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Role and Application of Stem Cells in Regenerative Medicine (Volume 5)

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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 June 2026 | Viewed by 10403

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Special Issue Editors

Prof. Dr. Oriana Trubiani

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Department of Innovative Technologies in Medicine & Dentistry, University “G. d’Annunzio”, Chieti-Pescara, via dei Vestini, 31, 66100 Chieti, Italy
Interests: stem cells; biomaterials; regenerative medicine
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Dr. Francesca Diomede

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Guest Editor

Department of Innovative Technologies in Clinical Medicine & Dentistry, University “G. d’Annunzio” Chieti-Pescara, 66100 Chieti, Italy
Interests: regenerative medicine; stem cells; oral stem cells; biomaterials; extracellular vesicles; exosomes; epithelial–mesenchymal transition
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Dr. Jacopo Pizzicannella

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Guest Editor

Department of Engeneering and Geology, University “G. d’Annunzio” Chieti-Pescara, 66100 Chieti, Italy
Interests: regenerative medicine; stem cells; biomaterials; extracellular vesicles; exosomes; cardiac regeneration; cardiomyocytes
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue is the fifth version of our previous Special Issue "Role and Application of Stem Cells in Regenerative Medicine”.

https://www.mdpi.com/journal/ijms/special_issues/stem_cells_med

https://www.mdpi.com/journal/ijms/special_issues/stem_cells_med2

https://www.mdpi.com/journal/ijms/special_issues/stem_cells_med3

https://www.mdpi.com/journal/ijms/special_issues/59769A8GJ0

Mesenchymal stem cells (MSCs) are currently being used in preclinical and clinical trials for their ability to promote wound healing and tissue regeneration.

In particular, oral-derived mesenchymal stem cells (oral-MSCs) are accessible and can be collected and used in regenerative medicine, avoiding ethical concerns. They can be derived from different oral tissues, such as human exfoliated deciduous teeth (SHED), periodontal ligaments (PDLSCs), dental follicles (as progenitor (P) cells, DFPCs), apical papilla (SCAP), dental pulp (DPSCs), and gingival tissue (GMSCs), and possess multipotential properties and high proliferation and differentiation abilities. Moreover, oral MSCs have paracrine and immunomodulatory capacities, representing an innovative tool for the treatment of various degenerative and traumatic processes, including skeletal and maxilla-facial degeneration, trauma or ischemia injuries, and neurodegenerative and immune disorders.

This new Special Issue will comprise a selection of research papers and reviews contributing to the evaluation of the aptitude of oral-MSCs and their secretome for tissue regeneration, thereby facilitating the fabrication of 3D living constructs for future clinical applications.

Moreover, in vitro and in vivo studies on the molecular mechanisms involved in tissue regeneration are of interest, since they will provide a possibly important contribution to the development of stem-cell-based regeneration strategies and to the identification of key biological regulation processes that remain uncovered.

Prof. Dr. Oriana Trubiani
Dr. Francesca Diomede
Dr. Jacopo Pizzicannella
Guest Editors

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Keywords

mesenchymal stem cells
tissue regeneration
regenerative medicine
immunomodulatory process

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Published Papers (4 papers)

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Research

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37 pages, 5082 KB

Open AccessArticle

Cytoprotective and Immunomodulatory Properties of Mesenchymal Stem Cell Secretome and Its Effect on Organotypic Hippocampal Cultures in Mouse Model of Temporal Lobe Epilepsy

by Martyna Strzelec, Jan Detka, Marta Kot, Qi Wang, Małgorzata K. Sobocińska, Jens D. Mikkelsen and Marcin Majka

Int. J. Mol. Sci. 2026, 27(1), 265; https://doi.org/10.3390/ijms27010265 - 26 Dec 2025

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Abstract

Temporal lobe epilepsy (TLE), the most common form of epilepsy, is often resistant to symptomatic treatment and characterized by persistent neuroinflammation, creating an urgent need for therapeutic strategies that can modulate early disease mechanisms. In this study, we examined the ability of the human MSC-derived secretome to influence epileptic hippocampal tissue during the latent phase of epileptogenesis using an ex vivo model. For this purpose, we characterized the MSC-derived secretome using multiplex Luminex profiling, optimized organotypic hippocampal cultures (OHCs) by evaluating cell viability, validated the pilocarpine-induced TLE model both morphologically and electrophysiologically, and investigated the influence of MSC-conditioned medium (MSC-CM) on epileptic hippocampal tissue. Using mouse-derived OHCs, we found that MSC-CM supports the preservation of nestin- and doublecortin (DCX)-positive progenitor cells, reduces NF-κB (p50/p105) levels, decreases LDH release into the culture medium, and modulates IL-6 secretion during the latent phase of epileptogenesis. Taken together, these findings suggest that the MSC-derived secretome exerts cytoprotective and context-dependent immunomodulatory effects, attenuating inflammatory signaling and cellular stress while supporting the preservation of neural progenitor markers in epileptic tissue. These properties highlight a potential phase-specific therapeutic window to modulate pathological processes during the latent phase of epileptogenesis. Full article

(This article belongs to the Special Issue Role and Application of Stem Cells in Regenerative Medicine (Volume 5))

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26 pages, 10397 KB

Open AccessArticle

Dentinogenic Effect of BMP-7 on Wharton’s Jelly Mesenchymal Stem Cells Cultured in Decellularized Dental Pulp

by Nur Athirah Ahmad Shuhaimi, Dalia Abdullah, Farinawati Yazid, Sook Luan Ng, Nurul Inaas Mahamad Apandi and Nur Azurah Abdul Ghani

