6 expression whereas A83-01 and SB202190 reduced Cox-2 and IDO-2 expression in ASCs. These results suggest that TSG-6 expression in ASCs can be regulated by high concentrations of pro-inflammatory cytokines in vitro and in vivo, and that A83-01 and SB202190 can reduce the expression of immunomodulators in ASCs. Therefore, our data suggest that co-treatment of ASCs with TGF-β or p38 inhibitors is not adequate to modulate inflammation. Full article
(This article belongs to the Special Issue Intercommunication between Immune Cells and Mesenchymal Stem Cells in Regenerative Medicine)
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Review

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28 pages, 1302 KiB  
Review
Mesenchymal Stromal Cells Derived from Dental Tissues: Immunomodulatory Properties and Clinical Potential
by Luis Ignacio Poblano-Pérez, Marta Elena Castro-Manrreza, Patricia González-Alva, Guadalupe R. Fajardo-Orduña and Juan José Montesinos
Int. J. Mol. Sci. 2024, 25(4), 1986; https://doi.org/10.3390/ijms25041986 - 06 Feb 2024
Viewed by 1156
Abstract
Mesenchymal stem/stromal cells (MSCs) are multipotent cells located in different areas of the human body. The oral cavity is considered a potential source of MSCs because they have been identified in several dental tissues (D-MSCs). Clinical trials in which cells from these sources [...] Read more.
Mesenchymal stem/stromal cells (MSCs) are multipotent cells located in different areas of the human body. The oral cavity is considered a potential source of MSCs because they have been identified in several dental tissues (D-MSCs). Clinical trials in which cells from these sources were used have shown that they are effective and safe as treatments for tissue regeneration. Importantly, immunoregulatory capacity has been observed in all of these populations; however, this function may vary among the different types of MSCs. Since this property is of clinical interest for cell therapy protocols, it is relevant to analyze the differences in immunoregulatory capacity, as well as the mechanisms used by each type of MSC. Interestingly, D-MSCs are the most suitable source for regenerating mineralized tissues in the oral region. Furthermore, the clinical potential of D-MSCs is supported due to their adequate capacity for proliferation, migration, and differentiation. There is also evidence for their potential application in protocols against autoimmune diseases and other inflammatory conditions due to their immunosuppressive capacity. Therefore, in this review, the immunoregulatory mechanisms identified at the preclinical level in combination with the different types of MSCs found in dental tissues are described, in addition to a description of the clinical trials in which MSCs from these sources have been applied. Full article
(This article belongs to the Special Issue Intercommunication between Immune Cells and Mesenchymal Stem Cells in Regenerative Medicine)
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