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Latest Research on Mesenchymal Stem Cells
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Latest Research on Mesenchymal Stem Cells

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

Deadline for manuscript submissions: 20 May 2025 | Viewed by 11138

Special Issue Editor

Prof. Dr. Marcel Costuleanu

E-Mail Website
Guest Editor
Department of Oral and Maxillofacial Surgery, Grigore T Popa University of Medicine and Pharmacy Iaşi, Iasi, Romania
Interests: mesenchymal stem cells; apoptosis; tissue niches; tissue homeostasis; senescence; epigenetics

Special Issue Information

Dear Colleagues,

MSCs (mesenchymal stem/stromal cells) are found in practically all tissues and play a role in regeneration and homeostasis. They have the ability to self-renew and activate multipotency when stimulated by biochemical signals. The MSC secretome or MSC-derived extracellular vesicles (exosomes and microvesicles, EVs) have been hypothesized as a more important biological mechanism contributing to their function than their differentiation capacity. EVs play a role in cell-to-cell communication, cell signaling, and changing cell or tissue metabolism at the local or global level. MSC-derived exosomes contain, e.g., cytokines and growth factors, signaling lipids, mRNAs, and regulatory miRNAs.

The contents of MSC exosomes are dynamic, influenced by the MSC tissue of origin, its activity, and its immediate intercellular neighbors. Thus, when MSCs are grown alongside tumor cells or in the in vivo tumor microenvironment, the exosome concentration appears to be altered. MSCs can directly donate mitochondria to recover from cell injury and rescue mitochondrial damage-induced tissue degeneration. This could promote cancer growth and spread by promoting mitochondrial exchange between cancer cells and adjacent stromal cells. A growing body of evidence implies that physical stimulation has a role in MSC development.

We aim to highlight new areas of research related to MSC involvement in niche-specific development, tissue homeostasis, and function, with emphasis on the molecular level. This research will open the way for deciphering the molecular mysteries of MSCs, as well as for novel therapeutic modalities.

Prof. Dr. Marcel Costuleanu
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.

Keywords

  • mesenchymal stem cell
  • MSC
  • niche
  • tissue homeostasis
  • exosomes
  • microvesicles
  • cancer
  • mitochondrial exchange
  • MSC secretome

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Published Papers (7 papers)

