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Biomedicines
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Mesenchymal Stem Cell Application in Regenerative Medicine: From Mechanisms to...
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Mesenchymal Stem Cell Application in Regenerative Medicine: From Mechanisms to Therapeutic Approaches

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Biomedical Engineering and Materials".

Deadline for manuscript submissions: closed (31 January 2024) | Viewed by 10300

Special Issue Editors

Dr. Giovanni Zito

E-Mail Website
Guest Editor
Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione, Palermo, Italy
Interests: MSC-pre conditioning for the treatment of acute liver injuries; iPSCs generation for the establishment of in vitro liver disease models; MSCs conditioned media molecular char-acterization (proteomic and transcriptomic approaches)
Dr. Vitale Miceli

E-Mail Website
Guest Editor
Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione, Palermo, Italy
Interests: MSC-pre conditioning for the treatment of lung diseases; MSCs conditioned media mo-lecular characterization (proteomic and transcriptomic approaches)

Special Issue Information

Dear Colleagues,

Mesenchymal stem cells (MSCs), first identified as non-hematopoietic multipotent stem cells with the ability to differentiate into cell types from the three embryonic sheets, are now very well established as source of cells with great therapeutic potential, specifically for tissue regeneration and repair-associated diseases. The therapeutic properties of MSCs have been examined in both preclinical and clinical settings for the treatment of various disorders, including cardiovascular, neurodegenerative, immune, lung, liver, kidney, and orthopedics diseases. MSCs are immunoprivileged, and this feature make these cells a useful tool to be applied in the field of cell therapy. In addition, MSCs possess immunomodulatory, trophic, angiogenic, and antioxidative properties, and all of these effects appear to be in part mediated by the production of a functional secretome. Indeed, in many in vitro and in vivo disease models, MSC-derived products have been identified as responsible for therapeutic effects. Therefore, it becomes crucial to further characterize and define the mechanisms by which MSCs exert their function. We hope that this special Issue will provide interesting insights that will expand our knowledge on how MSCs and derivatives can be used for different types of diseases in a selective manner.

Dr. Giovanni Zito
Dr. Vitale Miceli
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. Biomedicines is an international peer-reviewed open access monthly 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 2600 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

  • mesenchymal stromal/stem cells
  • cell therapy
  • cell free therapies
  • tissue regeneration
  • conditioned media
  • mechanisms of priming
  • immunomodulation
  • trophism
  • angiogenesis

Published Papers (6 papers)

