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Novel MSC Perspectives: From Cell Regulation to Tissue Regeneration 2.0
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Novel MSC Perspectives: From Cell Regulation to Tissue Regeneration 2.0

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 (10 June 2020) | Viewed by 28920

Special Issue Editors

Prof. Dr. Heba Abdelrazik

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Guest Editor
1. Department of Clinical Pathology, Immunology and Cell Therapy Unit, Cairo University, Cairo, Egypt
2. Department of Immunology and Translation Medicine, University of Genoa and San Martino Hospital, Genova, Italy
Interests: MSCs for immune-modulation and regenerative medicine; reprogramming, gene editing and target gene therapy; neural lineage differentiation; intercellular communication and drug interactions
Special Issues, Collections and Topics in MDPI journals
Dr. Giovanni Barbanti-Bròdano

E-Mail Website1 Website2
Guest Editor
Chirurgia Vertebrale Oncologica & Degenerativa (CVOD), Istituti Ortopedici Rizzoli, Via Pupilli 1, 40136 Bologna, Italy
Interests: MSCs interaction with biomaterials; MSCs for treatment of benign spine tumors; clinical use of MSCs from different sources
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Elena De Falco

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Guest Editor
Faculty of Pharmacy and Medicine, Department of Medico-Surgical Sciences and Biotechnologies, University of Rome Sapienza, C.so della Repubblica 79, 04100 Latina, Italy
Interests: cardiac-transdifferentiation of MSCs; MSC-based cell therapies in cardiovascular diseases and regenerative medicine; cell plasticity of MSCs; platelet lysate and MSCs
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Emanuele Giordano

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Guest Editor
Laboratory of Cellular and Molecular Engineering "Silvio Cavalcanti" - Department of Electrical, Electronic and Information Engineering "Guglielmo Marconi" (DEI), University of Bologna, Via Venezia 52, 47521 Cesena (FC), Italy; Health Sciences and Technologies - Interdepartmental Center for Industrial Research (HST-ICIR), University of Bologna, Via Tolara di Sopra 41/E, 40064 Ozzano dell’Emilia (BO), Italy; Advanced Research Center on Electronic Systems (ARCES), University of Bologna, Via Vincenzo Toffano 2/2, 40125 Bologna, Italy
Interests: tissue engineering for regenerative medicine; epigenetic regulation of gene expression; protocols in synthetic biology
Special Issues, Collections and Topics in MDPI journals
Dr. Alessandra Pelagalli

E-Mail Website
Guest Editor
Department of Veterinary Medicine and Animal Production, University of Naples Federico II, 80137 Naples, Italy
Interests: MSCs from domestic animal species; MSCs physiology and behavior for translational regenerative medicine; migration and proliferation of MSCs and role of Aquaporin (AQPs); MSCs, conditioned medium and microenvironment in physiological condition
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue is a continuation of our previous Special Issue "Novel MSC Perspectives: From Cell Regulation to Tissue Regeneration" (https://0-www-mdpi-com.brum.beds.ac.uk/journal/ijms/special_issues/novel_msc).

The development in understanding mesenchymal stem cell (MSC) biology, gene regulation, and intercellular interactions is promising for the evolution of therapeutic approaches in tissue regeneration, both in humans and in animals. Thanks to their exclusive capacity to self-renew and commitment towards defined cell lineages, MSCs offer novel perspectives and tools for clinical application in a safe and effective manner. Recent knowledge in the crosstalk between MSCs and the microenvironment has highlighted that key soluble modulators, specific signaling pathways, and/or the employment of biomaterials are able to foster a wide array of MSC properties, including migration, behavior, and also gene expression and cell fate. This provides new insights for the genetic manipulation, reprogramming, and/or gene editing of MSCs addressing also physical, biological, and biochemical properties of MSCs in order to boost their regenerative capabilities and tissue repair. Finally, studies concerning the use of MSCs from different sources for tissue regeneration in preclinical and clinical applications will allow translating the knowledge on MSC functions “from the bench to the bedside”. Accordingly, we invite investigators to contribute with novel findings in the field of MSCs and therefore help to bridge the gap between biology of regeneration and regenerative medicine and to encourage a novel progression towards MSC-based translational research.

