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Cells
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Modulation of Senescence and Differentiation in Human Mesenchymal Stem Cells
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Modulation of Senescence and Differentiation in Human Mesenchymal Stem Cells

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

Deadline for manuscript submissions: 1 September 2026 | Viewed by 4955

Special Issue Editors

Dr. Federica Facchin

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Guest Editor
Department of Medical and Surgical Sciences (DIMEC), Unit of Histology, Embryology and Applied Biology, University of Bologna, Via Belmeloro 8, 40126 Bologna, Italy
Interests: human mesenchymal stem cells; cell senescence; cell biology; cell differentiation
Special Issues, Collections and Topics in MDPI journals
Dr. Silvia Canaider

E-Mail Website
Guest Editor
Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Unit of Histology, Embryology and Applied Biology, University of Bologna, Via Belmeloro 8, 40126 Bologna, BO, Italy
Interests: human mesenchymal stem cells; cell senescence; cell biology; cell differentiation; use of chemical (natural or synthetic molecules) od physical stimuli to modulate the stemness, the proliferation, differentiation and senescence of human stem cells from adult and perinatal tissues; the relationship between cytoskeleton alteration and morpho-functional properties of human stem cells from adult and perinatal tissues; strategies to induce cardiomyocytes to re-enter the cell cycle; gender differences in transcriptome and cell senescence in human stem cells; theoretic biology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Mesenchymal stem/stromal cells (MSCs) are adult stem cells used in regenerative medicine to treat various pathologies due to their self-renewal ability and multilineage differentiation. However, MSCs undergo cellular senescence during their in vitro expansion, and they may become senescent in vivo due to the influence of multiple molecular, cellular, and environmental interactions. Many studies have been carried out to investigate the biological properties of MSCs and the possibility of modulating their behaviour pre- and post-transplantation. 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 deepening our understanding of senescence and differentiation in tissue-specific MSCs, as well as those exploring the modulation of these processes through natural and synthetic molecules with the aim of improving MSC potential in tissue engineering and regenerative medicine.

Dr. Federica Facchin
Dr. Silvia Canaider
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 250 words) can be sent to the Editorial Office for assessment.

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
  • cell senescence
  • cell differentiation
  • natural and synthetic molecules
  • tissue engineering
  • regenerative medicine

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Published Papers (3 papers)