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Research

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11 pages, 1318 KiB  
Article
Mesenchymal Stem Cells Reduce the Extracellular Mitochondrial DNA-Mediated TLR9 Activation in Neonatal Hyperoxia-Induced Lung Injury
by Young Eun Kim, So Yoon Ahn, Se In Sung, Misun Yang, Dong Kyung Sung, Won Soon Park and Yun Sil Chang
Biomedicines 2024, 12(3), 686; https://doi.org/10.3390/biomedicines12030686 - 19 Mar 2024
Viewed by 746
Abstract
Mitochondrial DNA (mtDNA) released from dead or injured cells can activate inflammation, and mesenchymal stem cell (MSC) transplantation can reduce inflammation and injury. However, it has not been tested whether the release of mtDNA can be reduced by MSC transplantation. We hypothesized that [...] Read more.
Mitochondrial DNA (mtDNA) released from dead or injured cells can activate inflammation, and mesenchymal stem cell (MSC) transplantation can reduce inflammation and injury. However, it has not been tested whether the release of mtDNA can be reduced by MSC transplantation. We hypothesized that the level of extracellular mtDNA would be increased after hyperoxia-induced lung injury but reduced after lung injury attenuation by MSC therapy in our newborn rat model. In an in vitro study using a rat lung epithelial L2 cell line, we found that the level of extracellular mtDNA was significantly increased with H2O2-induced cell death but reduced after MSC co-incubation. In an in vivo study, we confirmed that the levels of cell death, extracellular mtDNA, and inflammatory cytokines were significantly increased in hyperoxic newborn rat lungs but reduced after MSC transplantation. The levels of extracellular mtDNA were significantly and positively correlated with the levels of the inflammatory cytokines. The TLR9/MyD88/NF-κB pathway, which is activated by binding to mtDNA, was also significantly upregulated but downregulated after MSC transplantation. We found a significant positive correlation between inflammatory cytokines and extracellular mtDNA in intubated neonates. The levels of inflammatory cytokines and extracellular mtDNA changed over time in a similar pattern in transtracheal aspirate samples from intubated neonates. In conclusion, increased levels of extracellular mtDNA are associated with increased inflammation in hyperoxia-induced lung injury, and attenuation of lung inflammation by MSC therapy is associated with reduced levels of extracellular mtDNA. Full article
(This article belongs to the Special Issue Mesenchymal Stem Cell Application in Regenerative Medicine: From Mechanisms to Therapeutic Approaches)
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15 pages, 42205 KiB  
Article
Mesenchymal Stromal Cell on Liver Decellularised Extracellular Matrix for Tissue Engineering
by Stefania Croce, Lorenzo Cobianchi, Tamara Zoro, Francesca Dal Mas, Antonia Icaro Cornaglia, Elisa Lenta, Gloria Acquafredda, Annalisa De Silvestri, Maria Antonietta Avanzini, Livia Visai, Szandra Brambilla, Giovanna Bruni, Giulia Di Gravina, Andrea Pietrabissa, Luca Ansaloni and Andrea Peloso
Biomedicines 2022, 10(11), 2817; https://doi.org/10.3390/biomedicines10112817 - 4 Nov 2022
Cited by 2 | Viewed by 1753
Abstract
Background: In end-stage chronic liver disease, transplantation represents the only curative option. However, the shortage of donors results in the death of many patients. To overcome this gap, it is mandatory to develop new therapeutic options. In the present study, we decellularised pig [...] Read more.
Background: In end-stage chronic liver disease, transplantation represents the only curative option. However, the shortage of donors results in the death of many patients. To overcome this gap, it is mandatory to develop new therapeutic options. In the present study, we decellularised pig livers and reseeded them with allogeneic porcine mesenchymal stromal cells (pMSCs) to understand whether extracellular matrix (ECM) can influence and/or promote differentiation into hepatocyte-like cells (HLCs). Methods: After decellularisation with SDS, the integrity of ECM-scaffolds was examined by histological staining, immunofluorescence and scanning electron microscope. DNA quantification was used to assess decellularisation. pMSCs were plated on scaffolds by static seeding and maintained in in vitro culture for 21 days. At 3, 7, 14 and 21 days, seeded ECM scaffolds were evaluated for cellular adhesion and growth. Moreover, the expression of specific hepatic genes was performed by RT-PCR. Results: The applied decellularisation/recellularisation protocol was effective. The number of seeded pMSCs increased over the culture time points. Gene expression analysis of seeded pMSCs displayed a weak induction due to ECM towards HLCs. Conclusions: These results suggest that ECM may address pMSCs to differentiate in hepatocyte-like cells. However, only contact with liver-ECM is not enough to induce complete differentiation. Full article