Gruppo Italiano Staminali Mesenchimali (GISM)

Prof. Dr. Heba Abdelrazik
Dr. Giovanni Barbanti-Bròdano
Prof. Dr. Elena De Falco
Prof. Dr. Emanuele Giordano
Prof. Dr. Alessandra Pelagalli
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 (MSCs)
  • Regenerative medicine
  • Tissue engineering
  • Tissue repair
  • Bioactive materials
  • Cell differentiation
  • Cell behavior and cell fate
  • Translational medicine
  • Animal sources
  • Gene editing
  • Reprogramming

Related Special Issue

Published Papers (7 papers)

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Research

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23 pages, 4028 KiB  
Article
Differences in Mitochondrial Membrane Potential Identify Distinct Populations of Human Cardiac Mesenchymal Progenitor Cells
by Elisa Gambini, Ilenia Martinelli, Ilaria Stadiotti, Maria Cristina Vinci, Alessandro Scopece, Luana Eramo, Elena Sommariva, Jessica Resta, Sabrina Benaouadi, Elisa Cogliati, Adolfo Paolin, Angelo Parini, Giulio Pompilio and Frederique Savagner
Int. J. Mol. Sci. 2020, 21(20), 7467; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21207467 - 10 Oct 2020
Cited by 9 | Viewed by 3470
Abstract
Adult human cardiac mesenchymal progenitor cells (hCmPC) are multipotent resident populations involved in cardiac homeostasis and heart repair. Even if the mechanisms have not yet been fully elucidated, the stem cell differentiation is guided by the mitochondrial metabolism; however, mitochondrial approaches to identify [...] Read more.
Adult human cardiac mesenchymal progenitor cells (hCmPC) are multipotent resident populations involved in cardiac homeostasis and heart repair. Even if the mechanisms have not yet been fully elucidated, the stem cell differentiation is guided by the mitochondrial metabolism; however, mitochondrial approaches to identify hCmPC with enhanced stemness and/or differentiation capability for cellular therapy are not established. Here we demonstrated that hCmPCs sorted for low and high mitochondrial membrane potential (using a lipophilic cationic dye tetramethylrhodamine methyl ester, TMRM), presented differences in energy metabolism from preferential glycolysis to oxidative rates. TMRM-high cells are highly efficient in terms of oxygen consumption rate, basal and maximal respiration, and spare respiratory capacity compared to TMRM-low cells. TMRM-high cells showed characteristics of pre-committed cells and were associated with higher in vitro differentiation capacity through endothelial, cardiac-like, and, to a lesser extent, adipogenic and chondro/osteogenic cell lineage, when compared with TMRM-low cells. Conversely, TMRM-low showed higher self-renewal potential. To conclude, we identified two hCmPC populations with different metabolic profile, stemness maturity, and differentiation potential. Our findings suggest that metabolic sorting can isolate cells with higher regenerative capacity and/or long-term survival. This metabolism-based strategy to select cells may be broadly applicable to therapies. Full article
(This article belongs to the Special Issue Novel MSC Perspectives: From Cell Regulation to Tissue Regeneration 2.0)
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20 pages, 2261 KiB  
Article
An Injectable Hyaluronan–Methylcellulose (HAMC) Hydrogel Combined with Wharton’s Jelly-Derived Mesenchymal Stromal Cells (WJ-MSCs) Promotes Degenerative Disc Repair
by Un Yong Choi, Hari Prasad Joshi, Samantha Payne, Kyoung Tae Kim, Jae Won Kyung, Hyemin Choi, Michael J. Cooke, Su Yeon Kwon, Eun Ji Roh, Seil Sohn, Molly S. Shoichet and Inbo Han
Int. J. Mol. Sci. 2020, 21(19), 7391; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21197391 - 07 Oct 2020
Cited by 29 | Viewed by 5215
Abstract
Intervertebral disc (IVD) degeneration is one of the predominant causes of chronic low back pain (LBP), which is a leading cause of disability worldwide. Despite substantial progress in cell therapy for the treatment of IVD degeneration, significant challenges remain for clinical application. Here, [...] Read more.
