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IJMS
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Mesenchymal Stem Cells Differentiation in Health and Disease
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Mesenchymal Stem Cells Differentiation in Health and Disease

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 20 January 2025 | Viewed by 8138

Special Issue Editor

Dr. Emanuela Chiarella

E-Mail Website
Guest Editor
Department of Experimental and Clinical Medicine, University “Magna Græcia”, 88100 Catanzaro, Italy
Interests: mesenchymal stem cells; adipogenic differentiation; osteoblastic differentiation; chondrogenic differentiation; haematopoietic stem cells; cell metabolism
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues, 

Mesenchyme is a loosely organized embryonic connective tissue of undifferentiated cells, predominantly originating from the embryonic mesoderm, although it may also be derived from the neural crest, an ectodermal cell population, via an epithelial-to-mesenchymal transition (EMT). Mesenchyme is composed morphologically through a prominent extracellular matrix containing a loose aggregate of reticular fibrils and unspecialized mesenchymal stem cells. Unlike epithelial cells, organized into closely adherent sheets, mesenchymal cells can migrate easily, sustaining a connective tissue production during embryogenesis. In recent decades, a role has been recognized for the migration ability of mesenchymal stem cells in tumor-targeted delivery vehicles and tumor-related stroma formation. Mesenchymal stem cells (MSCs) are multipotent stromal cells able to self-renew and differentiate into many different types of cells, including bone, cartilage, muscle, fat cells and connective tissue. They can be isolated from a variety of tissues, such as bone marrow, adipose tissue, the placenta, cord blood and polyps. MSCs are characterized by the expression of CD73, CD90 and CD105 cell markers and are negative for hematopoietic and endothelial markers (CD14, CD11b, CD19, CD79, CD34, CD45 and HLA-DR). make These cells have been found to be a good source for experimental practice due to their ease of harvest and quantity obtained; indeed, they emerged in the past two decades as promising candidates for clinical applications, especially in cell replacement therapies for mesenchymal tissues such as bone and cartilage. The dysregulation of the MSC differentiation process occurs frequently in many bone diseases, for example, osteogenesis imperfecta or sarcoma. Investigating the molecular basis involved in regulating the differentiation and maturation of MSCs into osteoblastic cells or chondrocytes in health and disease conditions is essential for the development of innovative approaches for therapy. This Special Issue of IJMS provides an opportunity for the description of recent original research advancements in the field of MSCs, focusing on transcriptional factors involved in osteoblastic differentiation. We are particularly interested in the analysis of a range of transcription factors with regulatory roles at different stages during the osteoblastic differentiation of MSCs in order to gain an understanding of bone development in health and disease.

Dr. Emanuela Chiarella
Guest Editor

Manuscript Submission Information

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Keywords

  • mesoderm
  • mesenchymal stem cells
  • osteogenic differentiation
  • chondrogenic differentiation
  • adipogenic differentiation
  • MSC clinical applications

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Published Papers (3 papers)