(This article belongs to the Special Issue Mesenchymal Stem Cell Application in Regenerative Medicine: From Mechanisms to Therapeutic Approaches)
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12 pages, 2126 KiB  
Article
Amniotic Fluid-Derived Mesenchymal Stem/Stromal Cell-Derived Secretome and Exosomes Improve Inflammation in Human Intestinal Subepithelial Myofibroblasts
by Hector Katifelis, Eirini Filidou, Adriana Psaraki, Farinta Yakoub, Maria G. Roubelakis, Gesthimani Tarapatzi, Stergios Vradelis, Giorgos Bamias, George Kolios and Maria Gazouli
Biomedicines 2022, 10(10), 2357; https://doi.org/10.3390/biomedicines10102357 - 21 Sep 2022
Cited by 3 | Viewed by 1987
Abstract
Inflammatory Bowel Diseases (IBDs) are characterized by chronic relapsing inflammation of the gastrointestinal tract. The mesenchymal stem/stromal cell-derived secretome and secreted extracellular vesicles may offer novel therapeutic opportunities in patients with IBD. Thus, exosomes may be utilized as a novel cell-free approach for [...] Read more.
Inflammatory Bowel Diseases (IBDs) are characterized by chronic relapsing inflammation of the gastrointestinal tract. The mesenchymal stem/stromal cell-derived secretome and secreted extracellular vesicles may offer novel therapeutic opportunities in patients with IBD. Thus, exosomes may be utilized as a novel cell-free approach for IBD therapy. The aim of our study was to examine the possible anti-inflammatory effects of secretome/exosomes on an IBD-relevant, in vitro model of LPS-induced inflammation in human intestinal SubEpithelial MyoFibroblasts (SEMFs). The tested CM (Conditioned Media)/exosomes derived from a specific population of second-trimester amniotic fluid mesenchymal stem/stromal cells, the spindle-shaped amniotic fluid MSCs (SS-AF-MSCs), and specifically, their secreted exosomes could be utilized as a novel cell-free approach for IBD therapy. Therefore, we studied the effect of SS-AF-MSCs CM and exosomes on LPS-induced inflammation in SEMF cells. SS-AF-MSCs CM and exosomes were collected, concentrated, and then delivered into the cell cultures. Administration of both secretome and exosomes derived from SS-AF-MSCs reduced the severity of LPS-induced inflammation. Specifically, IL-1β, IL-6, TNF-α, and TLR-4 mRNA expression was decreased, while the anti-inflammatory IL-10 was elevated. Our results were also verified at the protein level, as secretion of IL-1β was significantly reduced. Overall, our results highlight a cell-free and anti-inflammatory therapeutic agent for potential use in IBD therapy. Full article
(This article belongs to the Special Issue Mesenchymal Stem Cell Application in Regenerative Medicine: From Mechanisms to Therapeutic Approaches)
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10 pages, 483 KiB  
Article
Therapeutic Efficacy and Mid-Term Durability of Urethral Sphincter Platelet-Rich Plasma Injections to Treat Postprostatectomy Stress Urinary Incontinence
by Ping-Jui Lee, Yuan-Hong Jiang and Hann-Chorng Kuo
Biomedicines 2022, 10(9), 2235; https://doi.org/10.3390/biomedicines10092235 - 8 Sep 2022
Cited by 2 | Viewed by 1281
Abstract
Platelet-rich plasma (PRP) is used for tissue repair and regeneration. Herein, we investigated the therapeutic efficacy and mid-term durability of injections of PRP into the urethral sphincter for the management of postprostatectomy incontinence (PPI). Thirty-nine patients with PPI that were refractory to conservative [...] Read more.
Platelet-rich plasma (PRP) is used for tissue repair and regeneration. Herein, we investigated the therapeutic efficacy and mid-term durability of injections of PRP into the urethral sphincter for the management of postprostatectomy incontinence (PPI). Thirty-nine patients with PPI that were refractory to conservative treatments were prospectively enrolled. They received repeated PRP urethral sphincter injections monthly for a total of four months. The primary endpoint was the Global Response Assessment (GRA) score after treatment. The secondary endpoints included changes in the stress urinary incontinence (SUI) visual analog scale (VAS) from baseline to the end of follow-up and urodynamic parameters from baseline to 3 months. The mean follow-up period after the entire treatment course was 21.0 ± 11.3 (range: 1.6–36.3) months. After PRP injections, the median GRA score with quartiles was 2.0 (1.0, 2.0). The SUI VAS and abdominal leak point pressure significantly improved from 6.9 ± 1.8 to 4.4 ± 2.3, p < 0.001, and from 74.8 ± 37.0 to 115.5 ± 57.9 cmH2O, p = 0.004, respectively, after the fourth PRP urethral sphincter injection. Following PRP urethral sphincter injections, the severity of SUI significantly reduced, indicating efficacy and mid-term durability as a novel treatment for PPI. Full article
(This article belongs to the Special Issue Mesenchymal Stem Cell Application in Regenerative Medicine: From Mechanisms to Therapeutic Approaches)
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Review

