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Role and Application of Stem Cells in Regenerative Medicine 3.0
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Role and Application of Stem Cells in Regenerative Medicine 3.0

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: closed (31 July 2022) | Viewed by 21762

Special Issue Editors

Prof. Dr. Oriana Trubiani

E-Mail Website
Guest Editor
Department of Medical, Oral and Biotechnological Sciences, University “G. d’Annunzio”, Chieti-Pescara, Via dei Vestini, 31, 66100 Chieti, Italy
Interests: stem cells; dentistry; regenerative medicine
Special Issues, Collections and Topics in MDPI journals
Dr. Francesca Diomede

E-Mail Website
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
Special Issues, Collections and Topics in MDPI journals
Dr. Jacopo Pizzicannella

E-Mail Website
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 third 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

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 capacity, 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 as well as immune disorders.

This Special Issue, “Role and Application of Stem Cells in Regenerative Medicine 3.0”, of the International Journal of Molecular Sciences will comprise a selection of research papers and reviews contributing to the evaluation of the aptitude of oral-MSCs in particular and their secretome for tissue regeneration, as a starting point for 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

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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • Mesenchymal stem cells
  • Tissue regeneration
  • Regenerative medicine
  • Immunomodulatory process

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Related Special Issues

Published Papers (6 papers)

