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Second Edition of Mesenchymal Stem Cells: Intrinsic/Extrinsic Factors Regulating Stemness,...
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Second Edition of Mesenchymal Stem Cells: Intrinsic/Extrinsic Factors Regulating Stemness, Growth, and Differentiation

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

Deadline for manuscript submissions: closed (31 October 2024) | Viewed by 5018

Special Issue Editors

Dr. Federica Facchin

E-Mail Website
Guest Editor
Unit of Histology, Embryology and Applied Biology, Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Via Belmeloro 8, 40126 Bologna, BO, Italy
Interests: human mesenchymal stem cells; cell senescence; cell biology; cell differentiation
Special Issues, Collections and Topics in MDPI journals
Dr. Francesco Alviano

E-Mail Website
Guest Editor
Unit of Histology, Embryology and Applied Biology, Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, Via Belmeloro 8, 40126 Bologna, Italy
Interests: perinatal stem cells; mesenchymal stromal cells; stem cells; membrane lipidomics; cell differentiation; immunomodulation; 3D cell culture systems

Special Issue Information

Dear Colleagues,

This is the expanded second edition of Mesenchymal Stem Cells: Intrinsic/Extrinsic Factors Regulating Stemness, Growth, and Differentiation (https://www.mdpi.com/journal/cells/special_issues/Mesenchymal_Stem_Cells_Stemness_Growth_ Differentiation) that 1st edition has published 6 papers.

Mesenchymal stem/stromal cells (MSCs) are adult stem cells with the capability of self-renewal and multilineage differentiation into skeletal and/or mesodermal tissues, including bone, fat, cartilage, and muscle tissues. Bone marrow has been the primary site for obtaining MSCs, but recent studies have indicated that MSCs are also present at other tissue sites, including adipose, muscle, skin, liver, umbilical cord, tonsil, and blood tissue, and even in urine samples, all of which play a role in regenerating damaged tissues or regulating inflammation or other undiscovered functions. Since the discovery of MSC-like cells 50 years ago, many studies have been carried out to outline their characteristics and investigate their potential therapeutic implications in regenerative medicine and immunomodulation. However, only a few have successfully managed to reach clinical availability, implying that we probably do not yet have a full understanding of the biology of MSCs.

For this Special Issue, we invite authors/experts to submit high-quality original research articles that further expand our knowledge of and provide us with insights into MSCs. We are particularly interested in studies illustrating intrinsic/extrinsic cellular and molecular factors regulating stemness, growth, and differentiation of tissue-specific MSCs as well as their potential implications for tissue engineering and regenerative medicine.

Dr. Federica Facchin
Dr. Francesco Alviano
Guest Editors

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

  • tissue-specific mesenchymal stem cells
  • factors
  • stemness
  • growth
  • differentiation
  • tissue engineering
  • regenerative medicine

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Published Papers (3 papers)