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Research

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17 pages, 2608 KiB  
Article
Unveiling Polysomal Long Non-Coding RNA Expression on the First Day of Adipogenesis and Osteogenesis in Human Adipose-Derived Stem Cells
by Bernardo Bonilauri, Annanda Lyra Ribeiro, Lucía Spangenberg and Bruno Dallagiovanna
Int. J. Mol. Sci. 2024, 25(4), 2013; https://doi.org/10.3390/ijms25042013 - 7 Feb 2024
Cited by 1 | Viewed by 1351
Abstract
Understanding the intricate molecular mechanisms governing the fate of human adipose-derived stem cells (hASCs) is essential for elucidating the delicate balance between adipogenic and osteogenic differentiation in both healthy and pathological conditions. Long non-coding RNAs (lncRNAs) have emerged as key regulators involved in [...] Read more.
Understanding the intricate molecular mechanisms governing the fate of human adipose-derived stem cells (hASCs) is essential for elucidating the delicate balance between adipogenic and osteogenic differentiation in both healthy and pathological conditions. Long non-coding RNAs (lncRNAs) have emerged as key regulators involved in lineage commitment and differentiation of stem cells, operating at various levels of gene regulation, including transcriptional, post-transcriptional, and post-translational processes. To gain deeper insights into the role of lncRNAs’ in hASCs’ differentiation, we conducted a comprehensive analysis of the lncRNA transcriptome (RNA-seq) and translatome (polysomal-RNA-seq) during a 24 h period of adipogenesis and osteogenesis. Our findings revealed distinct expression patterns between the transcriptome and translatome during both differentiation processes, highlighting 90 lncRNAs that are exclusively regulated in the polysomal fraction. These findings underscore the significance of investigating lncRNAs associated with ribosomes, considering their unique expression patterns and potential mechanisms of action, such as translational regulation and potential coding capacity for microproteins. Additionally, we identified specific lncRNA gene expression programs associated with adipogenesis and osteogenesis during the early stages of cell differentiation. By shedding light on the expression and potential functions of these polysome-associated lncRNAs, we aim to deepen our understanding of their involvement in the regulation of adipogenic and osteogenic differentiation, ultimately paving the way for novel therapeutic strategies and insights into regenerative medicine. Full article
(This article belongs to the Special Issue Mesenchymal Stem Cells Differentiation in Health and Disease)
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14 pages, 2720 KiB  
Article
Osteogenic Differentiation of Human Periodontal Ligament Stromal Cells Influences Their Immunosuppressive Potential toward Allogenic CD4+ T Cells
by Oliwia Miłek, Dino Tur, Lucia Ahčin, Olha Voitseshyna, Christian Behm and Oleh Andrukhov
Int. J. Mol. Sci. 2023, 24(22), 16439; https://doi.org/10.3390/ijms242216439 - 17 Nov 2023
Cited by 1 | Viewed by 1482
Abstract
The differentiation ability of human periodontal ligament mesenchymal stromal cells (hPDL-MSCs) in vivo is limited; therefore, some studies considered strategies involving their pre-differentiation in vitro. However, it is not known how the differentiation of hPDL-MSCs influences their immunomodulatory properties. This study investigated how [...] Read more.
The differentiation ability of human periodontal ligament mesenchymal stromal cells (hPDL-MSCs) in vivo is limited; therefore, some studies considered strategies involving their pre-differentiation in vitro. However, it is not known how the differentiation of hPDL-MSCs influences their immunomodulatory properties. This study investigated how osteogenic differentiation of hPDL-MSCs affects their ability to suppress CD4+ T-lymphocyte proliferation. hPDL-MSCs were cultured for 21 days in osteogenic differentiation or standard culture media. Allogeneic CD4+ T lymphocytes were co-cultured with undifferentiated and differentiated cells in the presence or absence of interferon (IFN)-γ, interleukin (IL)-1β or tumor necrosis factor (TNF)-α, and their proliferation and apoptosis were measured. Additionally, the effects of these cytokines on the expression of immunomodulatory or pro-inflammatory factors were investigated. Our data show that osteogenic differentiation of hPDL-MSCs reduced their ability to suppress the proliferation of CD4+ T lymphocytes in the presence of IFN-γ and enhanced this ability in the presence of IL-1β. These changes were accompanied by a slightly decreased proportion of apoptotic CD4+ in the presence of IFN-γ. The osteogenic differentiation was accompanied by decreases and increases in the activity of indoleamine-2,3-dioxygenase in the presence of IFN-γ and IL-1β, respectively. The basal production of interleukin-8 by hPDL-MSCs was substantially increased upon osteogenic differentiation. In conclusion, this study suggests that pre-differentiation strategies in vitro may impact the immunomodulatory properties of hPDL-MSCs and subsequently affect their therapeutic effectiveness in vivo. These findings provide important insights for the development of MSC-based therapies. Full article
(This article belongs to the Special Issue Mesenchymal Stem Cells Differentiation in Health and Disease)
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Review

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18 pages, 1102 KiB  
Review
A Review of Novel Strategies for Human Periodontal Ligament Stem Cell Ex Vivo Expansion: Are They an Evidence-Based Promise for Regenerative Periodontal Therapy?
by Anna Di Vito, Jessica Bria, Alessandro Antonelli, Maria Mesuraca, Tullio Barni, Amerigo Giudice and Emanuela Chiarella
Int. J. Mol. Sci. 2023, 24(9), 7798; https://doi.org/10.3390/ijms24097798 - 25 Apr 2023
Cited by 3 | Viewed by 3018
Abstract
Periodontitis is a gingiva disease sustained by microbially associated and host-mediated inflammation that results in the loss of the connective periodontal tissues, including periodontal ligament and alveolar bone. Symptoms include swollen gingiva, tooth loss and, ultimately, ineffective mastication. Clinicians utilize regenerative techniques to [...] Read more.
Periodontitis is a gingiva disease sustained by microbially associated and host-mediated inflammation that results in the loss of the connective periodontal tissues, including periodontal ligament and alveolar bone. Symptoms include swollen gingiva, tooth loss and, ultimately, ineffective mastication. Clinicians utilize regenerative techniques to rebuild and recover damaged periodontal tissues, especially in advanced periodontitis. Human periodontal ligament stem cells (hPDLSCs) are considered an appealing source of stem cells for regenerative therapy in periodontium. hPDLSCs manifest the main properties of mesenchymal stem cells, including the ability to self-renew and to differentiate in mesodermal cells. Significant progress has been made for clinical application of hPDLSCs; nevertheless, some problems remain, including the small number of cells isolated from each sample. In recent decades, hPDLSC ex vivo expansion and differentiation have been improved by modifying cell culture conditions, especially with the supplementation of cytokines’ or growth factors’ mix, chemicals, and natural compounds, or by using the decellularized extracellular matrix. Here, we analyzed the changes in stemness properties and differentiation potential of hPDLSCs when culturing in alternative media. In addition, we focused on the possibility of replacing FBS with human emoderivates to minimize the risks of xenoimmunization or zoonotic transmission when cells are expanded for therapeutic purposes. Full article
(This article belongs to the Special Issue Mesenchymal Stem Cells Differentiation in Health and Disease)
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