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Research

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14 pages, 4082 KiB  
Article
Ingenol-3-Angelate Enhances the B Cell Inhibitory Potential of Mesenchymal Stem Cells, Leading to Marked Alleviation of Lupus Symptoms in MRL.faslpr Mice
by Hong Kyung Lee, Hwa Kyung Kim, Ji Yeon Kim, Ji Su Kim, JinKyung Park, Min Sung Kim, Tae Yong Lee, Key-Hwan Lim, Hanseul Park, Dong Ju Son, Jin Tae Hong and Sang-Bae Han
Int. J. Mol. Sci. 2024, 25(23), 12625; https://doi.org/10.3390/ijms252312625 - 25 Nov 2024
Viewed by 1109
Abstract
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by autoantibody production by hyper-activated B cells. Although mesenchymal stem cells (MSCs) relieve lupus symptoms by inhibiting mainly T cells, whether MSCs also inhibit B cells has been controversial. Here, we found that [...] Read more.
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by autoantibody production by hyper-activated B cells. Although mesenchymal stem cells (MSCs) relieve lupus symptoms by inhibiting mainly T cells, whether MSCs also inhibit B cells has been controversial. Here, we found that naïve MSCs inhibited IFN-γ production by T cells, but not IgM production by B cells. We used a chemical approach to prime MSCs to inhibit B cells. We found that ingenol-3-angelate (I3A), a non-tumor-promoting phorbol ester, activated MSCs to inhibit B cells in a TGF-β1-dependent manner. We also showed that IL-1β induced MSCs to continuously secrete TGF-β1, which directly inhibited IgM production by B cells, whereas IL-1β did not. I3A-treated MSCs were better than naïve MSCs at ameliorating SLE symptoms in MRL.faslpr mice. In summary, our data provide information on how to generate MSCs that are effective for the treatment of SLE characterized by excessive B cell activation. Full article
(This article belongs to the Special Issue Latest Research on Mesenchymal Stem Cells)
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18 pages, 7406 KiB  
Article
Late Bone Marrow Mononuclear Cell Transplantation in Rats with Sciatic Nerve Crush: Analysis of a Potential Therapeutic Time Window
by Vanina Usach, Mailin Casadei, Gonzalo Piñero, Marianela Vence, Paula Soto, Alicia Cueto, Pablo Rodolfo Brumovsky and Clara Patricia Setton-Avruj
Int. J. Mol. Sci. 2024, 25(23), 12482; https://doi.org/10.3390/ijms252312482 - 21 Nov 2024
Viewed by 1179
Abstract
After peripheral nerve injury, axon and myelin regeneration are key events for optimal clinical improvements. We have previously shown that early bone marrow mononuclear cell (BMMC) transplantation exerts beneficial effects on myelin regeneration. In the present study, we analyze whether there is a [...] Read more.
After peripheral nerve injury, axon and myelin regeneration are key events for optimal clinical improvements. We have previously shown that early bone marrow mononuclear cell (BMMC) transplantation exerts beneficial effects on myelin regeneration. In the present study, we analyze whether there is a temporal window in which BMMCs migrate more efficiently to damaged nerves while still retaining their positive effects. Adult Wistar rats of both sexes, with sciatic nerve crush, were systemically transplanted with BMMC at different days post injury. Vehicle-treated, naïve, and sham rats were also included. Morphological, functional, and behavioral analyses were performed in nerves from each experimental group at different survival times. BMMC transplantation between 0 and 7 days after injury resulted in the largest number of nested cells within the injured sciatic nerve, which supports the therapeutic value of BMMC administration within the first week after injury. Most importantly, later BMMC administration 7 days after sciatic nerve crush was associated with neuropathic pain reversion, improved morphological appearance of the damaged nerves, and a tendency toward faster recovery in the sciatic functional index and electrophysiological parameters. Our results thus support the notion that even delayed BMMC treatment may represent a promising therapeutic strategy for peripheral nerve injuries. Full article
(This article belongs to the Special Issue Latest Research on Mesenchymal Stem Cells)
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21 pages, 5017 KiB  
Article
Novel Gene Biomarkers Specific to Human Mesenchymal Stem Cells Isolated from Bone Marrow
by Sandra Muntión, Elena Sánchez-Luis, María Díez-Campelo, Juan F. Blanco, Fermín Sánchez-Guijo and Javier De Las Rivas
Int. J. Mol. Sci. 2024, 25(22), 11906; https://doi.org/10.3390/ijms252211906 - 6 Nov 2024
Viewed by 1207
Abstract
In this paper, we present a comparative analysis of the transcriptomic profile of three different human cell types: hematopoietic stem cells (HSCs), bone marrow-derived mesenchymal stem cells (MSCs) and fibroblasts (FIBs). The work aims to identify unique genes that are differentially expressed as [...] Read more.
In this paper, we present a comparative analysis of the transcriptomic profile of three different human cell types: hematopoietic stem cells (HSCs), bone marrow-derived mesenchymal stem cells (MSCs) and fibroblasts (FIBs). The work aims to identify unique genes that are differentially expressed as specific markers of bone marrow-derived MSCs, and to achieve this undertakes a detailed analysis of three independent datasets that include quantification of the global gene expression profiles of three primary cell types: HSCs, MSCs and FIBs. A robust bioinformatics method, called GlobalTest, is used to assess the specific association between one or more genes expressed in a sample and the outcome variable, that is, the ‘cell type’ provided as a single univariate response. This outcome variable is predicted for each sample tested, based on the expression profile of the specific genes that are used as input to the test. The precision of the tests is calculated along with the statistical sensitivity and specificity for each gene in each dataset, yielding four genes that mark MSCs with high accuracy. Among these, the best performer is the protein-coding gene Transgelin (TAGLN, Gene ID: 6876) (with a Positive Predictive Value > 0.96 and FDR < 0.001), which identifies MSCs better than any of the currently used standard markers: ENG (CD105), THY1 (CD90) or NT5E (CD73). The results are validated by RT-qPCR, providing novel gene biomarkers specific for human MSCs. Full article