Int. J. Mol. Sci. 2025, 26(23), 11760; https://doi.org/10.3390/ijms262311760 - 4 Dec 2025

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Abstract

Decellularized tissue scaffolds mimic the native pulp-dentin microenvironment and support the odontogenic development of stem cells. This study investigated the dentinogenic effect of Wharton’s Jelly Mesenchymal Stem Cells (WJMSCs) in decellularized human dental pulp (DHDP) with bone morphogenic protein-7 (BMP-7) at three concentrations: 0 ng/mL (control), 25 ng/mL, and 50 ng/mL. The effects of BMP-7 were evaluated by histological examination, WJMSC viability using AlamarBlue, dentinogenic gene expression by qPCR, and dentinogenic protein expression by ELISA. By day 21, all three groups exhibited cell distribution along the pore surfaces of DHDP, followed by the presence of a collagen matrix in the tissue. WJMSC viability treated with 25 ng/mL and 50 ng/mL showed a statistically significant increase on days 7, 14, and 21 compared to the control group (p < 0.05). Gene expression analysis of dentin sialophosphoprotein (DSPP) and dentin matrix protein-1 (DMP-1), and odontogenic marker (Runx2) revealed 25 ng/mL BMP-7 resulted in significantly higher expression levels for DMP-1 and Runx2 on day 21 compared to control and 50 ng/mL BMP-7 group (p < 0.05). DSPP and DMP-1 protein expressions also showed trends similar to those of gene expressions. BMP-7 (25 ng/mL) can maintain cell viability and promote dentinogenic effects of WJMSC in the DHDP scaffold. Full article

(This article belongs to the Special Issue Role and Application of Stem Cells in Regenerative Medicine (Volume 5))

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26 pages, 6772 KB

Open AccessArticle

Adaptive and Pathological Changes of the Cardiac Muscle in a Mouse Model of Renocardiac Syndrome: The Role of Nestin-Positive Cells

by Polina A. Abramicheva, Ilya A. Sokolov, Arina A. Druzhinina, Daria M. Potashnikova, Nadezda V. Andrianova, Dmitry S. Semenovich, Vasily N. Manskikh, Ljubava D. Zorova, Elmira I. Yakupova, Ivan M. Vikhlyantsev, Olga S. Tarasova, Dmitry B. Zorov and Egor Y. Plotnikov

Int. J. Mol. Sci. 2025, 26(16), 8100; https://doi.org/10.3390/ijms26168100 - 21 Aug 2025

Viewed by 1462

Abstract

Renocardiac syndrome type 4 (RCS4) is a common comorbid pathology, but the mechanisms of kidney dysfunction-induced cardiac remodeling and the involvement of cardiac progenitor cells (CPCs) in this process remain unclear. The aim of this study was to investigate the structural and functional changes in the cardiac muscle in RCS4 induced by unilateral ureteral obstruction (UUO) and the role of nestin⁺ CPCs in these. Heart function and localization of nestin⁺ cells in the myocardium were assessed using nestin-GFP transgenic mice subjected to UUO for 14 and 28 days. UUO resulted in cardiac hypertrophy, accompanied by an elongation of the QRS wave on the ECG, decreased expression of Cxcl1, Cxcl9, and Il1b, reduced the number of CD11b⁺ cells, and increased in titin isoform parameters, such as T1/MHC and TT/MHC ratios, without changes in fibrosis markers. The number of nestin⁺ cells increased in the myocardium with increased duration of UUO and displayed an SCA-1⁺TBX5⁺ phenotype, consistent with CPCs. Thus, cardiac pathology in RCS4 was manifested by cardiomyocyte hypertrophy with changes in the electrophysiological phenotype of the heart, not accompanied by fibrosis or inflammation. Nestin⁺ cardiac cells retained the CPC phenotype during UUO, and their number increased, which suggests their participation in regenerative processes in the heart. Full article

(This article belongs to the Special Issue Role and Application of Stem Cells in Regenerative Medicine (Volume 5))

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Review

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31 pages, 1705 KB

Open AccessReview

Stem Cells in Regenerative Medicine: A Journey from Adult Stem Cells to Induced Pluripotent Cells

by Ylenia Della Rocca, Antonella Mazzone, Guya Diletta Marconi, Oriana Trubiani, Jacopo Pizzicannella and Francesca Diomede

Int. J. Mol. Sci. 2025, 26(17), 8255; https://doi.org/10.3390/ijms26178255 - 26 Aug 2025

Cited by 1 | Viewed by 7443

Abstract

Regenerative medicine is the branch of medicine that aims to repair and regenerate damaged tissues and presents promising avenues for addressing a wide range of currently incurable diseases. Regenerative medicine is based on the use of cell therapy with stem cells that can differentiate into differentiated cells of specific tissues. There are various types of stem cells, which are different in potential and derivation. The aim of this review is to summarize the types of stem cells most studied and recently discovered, from adult stem cells to innovative induced pluripotent stem cells (iPSCs), for regenerative medicine purposes. The stem cells involved in the identification of new regenerative therapeutic approaches are analyzed here through a classification based on the tissues’ embryonic derivation: stem cells from ectodermal derivation tissues, stem cells from mesodermal derivation tissues, stem cells from endodermal derivation tissues, and iPSCs. Full article

(This article belongs to the Special Issue Role and Application of Stem Cells in Regenerative Medicine (Volume 5))

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