Mesenchymal Stem Cells in Cell Therapy, Regenerative Medicine, and Tissue Engineering

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

Deadline for manuscript submissions: 20 August 2026 | Viewed by 1708

Editors

Department of Transplantation, Faculty of Medicine, Institute of Pediatrics, Jagiellonian University Medical College, 30-663 Krakow, Poland
Interests: mesenchymal stem cells (MSCs); induced pluripotent stem cells (iPSCs); cancer stem cells (CSCs); cardiomyocytes; myogenesis; regenerative medicine; transcriptional analysis; tissue engineering; cell differentiation

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Guest Editor
Department of Biology, University of Mary Hardin-Baylor, 900 College Street, Box 8432, Belton, TX 76513, USA
Interests: microbiology; immunology; regenerative medicine; genetics; stem cells; 3D stem cell culture
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Special Issue Information

Dear Colleagues,

Mesenchymal stem cells (MSCs) have emerged as a key driver in modern therapy due to their remarkable self-renewal capacity, multilineage differentiation potential, and potent immunomodulatory properties. With advancements being made in the field, the synergy between MSCs and tissue engineering is opening new frontiers for treating previously incurable diseases and injuries.

This Special Issue, "Mesenchymal Stem Cells in Cell Therapy, Regenerative Medicine, and Tissue Engineering", aims to provide a comprehensive platform for the latest breakthroughs in MSC research. We seek original research articles and comprehensive reviews that explore the multifaceted roles of MSCs from fundamental molecular mechanisms and secretome analysis to advanced bioengineering approaches involving innovative scaffolds and 3D bioprinting.

Furthermore, we welcome contributions focusing on the clinical translation of MSC-based products and their application in cell therapy across various medical fields. By bridging the gap between basic laboratory findings and therapeutic applications, this Special Issue seeks to highlight current challenges and future perspectives of MSCs in restoring physiological functions and regenerating damaged tissues. We look forward to receiving your contributions to this exciting and rapidly advancing field. Manuscripts providing original research data are particularly welcome.

Dr. Marta Kot
Prof. Dr. Joni H. Ylostalo
Guest Editors

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Keywords

  • mesenchymal stem cells (MSCs)
  • tissue engineering and scaffolds
  • regenerative medicine
  • cell-based therapies
  • differentiation and immunomodulation

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Published Papers (3 papers)