Intervertebral disc (IVD) degeneration is one of the predominant causes of chronic low back pain (LBP), which is a leading cause of disability worldwide. Despite substantial progress in cell therapy for the treatment of IVD degeneration, significant challenges remain for clinical application. Here, we investigated the effectiveness of hyaluronan–methylcellulose (HAMC) hydrogels loaded with Wharton’s Jelly-derived mesenchymal stromal cell (WJ-MSCs) in vitro and in a rat coccygeal IVD degeneration model. Following induction of injury-induced IVD degeneration, female Sprague-Dawley rats were randomized into four groups to undergo a single intradiscal injection of the following: (1) phosphate buffered saline (PBS) vehicle, (2) HAMC, (3) WJ-MSCs (2 × 104 cells), and (4) WJ-MSCs-loaded HAMC (WJ-MSCs/HAMC) (n = 10/each group). Coccygeal discs were removed following sacrifice 6 weeks after implantation for radiologic and histologic analysis. We confirmed previous findings that encapsulation in HAMC increases the viability of WJ-MSCs for disc repair. The HAMC gel maintained significant cell viability in vitro. In addition, combined implantation of WJ-MSCs and HAMC significantly promoted degenerative disc repair compared to WJ-MSCs alone, presumably by improving nucleus pulposus cells viability and decreasing extracellular matrix degradation. Our results suggest that WJ-MSCs-loaded HAMC promotes IVD repair more effectively than cell injection alone and supports the potential clinical use of HAMC for cell delivery to arrest IVD degeneration or to promote IVD regeneration. Full article
(This article belongs to the Special Issue Novel MSC Perspectives: From Cell Regulation to Tissue Regeneration 2.0)
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13 pages, 1575 KiB  
Article
Secretome of Hypoxic Endothelial Cells Stimulates Bone Marrow-Derived Mesenchymal Stem Cells to Enhance Alternative Activation of Macrophages
by Kang-Ju Chou, Chih-Yang Hsu, Chien-Wei Huang, Hsin-Yu Chen, Shih-Hsiang Ou, Chien-Liang Chen, Po-Tsang Lee and Hua-Chang Fang
Int. J. Mol. Sci. 2020, 21(12), 4409; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21124409 - 21 Jun 2020
Cited by 7 | Viewed by 2402
Abstract
We intended to explore the cellular interaction between mesenchymal stem cells (MSCs) and injured endothelial cells leading to macrophage alternative polarization in healing kidney ischemic reperfusion injury. In vivo, the amounts of recruited macrophages were significantly mitigated by MSCs in the injured tissues, [...] Read more.
We intended to explore the cellular interaction between mesenchymal stem cells (MSCs) and injured endothelial cells leading to macrophage alternative polarization in healing kidney ischemic reperfusion injury. In vivo, the amounts of recruited macrophages were significantly mitigated by MSCs in the injured tissues, especially in the group using hematopoietic cell E- and L-selectin ligand (HCELL)-positive MSCs. Compared to controls, MSCs also enhanced expression of CD206 and CD163, which was further enhanced by HCELL expression. In vitro, analysis of cytokines involving macrophage polarization showed IL-13 rather than IL-4 from MSCs agreed with expression of macrophage CD206 in the presence of hypoxic endothelial cells. Among them, HCELL-positive MSCs in contact with hypoxic endothelial cells produced the greatest response, which were reduced without HCELL or using a transwell to prevent cell contact. With blockade of the respective cytokine, downregulated MSCs secretion of IL-13 and CD206 expression were observed using inhibitors of IFN-γ and TNF-α, but not using those of TGF-β and NO. With IFN-γ and TNF-α, MSCs IL-13 secretion and CD206 expression were upregulated. In conclusion, hypoxia induces endothelial cells producing multiple cytokines. Among them, IFN-γ and TNF-α that stimulate MSCs to secrete IL-13 but not IL-4, leading to alternative polarization. Full article
(This article belongs to the Special Issue Novel MSC Perspectives: From Cell Regulation to Tissue Regeneration 2.0)
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Review