(This article belongs to the Special Issue Latest Research on Mesenchymal Stem Cells)
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16 pages, 5650 KiB  
Article
Definition of Synovial Mesenchymal Stem Cells for Meniscus Regeneration by the Mechanism of Action and General Amp1200 Gene Expression
by Kentaro Nakamura, Tsukasa Kitahashi, Ryo Kogawa, Yuichi Yoshino and Izumi Ogura
Int. J. Mol. Sci. 2024, 25(19), 10510; https://doi.org/10.3390/ijms251910510 - 29 Sep 2024
Viewed by 1248
Abstract
The quality control (QC) of pharmaceutical-grade cell-therapy products, such as mesenchymal stem cells (MSCs), is challenging. Attempts to develop such products have been hampered by difficulties defining cell-type-specific characteristics and therapeutic mechanisms of action (MoAs). Although we have developed a cell therapy product, [...] Read more.
The quality control (QC) of pharmaceutical-grade cell-therapy products, such as mesenchymal stem cells (MSCs), is challenging. Attempts to develop such products have been hampered by difficulties defining cell-type-specific characteristics and therapeutic mechanisms of action (MoAs). Although we have developed a cell therapy product, FF-31501, consisting of human synovial MSCs (SyMSCs), it was difficult to find specific markers for SyMSCs and to define the cells separately from other MSCs. The purpose of this study was to create a method for identifying and defining SyMSCs from other tissue-derived MSCs and to delve deeper into the mechanism of action of SyMSC-induced meniscus regeneration. Specifically, as a cell-type-dependent approach, we constructed a set of 1143 genes (Amp1200) reported to be associated with MSCs and established a method to evaluate them by correlating gene expression patterns. As a result, it was possible to define SyMSCs separately from other tissue-derived MSCs and non-MSCs. In addition, the gene expression analysis also highlighted TNSF-15. The in vivo rat model of meniscus injury found TNSF-15 to be an essential molecule for meniscus regeneration via SyMSC administration. This molecule and previously reported MoA molecules allowed an MoA-dependent approach to define the mechanism of action for SyMSCs. Therefore, SyMSCs for meniscus regeneration were defined by means of two approaches: the method to separate them from other MSCs and the identification of the MoA molecules. These approaches would be useful for the QC of cell therapy products. Full article
(This article belongs to the Special Issue Latest Research on Mesenchymal Stem Cells)
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18 pages, 1702 KiB  
Article
Repeated Infusions of Bone-Marrow-Derived Mesenchymal Stem Cells over 8 Weeks for Steroid-Refractory Chronic Graft-versus-Host Disease: A Prospective, Phase I/II Clinical Study
by Nayoun Kim, Gi-June Min, Keon-Il Im, Young-Sun Nam, Yunejin Song, Jun-Seok Lee, Eun-Jee Oh, Nack-Gyun Chung, Young-Woo Jeon, Jong Wook Lee and Seok-Goo Cho
Int. J. Mol. Sci. 2024, 25(12), 6731; https://doi.org/10.3390/ijms25126731 - 19 Jun 2024
Cited by 2 | Viewed by 1770
Abstract
Chronic graft-versus-host disease (cGVHD) is a long-term complication of allogeneic hematopoietic stem cell transplantation associated with poor quality of life and increased morbidity and mortality. Currently, there are several approved treatments for patients who do not respond to steroids, such as ruxolitinib. Nevertheless, [...] Read more.
Chronic graft-versus-host disease (cGVHD) is a long-term complication of allogeneic hematopoietic stem cell transplantation associated with poor quality of life and increased morbidity and mortality. Currently, there are several approved treatments for patients who do not respond to steroids, such as ruxolitinib. Nevertheless, a significant proportion of patients fail second-line treatment, indicating the need for novel approaches. Mesenchymal stem cells (MSCs) have been considered a potential treatment approach for steroid-refractory cGVHD. To evaluate the safety and efficacy of repeated infusions of MSCs, we administered intravenous MSCs every two weeks to ten patients with severe steroid-refractory cGVHD in a prospective phase I clinical trial. Each patient received a total of four doses, with each dose containing 1 × 106 cells/kg body weight from the same donor and same passage. Patients were assessed for their response to treatment using the 2014 National Institutes of Health (NIH) response criteria during each visit. Ten patients with diverse organ involvement were enrolled, collectively undergoing 40 infusions as planned. Remarkably, the MSC infusions were well tolerated without severe adverse events. Eight weeks after the initial MSC infusion, all ten patients showed partial responses characterized by the amelioration of clinical symptoms and enhancement of their quality of life. The overall response rate was 60%, with a complete response rate of 20% and a partial response (PR) rate of 40% at the last follow-up. Overall survival was 80%, with a median follow-up of 381 days. Two patients died due to relapse of their primary disease. Immunological analyses revealed a reduction in inflammatory markers, including Suppression of Tumorigenicity 2 (ST2), C-X-C motif chemokine ligand (CXCL)10, and Secreted phosphoprotein 1(SPP1), following the MSC treatment. Repeated MSC infusions proved to be both feasible and safe, and they may be an effective salvage therapy in patients with steroid-refractory cGVHD. Further large-scale clinical studies with long-term follow-up are needed in the future to determine the role of MSCs in cGVHD. Full article
(This article belongs to the Special Issue Latest Research on Mesenchymal Stem Cells)
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Review