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Research

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25 pages, 5611 KB  
Article
Chemically Defined Medium Enables GDNF-Driven Early Neuronal-like Phenotype of Human Dental Pulp Stem Cells
by Maria-del-Carmen Silva-Lucero, Gustavo Lopez-Toledo, Víctor-Adrián Cortés-Morales, Juan-José Montesinos, Raúl Sampieri-Cabrera, David-E. García, Juan-Ramon Padilla-Mendoza, Obed-Ricardo Lora-Marin, Jesus-Adrian Buendia-Meraz, Fausto-Alejandro Jiménez-Orozco, Israel López-Reyes, Paul Mondragon-Teran and Maria-del-Carmen Cardenas-Aguayo
Cells 2026, 15(10), 953; https://doi.org/10.3390/cells15100953 - 21 May 2026
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Abstract
Background: Human dental pulp stem cells (hDPSCs) are a promising source of multipotent mesenchymal stem cells (MSCs) for regenerative neurology because of their inherent neurogenic potential. However, robust and reproducible protocols for driving their terminal neuronal maturation in a fully defined, xeno-free environment [...] Read more.
Background: Human dental pulp stem cells (hDPSCs) are a promising source of multipotent mesenchymal stem cells (MSCs) for regenerative neurology because of their inherent neurogenic potential. However, robust and reproducible protocols for driving their terminal neuronal maturation in a fully defined, xeno-free environment are lacking. Methods: hDPSCs were isolated from a donor tooth and characterized for mesenchymal (CD105, CD90, CD73, CD13) and stemness-associated markers (SOX2, Oct3/4 and Nanog). Cells were differentiated in a novel, fully chemically defined medium 1% ITS medium (ITS: Insulin, Transferrin, Selenium) supplemented with glial cell line-derived neurotrophic factor (GDNF) or brain-derived neurotrophic factor (BDNF). Neuronal commitment and partial maturation were assessed via immunofluorescence, Western blot, and RT-PCR for markers such as NeuN (Neuronal nuclei) and NF-M (Neurofilament medium chain), and functionally by whole-cell patch-clamp electrophysiology. Results: Although undifferentiated hDPSCs expressed neural progenitor markers (βIII-tubulin and Nestin), only GDNF treatment in a chemically defined medium significantly upregulated mature neuronal markers (NeuN and NF-M) and downregulated mesenchymal markers. Importantly, GDNF-treated cells exhibited key functional changes, including hyperpolarized resting membrane potentials, increased membrane capacitance, and elevated input resistance, which are electrophysiological hallmarks of neural precursor or early neuronal maturation, compared to control cells cultured in medium containing fetal bovine serum (FBS). Although action potentials were not elicited, this represents a significant advancement toward achieving a functional neuronal state. Conclusion: This study demonstrates that a fully chemically defined medium enables GDNF to drive hDPSCs beyond the neural progenitor state towards a partially mature neuronal phenotype. This defined medium protocol eliminates serum variability, enhances reproducibility, and provides a critical step towards standardizing hDPSC-derived neuronal cells for disease modeling and cell-based therapy. Full article
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18 pages, 2579 KB  
Article
Voltage-Gated Sodium Channels Regulate the Migration Potential of Human Endometrial Mesenchymal Stem/Stromal Cells in 2D and 3D Culture
by Margarita Shamatova, Mariia Shorokhova, Irina Vassilieva, Vladislav Chubinskiy-Nadezhdin and Anastasia Sudarikova
Cells 2026, 15(10), 851; https://doi.org/10.3390/cells15100851 - 7 May 2026
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Abstract
Human endometrial mesenchymal stem/stromal cells (eMSCs) are widely used in laboratories and clinical applications to study various aspects of tissue engineering and regenerative medicine. Three-dimensional (3D) cultivated MSCs have a higher therapeutic efficacy compared to 2D culture. Ion channels are involved in maintaining [...] Read more.
Human endometrial mesenchymal stem/stromal cells (eMSCs) are widely used in laboratories and clinical applications to study various aspects of tissue engineering and regenerative medicine. Three-dimensional (3D) cultivated MSCs have a higher therapeutic efficacy compared to 2D culture. Ion channels are involved in maintaining many physiological cell functions, including proliferation, differentiation, apoptosis, and migration. This study describes the functional expression of voltage-gated sodium channels (NaV) in eMSCs and the role of these channels in cell migration. Using RT-PCR analysis and immunofluorescent microscopy, we identified the expression of almost all pore-forming alpha (NaV 1.1, 1.2, 1.4–1.9) and channel-modulating beta-NaV subunits (except beta2) in eMSCs. In the whole-cell patch-clamp configuration, channels activated by membrane depolarization of eMSC were detected. The channels were blocked by the selective NaV antagonist TTX in nanomolar concentrations. The NaV agonist veratridine at a concentration of less than 40 μM inhibited voltage-gated sodium currents, while 100 μM and above prevented channel inactivation. The wound healing assay showed that both TTX (10 μM) and veratridine (100 μM) reduced the migration properties (the wound healing rate) of eMSCs cultivated in 2D conditions compared to the control. An opposite effect by both agents was shown on the motility of eMSCs cultivated in 3D conditions, increasing the cell spreading rate from spheroids. Our data suggest that NaV channels are expressed in human eMSCs and play an important role in the regulation of stem cell migration; this regulatory mechanism significantly depends on the culture conditions of MSCs. Full article
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Review

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18 pages, 646 KB  
Review
Genetically Modified MSCs for Targeted Regeneration: Balancing Efficacy, Biosafety, and GMP Standardization
by Kristina V. Kitaeva, Ivan Y. Filin, Albert A. Rizvanov, Shahlo Turdikulova, Mirakbar Yakubov, Oksana Charishnikova and Valeriya V. Solovyeva
Cells 2026, 15(15), 1406; https://doi.org/10.3390/cells15151406 - 3 Aug 2026
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Abstract
Mesenchymal stromal cells (MSCs) are a versatile platform for regenerative medicine and gene delivery because they combine multipotency, immunoregulatory activity, and injury-directed trafficking. Translation is nevertheless limited by donor- and tissue-dependent heterogeneity, variable biodistribution, and engineering-related risks. This review evaluates genetically modified MSCs [...] Read more.
Mesenchymal stromal cells (MSCs) are a versatile platform for regenerative medicine and gene delivery because they combine multipotency, immunoregulatory activity, and injury-directed trafficking. Translation is nevertheless limited by donor- and tissue-dependent heterogeneity, variable biodistribution, and engineering-related risks. This review evaluates genetically modified MSCs as medicinal products rather than as a general MSC class. We compare self-inactivating lentiviral (SIN-LV) transduction, which provides efficient and durable expression and has limited early clinical experience, with targeted genome editing, which can define the integration locus and copy number but remains constrained by variable precise knock-in efficiency, off-target and double-strand-break-associated effects, manufacturing cost, and the absence of long-term clinical safety data. We integrate preclinical and clinical evidence with GMP-compatible manufacturing, potency testing, genomic surveillance, and release criteria. Particular attention is given to safe-harbor integration and B2M/CIITA-based hypoimmunogenic designs as strategies to reduce engineering-related batch variability and HLA-dependent donor variability. Together, these developments support a transition from empirically optimized MSC preparations toward molecularly defined cellular medicines with predefined genotype, expression, potency, and safety attributes. Full article
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