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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 December 2024 | Viewed by 1351

Special Issue Editor


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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

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Keywords

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

Published Papers (2 papers)

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Research

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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
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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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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
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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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