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Research

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16 pages, 2848 KiB  
Article
Non-Cytokine Protein Profile of the Mesenchymal Stem Cell Secretome That Regulates the Androgen Production Pathway
by Hang-Soo Park, Rishi Man Chugh, Melissa R. Pergande, Esra Cetin, Hiba Siblini, Sahar Esfandyari, Stephanie M. Cologna and Ayman Al-Hendy
Int. J. Mol. Sci. 2022, 23(9), 4633; https://doi.org/10.3390/ijms23094633 - 22 Apr 2022
Cited by 7 | Viewed by 2421
Abstract
Polycystic ovary syndrome (PCOS) is the most common endocrine and metabolic disorder in reproductive-aged women, and it typically involves elevated androgen levels. Recently, it has been reported that human bone marrow mesenchymal stem cells (hBM-MSCs) can regulate androgen synthesis pathways. However, the details [...] Read more.
Polycystic ovary syndrome (PCOS) is the most common endocrine and metabolic disorder in reproductive-aged women, and it typically involves elevated androgen levels. Recently, it has been reported that human bone marrow mesenchymal stem cells (hBM-MSCs) can regulate androgen synthesis pathways. However, the details of the mechanism are still unclear. hBM-MSC-derived secreted factors (the secretome) are promising sources of cell-based therapy as they consist of various types of proteins. It is thus important to know which proteins interact with disease-implicated biomolecules. This work aimed to investigate which secretome components contain the key factor that inhibits testosterone synthesis. In this study, we fractionated hBM-MSC-conditioned media into three fractions based on their molecular weights and found that, of the three fractions, one had the ability to inhibit the androgen-producing genes efficiently. We also analyzed the components of this fraction and established a protein profile of the hBM-MSC secretome, which was shown to inhibit androgen synthesis. Our study describes a set of protein components present in the hBM-MSC secretome that can be used therapeutically to treat PCOS by regulating androgen production for the first time. Full article
(This article belongs to the Special Issue Role and Application of Stem Cells in Regenerative Medicine 3.0)
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19 pages, 6513 KiB  
Article
The Effect of Liposomal Curcumin as an Anti-Inflammatory Strategy on Lipopolysaccharide e from Porphyromonas gingivalis Treated Endothelial Committed Neural Crest Derived Stem Cells: Morphological and Molecular Mechanisms
by Francesca Diomede, Luigia Fonticoli, Simone Guarnieri, Ylenia Della Rocca, Thangavelu Soundara Rajan, Antonella Fontana, Oriana Trubiani, Guya Diletta Marconi and Jacopo Pizzicannella
Int. J. Mol. Sci. 2021, 22(14), 7534; https://doi.org/10.3390/ijms22147534 - 14 Jul 2021
Cited by 22 | Viewed by 3903
Abstract
Curcumin, a yellow polyphenol extracted from the turmeric root is used as a diet supplement. It exhibits anti-inflammatory, antioxidant, and antitumor properties by modulating different intracellular mechanisms. Due to their low solubility in water, the curcumin molecules must be encapsulated into liposomes to [...] Read more.
Curcumin, a yellow polyphenol extracted from the turmeric root is used as a diet supplement. It exhibits anti-inflammatory, antioxidant, and antitumor properties by modulating different intracellular mechanisms. Due to their low solubility in water, the curcumin molecules must be encapsulated into liposomes to improve the bioavailability and biomedical potential. For the periodontal tissue and systemic health, it is essential to regulate the local inflammatory response. In this study, the possible beneficial effect of liposomes loaded with curcumin (CurLIP) in neural crest-derived human periodontal ligament stem cells (hPDLSCs) and in endothelial-differentiated hPDLSCs (e-hPDLSCs) induced with an inflammatory stimulus (lipopolysaccharide obtained from Porphyromonas gingivalis, LPS-G) was evaluated. The CurLIP formulation exhibited a significant anti-inflammatory effect by the downregulation of Toll-like receptor-4 (TLR4)/Myeloid differentiation primary response 88 (MyD88)/nuclear factor kappa light chain enhancer of activated B cells (NFkB)/NLR Family Pyrin Domain Containing 3 (NLRP3)/Caspase-1/Interleukin (IL)-1β inflammation cascade and reactive oxygen species (ROS) formation. Moreover, the exposure to LPS-G caused significant alterations in the expression of epigenetic modifiers, such as DNA Methyltransferase 1 (DNMT1) and P300, while the CurLIP treatment showed physiological expression. Overall, our in vitro study provides novel mechanistic insights into the intracellular pathway exert by CurLIP in the regulation of inflammation and epigenetic modifications. Full article
(This article belongs to the Special Issue Role and Application of Stem Cells in Regenerative Medicine 3.0)
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17 pages, 2517 KiB  
Article
Injection of Porcine Adipose Tissue-Derived Stromal Cells by a Novel Waterjet Technology
by Marina Danalache, Jasmin Knoll, Walter Linzenbold, Markus Enderle, Tanja Abruzzese, Arnulf Stenzl and Wilhelm K. Aicher
Int. J. Mol. Sci. 2021, 22(8), 3958; https://doi.org/10.3390/ijms22083958 - 12 Apr 2021
Cited by 4 | Viewed by 2708
Abstract
Previously, we developed a novel, needle-free waterjet (WJ) technology capable of injecting viable cells by visual guided cystoscopy in the urethral sphincter. In the present study, we aimed to investigate the effect of WJ technology on cell viability, surface markers, differentiation and attachment [...] Read more.
Previously, we developed a novel, needle-free waterjet (WJ) technology capable of injecting viable cells by visual guided cystoscopy in the urethral sphincter. In the present study, we aimed to investigate the effect of WJ technology on cell viability, surface markers, differentiation and attachment capabilities, and biomechanical features. Porcine adipose tissue-derived stromal cells (pADSCs) were isolated, expanded, and injected by WJ technology. Cell attachment assays were employed to investigate cell–matrix interactions. Cell surface molecules were analyzed by flow cytometry. Cells injected by Williams Needle (WN), normal cannula, or not injected cells served as controls. Biomechanical properties were assessed by atomic force microscopy (AFM). pADSCs injected by the WJ were viable (85.9%), proliferated well, and maintained their in vitro adipogenic and osteogenic differentiation capacities. The attachment of pADSCs was not affected by WJ injection and no major changes were noted for cell surface markers. AFM measurements yielded a significant reduction of cellular stiffness after WJ injections (p < 0.001). WJ cell delivery satisfies several key considerations required in a clinical context, including the fast, simple, and reproducible delivery of viable cells. However, the optimization of the WJ device may be necessary to further reduce the effects on the biomechanical properties of cells. Full article
(This article belongs to the Special Issue Role and Application of Stem Cells in Regenerative Medicine 3.0)
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16 pages, 3133 KiB  
Article
Guide Cells Support Muscle Regeneration and Affect Neuro-Muscular Junction Organization
by Flavio L. Ronzoni, Nefele Giarratana, Stefania Crippa, Mattia Quattrocelli, Marco Cassano, Gabriele Ceccarelli, Laura Benedetti, Jens Van Herck, Maria G. Cusella De Angelis, Marco Vitale, Daniela Galli and Maurilio Sampaolesi
Int. J. Mol. Sci. 2021, 22(4), 1939; https://doi.org/10.3390/ijms22041939 - 16 Feb 2021
Cited by 12 | Viewed by 3140
Abstract
Muscular regeneration is a complex biological process that occurs during acute injury and chronic degeneration, implicating several cell types. One of the earliest events of muscle regeneration is the inflammatory response, followed by the activation and differentiation of muscle progenitor cells. However, the [...] Read more.
Muscular regeneration is a complex biological process that occurs during acute injury and chronic degeneration, implicating several cell types. One of the earliest events of muscle regeneration is the inflammatory response, followed by the activation and differentiation of muscle progenitor cells. However, the process of novel neuromuscular junction formation during muscle regeneration is still largely unexplored. Here, we identify by single-cell RNA sequencing and isolate a subset of vessel-associated cells able to improve myogenic differentiation. We termed them ‘guide’ cells because of their remarkable ability to improve myogenesis without fusing with the newly formed fibers. In vitro, these cells showed a marked mobility and ability to contact the forming myotubes. We found that these cells are characterized by CD44 and CD34 surface markers and the expression of Ng2 and Ncam2. In addition, in a murine model of acute muscle injury and regeneration, injection of guide cells correlated with increased numbers of newly formed neuromuscular junctions. Thus, we propose that guide cells modulate de novo generation of neuromuscular junctions in regenerating myofibers. Further studies are necessary to investigate the origin of those cells and the extent to which they are required for terminal specification of regenerating myofibers. Full article
(This article belongs to the Special Issue Role and Application of Stem Cells in Regenerative Medicine 3.0)
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Review