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Research

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15 pages, 2991 KiB  
Article
Elevated IL-6 Expression in Autologous Adipose-Derived Stem Cells Regulates RANKL Mediated Inflammation in Osteoarthritis
by Hyun-Joo Lee, Dae-Yong Kim, Hyeon jeong Noh, Song Yi Lee, Ji Ae Yoo, Samuel Jaeyoon Won, Yoon Sang Jeon, Ji Hoon Baek and Dong Jin Ryu
Cells 2024, 13(24), 2046; https://doi.org/10.3390/cells13242046 - 11 Dec 2024
Viewed by 362
Abstract
Interleukin-6 (IL-6) expression in mesenchymal stem cells (MSCs) has been shown to play a pivotal role in modulating cartilage regeneration and immune responses, particularly in the context of diseases that involve both degenerative processes and inflammation, such as osteoarthritis (OA). However, the precise [...] Read more.
Interleukin-6 (IL-6) expression in mesenchymal stem cells (MSCs) has been shown to play a pivotal role in modulating cartilage regeneration and immune responses, particularly in the context of diseases that involve both degenerative processes and inflammation, such as osteoarthritis (OA). However, the precise mechanism through which IL-6 and other immune-regulatory factors influence the therapeutic efficacy of autologous adipose-derived stem cells (ASCs) transplantation in OA treatment remains to be fully elucidated. This study aims to investigate the relationship between IL-6 expression in autologous ASCs isolated from OA patients and their impact on immune modulation, particularly focusing on the regulation of Receptor Activator of Nuclear factor Kappa-Β Ligand (RANKL), a key mediator of immune-driven cartilage degradation in OA. Autologous ASCs were isolated from the stromal vascular fraction (SVF) of adipose tissue obtained from 22 OA patients. The isolated ASCs were cultured and characterized using reverse transcription polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and flow cytometry to the phenotype and immune regulatory factors of MSCs. Based on IL-6 expression levels, ASCs were divided into high and low IL-6 expression groups. These groups were then co-cultured with activated peripheral blood mononuclear cells (PBMCs) to evaluate their immune-modulatory capacity, including the induction of regulatory T cells, inhibition of immune cell proliferation, and regulation of key cytokines, such as interferon-gamma (IFN-γ). Additionally, RANKL expression, a critical factor in osteoclastogenesis and cartilage degradation, was assessed in both ASC groups. High IL-6-expressing ASCs demonstrated a significantly greater capacity to inhibit immune cell proliferation and IFN-γ production compared to their low IL-6-expressing counterparts under co-culture conditions. Moreover, the group of ASCs with high IL-6 expression showed a marked reduction in RANKL expression, suggesting enhanced potential to control osteoclast activity and subsequent cartilage defect in OA. Conclusion: Autologous ASCs with elevated IL-6 expression exhibit enhanced immunomodulatory properties, particularly in regulating over-activated immune response and reducing osteoclastogenesis through RANKL suppression. These findings indicate that selecting ASCs based on IL-6 expression could enhance the therapeutic efficacy of ASC-based treatments for OA by mitigating immune-driven joint inflammation and cartilage degradation, potentially slowing disease progression. Full article
(This article belongs to the Special Issue Second Edition of Mesenchymal Stem Cells: Intrinsic/Extrinsic Factors Regulating Stemness, Growth, and Differentiation)
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14 pages, 4721 KiB  
Article
Unveiling the Osteogenic Potential of Tetracyclines: A Comparative Study in Human Mesenchymal Stem Cells
by Victor Martin, Ana Francisca Bettencourt, Catarina Santos, Maria Helena Fernandes and Pedro Sousa Gomes
Cells 2023, 12(18), 2244; https://doi.org/10.3390/cells12182244 - 10 Sep 2023
Cited by 4 | Viewed by 2040
Abstract
Tetracyclines (TCs) are a class of broad-spectrum antibiotics with diverse pharmacotherapeutic properties due to their various functional groups being attached to a common core structure. Beyond their antibacterial activity, TCs trigger pleiotropic effects on eukaryotic cells, including anti-inflammatory and potentially osteogenic capabilities. Consequently, [...] Read more.
Tetracyclines (TCs) are a class of broad-spectrum antibiotics with diverse pharmacotherapeutic properties due to their various functional groups being attached to a common core structure. Beyond their antibacterial activity, TCs trigger pleiotropic effects on eukaryotic cells, including anti-inflammatory and potentially osteogenic capabilities. Consequently, TCs hold promise for repurposing in various clinical applications, including bone-related conditions. This study presents the first comprehensive comparison of the in vitro osteogenic potential of four TCs—tetracycline, doxycycline, minocycline, and sarecycline, within human mesenchymal stem cells. Cultures were characterized for metabolic activity, cell morphology and cytoskeleton organization, osteogenic gene expression, alkaline phosphatase (ALP) activity, and the activation of relevant signaling pathways. TCs stimulated actin remodeling processes, inducing morphological shifts consistent with osteogenic differentiation. Osteogenic gene expression and ALP activity supported the osteoinduction by TCs, demonstrating significant increases in ALP levels and the upregulation of RUNX2, SP7, and SPARC genes. Minocycline and sarecycline exhibited the most potent osteogenic induction, comparable to conventional osteogenic inducers. Signaling pathway analysis revealed that tetracycline and doxycycline activate the Wnt pathway, while minocycline and sarecycline upregulated Hedgehog signaling. Overall, the present findings suggest that TCs promote osteogenic differentiation through distinct pathways, making them promising candidates for targeted therapy in specific bone-related disorders. Full article
(This article belongs to the Special Issue Second Edition of Mesenchymal Stem Cells: Intrinsic/Extrinsic Factors Regulating Stemness, Growth, and Differentiation)
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Review

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23 pages, 1705 KiB  
Review
Cytochalasins as Modulators of Stem Cell Differentiation
by Luca Pampanella, Giovannamaria Petrocelli, Provvidenza Maria Abruzzo, Cinzia Zucchini, Silvia Canaider, Carlo Ventura and Federica Facchin
Cells 2024, 13(5), 400; https://doi.org/10.3390/cells13050400 - 25 Feb 2024
Viewed by 1858
Abstract
Regenerative medicine aims to identify new research strategies for the repair and restoration of tissues damaged by pathological or accidental events. Mesenchymal stem cells (MSCs) play a key role in regenerative medicine approaches due to their specific properties, such as the high rate [...] Read more.
Regenerative medicine aims to identify new research strategies for the repair and restoration of tissues damaged by pathological or accidental events. Mesenchymal stem cells (MSCs) play a key role in regenerative medicine approaches due to their specific properties, such as the high rate of proliferation, the ability to differentiate into several cell lineages, the immunomodulatory potential, and their easy isolation with minimal ethical issues. One of the main goals of regenerative medicine is to modulate, both in vitro and in vivo, the differentiation potential of MSCs to improve their use in the repair of damaged tissues. Over the years, much evidence has been collected about the ability of cytochalasins, a large family of 60 metabolites isolated mainly from fungi, to modulate multiple properties of stem cells (SCs), such as proliferation, migration, and differentiation, by altering the organization of the cyto- and the nucleo-skeleton. In this review, we discussed the ability of two different cytochalasins, cytochalasins D and B, to influence specific SC differentiation programs modulated by several agents (chemical or physical) or intra- and extra-cellular factors, with particular attention to human MSCs (hMSCs). Full article
(This article belongs to the Special Issue Second Edition of Mesenchymal Stem Cells: Intrinsic/Extrinsic Factors Regulating Stemness, Growth, and Differentiation)
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