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14 pages, 475 KiB  
Review
The Therapeutic Use and Potential of MSCs: Advances in Regenerative Medicine
by Alin Constantin Pînzariu, Roxana Moscalu, Radu Petru Soroceanu, Minela Aida Maranduca, Ilie Cristian Drochioi, Vlad Ionut Vlasceanu, Sergiu Timofeiov, Daniel Vasile Timofte, Bogdan Huzum, Mihaela Moscalu, Dragomir Nicolae Serban and Ionela Lacramioara Serban
Int. J. Mol. Sci. 2025, 26(7), 3084; https://doi.org/10.3390/ijms26073084 - 27 Mar 2025
Viewed by 647
Abstract
Mesenchymal stem cells (MSCs) have emerged as a relevant strategy in regenerative medicine due to their multipotent differentiation capacity, immunomodulatory properties, and therapeutic applications in various medical fields. This review explores the therapeutic use of MSCs, focusing on their role in treating autoimmune [...] Read more.
Mesenchymal stem cells (MSCs) have emerged as a relevant strategy in regenerative medicine due to their multipotent differentiation capacity, immunomodulatory properties, and therapeutic applications in various medical fields. This review explores the therapeutic use of MSCs, focusing on their role in treating autoimmune disorders and neoplastic diseases and in tissue regeneration. We discuss the mechanisms underlying MSC-mediated tissue repair, including their paracrine activity, migration to injury sites, and interaction with the immune system. Advances in cellular therapies such as genome engineering and MSC-derived exosome treatments further enhance their applicability. Key methodologies analyzed include genomic studies, next-generation sequencing (NGS), and bioinformatics approaches to optimize MSC-based interventions. Additionally, we reviewed preclinical and clinical evidence demonstrating the therapeutic potential of MSCs in conditions such as graft-versus-host disease, osteoarthritis, liver cirrhosis, and neurodegenerative disorders. While promising, challenges remain regarding standardization, long-term safety, and potential tumorigenic risks associated with MSC therapy. Future research should focus on refining MSC-based treatments to enhance efficacy and minimize risks. This review underscores the need for large-scale clinical trials to validate MSC-based interventions and fully harness their therapeutic potential. Full article
(This article belongs to the Special Issue Latest Research on Mesenchymal Stem Cells)
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23 pages, 1560 KiB  
Review
Mesenchymal Stromal Cell-Based Products: Challenges and Clinical Therapeutic Options
by Debora B. Mello, Fernanda Cristina Paccola Mesquita, Danúbia Silva dos Santos, Karina Dutra Asensi, Marlon Lemos Dias, Antonio Carlos Campos de Carvalho, Regina Coeli dos Santos Goldenberg and Tais Hanae Kasai-Brunswick
Int. J. Mol. Sci. 2024, 25(11), 6063; https://doi.org/10.3390/ijms25116063 - 31 May 2024
Cited by 6 | Viewed by 2707
Abstract
Mesenchymal stromal cell (MSC)-based advanced therapy medicinal products (ATMPs) are being tried in a vast range of clinical applications. These cells can be isolated from different donor tissues by using several methods, or they can even be derived from induced pluripotent stem cells [...] Read more.
Mesenchymal stromal cell (MSC)-based advanced therapy medicinal products (ATMPs) are being tried in a vast range of clinical applications. These cells can be isolated from different donor tissues by using several methods, or they can even be derived from induced pluripotent stem cells or embryonic stem cells. However, ATMP heterogeneity may impact product identity and potency, and, consequently, clinical trial outcomes. In this review, we discuss these topics and the need to establish minimal criteria regarding the manufacturing of MSCs so that these innovative therapeutics may be better positioned to contribute to the advancement of regenerative medicine. Full article
(This article belongs to the Special Issue Latest Research on Mesenchymal Stem Cells)
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