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16 pages, 291 KiB  
Review
A Narrative Review: Gingival Stem Cells as a Limitless Reservoir for Regenerative Medicine
by Luigia Fonticoli, Ylenia Della Rocca, Thangavelu Soundara Rajan, Giovanna Murmura, Oriana Trubiani, Stefano Oliva, Jacopo Pizzicannella, Guya Diletta Marconi and Francesca Diomede
Int. J. Mol. Sci. 2022, 23(8), 4135; https://doi.org/10.3390/ijms23084135 - 8 Apr 2022
Cited by 20 | Viewed by 2676
Abstract
The gingival tissue can be collected in an easy way and represent an accessible source to isolate gingival-derived mesenchymal stem cells (GMSCs). GMSCs are a subpopulation of dental-derived mesenchymal stem cells that show the mesenchymal stem cells (MSCs) features, such as differentiation abilities [...] Read more.
The gingival tissue can be collected in an easy way and represent an accessible source to isolate gingival-derived mesenchymal stem cells (GMSCs). GMSCs are a subpopulation of dental-derived mesenchymal stem cells that show the mesenchymal stem cells (MSCs) features, such as differentiation abilities and immunomodulatory properties. Dental-derived stem cells are also expandable in vitro with genomic stability and the possibility to maintain the stemness properties over a prolonged period of passages. Moreover, several preclinical studies have documented that the extracellular vesicles (EVs) released from GMSCs possess similar biological functions and therapeutic effects. The EVs may represent a promising tool in the cell-free regenerative therapy approach. The present review paper summarized the GMSCs, their multi-lineage differentiation capacities, immunomodulatory features, and the potential use in the treatment of several diseases in order to stimulate tissue regeneration. GMSCs should be considered a good stem cell source for potential applications in tissue engineering and regenerative dentistry. Full article
(This article belongs to the Special Issue Role and Application of Stem Cells in Regenerative Medicine 3.0)
27 pages, 294 KiB  
Review
Oral Bone Tissue Regeneration: Mesenchymal Stem Cells, Secretome, and Biomaterials
by Agnese Gugliandolo, Luigia Fonticoli, Oriana Trubiani, Thangavelu S. Rajan, Guya D. Marconi, Placido Bramanti, Emanuela Mazzon, Jacopo Pizzicannella and Francesca Diomede
Int. J. Mol. Sci. 2021, 22(10), 5236; https://doi.org/10.3390/ijms22105236 - 15 May 2021
Cited by 63 | Viewed by 5643
Abstract
In the last few decades, tissue engineering has become one of the most studied medical fields. Even if bone shows self-remodeling properties, in some cases, due to injuries or anomalies, bone regeneration can be required. In particular, oral bone regeneration is needed in [...] Read more.
In the last few decades, tissue engineering has become one of the most studied medical fields. Even if bone shows self-remodeling properties, in some cases, due to injuries or anomalies, bone regeneration can be required. In particular, oral bone regeneration is needed in the dentistry field, where the functional restoration of tissues near the tooth represents a limit for many dental implants. In this context, the application of biomaterials and mesenchymal stem cells (MSCs) appears promising for bone regeneration. This review focused on in vivo studies that evaluated bone regeneration using biomaterials with MSCs. Different biocompatible biomaterials were enriched with MSCs from different sources. These constructs showed an enhanced bone regenerative power in in vivo models. However, we discussed also a future perspective in tissue engineering using the MSC secretome, namely the conditioned medium and extracellular vesicles. This new approach has already shown promising results for bone tissue regeneration in experimental models. Full article
(This article belongs to the Special Issue Role and Application of Stem Cells in Regenerative Medicine 3.0)
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