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25 pages, 1280 KiB  
Review
Role of Mesenchymal Stem/Stromal Cells in Modulating Ischemia/Reperfusion Injury: Current State of the Art and Future Perspectives
by Vitale Miceli, Matteo Bulati, Alessia Gallo, Gioacchin Iannolo, Rosalia Busà, Pier Giulio Conaldi and Giovanni Zito
Biomedicines 2023, 11(3), 689; https://doi.org/10.3390/biomedicines11030689 - 23 Feb 2023
Cited by 6 | Viewed by 1981
Abstract
Ischemia/reperfusion injury (IRI) is a multistep damage that occurs in several tissues when a blood flow interruption is inevitable, such as during organ surgery or transplantation. It is responsible for cell death and tissue dysfunction, thus leading, in the case of transplantation, to [...] Read more.
Ischemia/reperfusion injury (IRI) is a multistep damage that occurs in several tissues when a blood flow interruption is inevitable, such as during organ surgery or transplantation. It is responsible for cell death and tissue dysfunction, thus leading, in the case of transplantation, to organ rejection. IRI takes place during reperfusion, i.e., when blood flow is restored, by activating inflammation and reactive oxygen species (ROS) production, causing mitochondrial damage and apoptosis of parenchymal cells. Unfortunately, none of the therapies currently in use are definitive, prompting the need for new therapeutic approaches. Scientific evidence has proven that mesenchymal stem/stromal cells (MSCs) can reduce inflammation and ROS, prompting this cellular therapy to also be investigated for treatment of IRI. Moreover, it has been shown that MSC therapeutic effects were mediated in part by their secretome, which appears to be involved in immune regulation and tissue repair. For these reasons, mediated MSC paracrine function might be key for injury amelioration upon IRI damage. In this review, we highlight the scientific literature on the potential beneficial use of MSCs and their products for improving IRI outcomes in different tissues/organs, focusing in particular on the paracrine effects mediated by MSCs, and on the molecular mechanisms behind these effects. Full article
(This article belongs to the Special Issue Mesenchymal Stem Cell Application in Regenerative Medicine: From Mechanisms to Therapeutic Approaches)
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24 pages, 1006 KiB  
Review
Current Perspectives on Adult Mesenchymal Stromal Cell-Derived Extracellular Vesicles: Biological Features and Clinical Indications
by Giusi Alberti, Eleonora Russo, Simona Corrao, Rita Anzalone, Peter Kruzliak, Vitale Miceli, Pier Giulio Conaldi, Francesca Di Gaudio and Giampiero La Rocca
Biomedicines 2022, 10(11), 2822; https://doi.org/10.3390/biomedicines10112822 - 5 Nov 2022
Cited by 8 | Viewed by 1586
Abstract
Extracellular vesicles (EVs) constitute one of the main mechanisms by which cells communicate with the surrounding tissue or at distance. Vesicle secretion is featured by most cell types, and adult mesenchymal stromal cells (MSCs) of different tissue origins have shown the ability to [...] Read more.
Extracellular vesicles (EVs) constitute one of the main mechanisms by which cells communicate with the surrounding tissue or at distance. Vesicle secretion is featured by most cell types, and adult mesenchymal stromal cells (MSCs) of different tissue origins have shown the ability to produce them. In recent years, several reports disclosed the molecular composition and suggested clinical indications for EVs derived from adult MSCs. The parental cells were already known for their roles in different disease settings in regulating inflammation, immune modulation, or transdifferentiation to promote cell repopulation. Interestingly, most reports also suggested that part of the properties of parental cells were maintained by isolated EV populations. This review analyzes the recent development in the field of cell-free therapies, focusing on several adult tissues as a source of MSC-derived EVs and the available clinical data from in vivo models. Full article
(This article belongs to the Special Issue Mesenchymal Stem Cell Application in Regenerative Medicine: From Mechanisms to Therapeutic Approaches)
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