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Research

24 pages, 9054 KB  
Article
Toward Efficient Beige Adipogenesis: Protocol Optimization Using Adipose-Derived Stem Cells
by Klaudia Simka-Lampa, Agnieszka Kosowska, Wojciech Garczorz, Małgorzata Kimsa-Furdzik, Grzegorz Wystrychowski, Celina Kruszniewska-Rajs, Małgorzata Muc-Wierzgoń and Tomasz Francuz
Cells 2026, 15(1), 54; https://doi.org/10.3390/cells15010054 - 28 Dec 2025
Viewed by 931
Abstract
Brown adipose tissue (BAT) has emerged as a promising therapeutic target for metabolic disorders such as type 2 diabetes and obesity. To advance research on BAT activation and elucidate the mechanisms underlying adipogenesis, it is crucial to develop a reliable in vitro model. [...] Read more.
Brown adipose tissue (BAT) has emerged as a promising therapeutic target for metabolic disorders such as type 2 diabetes and obesity. To advance research on BAT activation and elucidate the mechanisms underlying adipogenesis, it is crucial to develop a reliable in vitro model. This study aimed to optimize the differentiation of adipose-derived stem cells (ADSCs) into beige adipocytes and to validate the protocol using primary human ADSCs obtained from eight donors. Protocol optimization was first performed with commercial ADSCs, testing more than 30 combinations of adipogenic conditions. Differentiation was assessed by microscopy, Oil Red O staining, and uncoupling protein 1 (UCP1) expression via reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot. Among the key adipogenic factors, rosiglitazone proved more effective than indomethacin. Extending the induction phase from 4 to 8 days and maintaining dexamethasone throughout the culture markedly enhanced differentiation efficiency. Serum concentration above 5% was inhibitory, while optimal conditions were identified as 5 μM rosiglitazone and 20 μg/mL insulin. The optimized protocol successfully induced beige adipogenesis in ADSCs from eight independent donors, though efficiency varied considerably which could be attributed to individual donor variability. These findings provide a robust in vitro model for studying beige fat biology and highlight the relevance of personalized approaches in metabolic research. Full article
(This article belongs to the Special Issue Modulation of Senescence and Differentiation in Human Mesenchymal Stem Cells)
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17 pages, 1631 KB  
Article
Functionally Distinct Shed Subpopulations Detected After Magnetic-Activated Cell Sorting of CD71 and CD146
by Marina Miteva, Emilia Karova, Natalia Grancharova, Mirela Marinova-Takorova, Violeta Dogandzhiyska, Krasimir Hristov, Nikolay Ishkitiev, Vanyo Mitev, Evgeniy Aleksiev and Zornitsa Mihaylova
Cells 2025, 14(24), 2010; https://doi.org/10.3390/cells14242010 - 17 Dec 2025
Cited by 1 | Viewed by 568
Abstract
Mesenchymal stem cells derived from human exfoliated deciduous teeth (SHED) are a promising source for regenerative therapies due to their multipotency, proliferative capacity, and immunomodulatory properties. The present study aimed to isolate and characterize SHED subpopulations based on CD71 and CD146 expression and [...] Read more.
Mesenchymal stem cells derived from human exfoliated deciduous teeth (SHED) are a promising source for regenerative therapies due to their multipotency, proliferative capacity, and immunomodulatory properties. The present study aimed to isolate and characterize SHED subpopulations based on CD71 and CD146 expression and evaluate their multilineage differentiation potential. SHED were obtained from pediatric donors and separated into CD71+, CD71−, CD146+, and CD146− fractions using magnetic-activated cell sorting (MACS). CD71+/CD71− and CD146+/CD146− populations were isolated independently; no simultaneous double sorting for both markers was performed. Immunocytochemistry was employed to confirm the expression of surface and intracellular markers, including STRO-1, CD44, nestin, and vimentin. Multilineage differentiation assays toward osteogenic, adipogenic, and chondrogenic lineages revealed that CD71+ cells exhibited reduced osteogenic capacity compared to CD71− cells, whereas CD146+ cells showed enhanced osteogenic and adipogenic differentiation. Chondrogenic differentiation seemed unaffected by marker expression under the 2D conditions employed. These results highlight functional heterogeneity within SHED populations and indicate that CD71 and CD146 independently influence differentiation outcomes. The selective enrichment of CD146+ SHED may enhance osteogenic and adipogenic regenerative applications, while CD71+ subsets may serve as a valuable model for studying proliferation and paracrine effects. Limitations include the use of in vitro differentiation assays and the absence of in vivo validation; additionally, combined CD71/CD146 analysis may further clarify the relationship between metabolic activity and stem/progenitor niche characteristics. Overall, marker-based characterization of SHED subpopulations provides insight into their biological properties and potential utility in targeted cell-based therapeutic strategies. Full article
(This article belongs to the Special Issue Modulation of Senescence and Differentiation in Human Mesenchymal Stem Cells)
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27 pages, 7998 KB  
Article
Tert-Butyl Hydroperoxide in Human Adult Mesenchymal Stem Cells Isolated from Dermis: A Stress-Induced Premature Senescence Model
by Luca Pampanella, Giovannamaria Petrocelli, Provvidenza Maria Abruzzo, Riccardo Tassinari, Beatrice Bassoli, Rossella Sgarzani, Margherita Maioli, Carlo Ventura, Silvia Canaider and Federica Facchin
Cells 2025, 14(19), 1563; https://doi.org/10.3390/cells14191563 - 8 Oct 2025
Cited by 1 | Viewed by 1512
Abstract
Stem cell (SC)-based therapy exploits the ability of cells to migrate to damaged tissues and repair them. In this context, there is a strong interest in the use of mesenchymal stem cells (MSCs), multipotent SCs that are easy to obtain and are able [...] Read more.
Stem cell (SC)-based therapy exploits the ability of cells to migrate to damaged tissues and repair them. In this context, there is a strong interest in the use of mesenchymal stem cells (MSCs), multipotent SCs that are easy to obtain and are able to differentiate into various cell lineages. However, MSCs undergo cellular senescence during in vitro expansion, and may also become senescent in vivo, influenced by multiple molecular, cellular, and environmental interactions. Therefore, the development of in vitro cell models is crucial to study the mechanisms underlying senescence in MSCs. This study aimed to investigate the effects of tert-butyl hydroperoxide (t-BHP) as a senescence inducer in human dermal MSCs (hDMSCs), a promising tool for tissue repair. t-BHP induced a pro-senescent effect on hDMSCs greater than hydrogen peroxide (H2O2), as evidenced by ROS production, DNA damage, cell cycle arrest, inhibition of cell proliferation, changes in cellular and nuclear morphology, and cytoskeletal reorganization, as well as the increase in other senescence markers, including senescence-associated β-galactosidase (SA-β-Gal)-positive cells, and senescence-associated secretory phenotype (SASP). These results indicate that t-BHP could be a promising compound for inducing stress-induced premature senescence (SIPS) in hDMSCs, providing a valuable tool to investigate this process and evaluate the efficacy of senolytic compounds. Full article
(This article belongs to the Special Issue Modulation of Senescence and Differentiation in Human Mesenchymal Stem Cells)
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