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21 pages, 1125 KiB  
Review
Mesenchymal Stem Cell Treatment Perspectives in Peripheral Nerve Regeneration: Systematic Review
by Andrea Lavorato, Stefania Raimondo, Marina Boido, Luisa Muratori, Giorgia Durante, Fabio Cofano, Francesca Vincitorio, Salvatore Petrone, Paolo Titolo, Fulvio Tartara, Alessandro Vercelli and Diego Garbossa
Int. J. Mol. Sci. 2021, 22(2), 572; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22020572 - 08 Jan 2021
Cited by 50 | Viewed by 6399
Abstract
Traumatic peripheral nerve lesions affect hundreds of thousands of patients every year; their consequences are life-altering and often devastating and cause alterations in movement and sensitivity. Spontaneous peripheral nerve recovery is often inadequate. In this context, nowadays, cell therapy represents one of the [...] Read more.
Traumatic peripheral nerve lesions affect hundreds of thousands of patients every year; their consequences are life-altering and often devastating and cause alterations in movement and sensitivity. Spontaneous peripheral nerve recovery is often inadequate. In this context, nowadays, cell therapy represents one of the most innovative approaches in the field of nerve repair therapies. The purpose of this systematic review is to discuss the features of different types of mesenchymal stem cells (MSCs) relevant for peripheral nerve regeneration after nerve injury. The published literature was reviewed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A combination of the keywords “nerve regeneration”, “stem cells”, “peripheral nerve injury”, “rat”, and “human” were used. Additionally, a “MeSH” research was performed in PubMed using the terms “stem cells” and “nerve regeneration”. The characteristics of the most widely used MSCs, their paracrine potential, targeted stimulation, and differentiation potentials into Schwann-like and neuronal-like cells are described in this paper. Considering their ability to support and stimulate axonal growth, their remarkable paracrine activity, their presumed differentiation potential, their extremely low immunogenicity, and their high survival rate after transplantation, ADSCs appear to be the most suitable and promising MSCs for the recovery of peripheral nerve lesion. Clinical considerations are finally reported. Full article
(This article belongs to the Special Issue Novel MSC Perspectives: From Cell Regulation to Tissue Regeneration 2.0)
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21 pages, 1021 KiB  
Review
Potential of Extracellular Vesicle-Associated TSG-6 from Adipose Mesenchymal Stromal Cells in Traumatic Brain Injury
by Santiago Roura, Marta Monguió-Tortajada, Micaela Munizaga-Larroudé, Marta Clos-Sansalvador, Marcella Franquesa, Anna Rosell and Francesc E. Borràs
Int. J. Mol. Sci. 2020, 21(18), 6761; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21186761 - 15 Sep 2020
Cited by 13 | Viewed by 3066
Abstract
Multipotent mesenchymal stromal cells (MSC) represent a promising strategy for a variety of medical applications. Although only a limited number of MSC engraft and survive after in vivo cellular infusion, MSC have shown beneficial effects on immunomodulation and tissue repair. This indicates that [...] Read more.
Multipotent mesenchymal stromal cells (MSC) represent a promising strategy for a variety of medical applications. Although only a limited number of MSC engraft and survive after in vivo cellular infusion, MSC have shown beneficial effects on immunomodulation and tissue repair. This indicates that the contribution of MSC exists in paracrine signaling, rather than a cell-contact effect of MSC. In this review, we focus on current knowledge about tumor necrosis factor (TNF)-stimulated gene-6 (TSG-6) and mechanisms based on extracellular vesicles (EV) that govern long-lasting immunosuppressive and regenerative activity of MSC. In this context, in particular, we discuss the very robust set of findings by Jha and colleagues, and the opportunity to potentially extend their research focus on EV isolated in concentrated conditioned media (CCM) from adipose tissue derived MSC (ASC). Particularly, the authors showed that ASC-CCM mitigated visual deficits after mild traumatic brain injury in mice. TSG-6 knockdown ASC were, then, used to generate TSG-6-depleted CCM that were not able to replicate the alleviation of abnormalities in injured animals. In light of the presented results, we envision that the infusion of much distilled ASC-CCM could enhance the alleviation of visual abnormalities. In terms of EV research, the advantages of using size-exclusion chromatography are also highlighted because of the enrichment of purer and well-defined EV preparations. Taken together, this could further delineate and boost the benefit of using MSC-based regenerative therapies in the context of forthcoming clinical research testing in diseases that disrupt immune system homeostasis. Full article
(This article belongs to the Special Issue Novel MSC Perspectives: From Cell Regulation to Tissue Regeneration 2.0)
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17 pages, 2276 KiB  
Review
Effects of Lipids and Lipoproteins on Mesenchymal Stem Cells Used in Cardiac Tissue Regeneration
by Yi-Hsiung Lin, Lin Kang, Wen-Han Feng, Tsung-Lin Cheng, Wei-Chung Tsai, Hsuan-Ti Huang, Hsiang-Chun Lee and Chung-Hwan Chen
Int. J. Mol. Sci. 2020, 21(13), 4770; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21134770 - 05 Jul 2020
Cited by 11 | Viewed by 4020
Abstract
Mesenchymal stem cells (MSCs) have two characteristics of interest for this paper: the ability to self-renew, and the potential for multiple-lineage differentiation into various cells. MSCs have been used in cardiac tissue regeneration for over a decade. Adult cardiac tissue regeneration ability is [...] Read more.
Mesenchymal stem cells (MSCs) have two characteristics of interest for this paper: the ability to self-renew, and the potential for multiple-lineage differentiation into various cells. MSCs have been used in cardiac tissue regeneration for over a decade. Adult cardiac tissue regeneration ability is quite low; it cannot repair itself after injury, as the heart cells are replaced by fibroblasts and lose function. It is therefore important to search for a feasible way to repair and restore heart function through stem cell therapy. Stem cells can differentiate and provide a source of progenitor cells for cardiomyocytes, endothelial cells, and supporting cells. Studies have shown that the concentrations of blood lipids and lipoproteins affect cardiovascular diseases, such as atherosclerosis, hypertension, and obesity. Furthermore, the MSC lipid profiles, such as the triglyceride and cholesterol content, have been revealed by lipidomics, as well as their correlation with MSC differentiation. Abnormal blood lipids can cause serious damage to internal organs, especially heart tissue. In the past decade, the accumulated literature has indicated that lipids/lipoproteins affect stem cell behavior and biological functions, including their multiple lineage capability, and in turn affect the outcome of regenerative medicine. This review will focus on the effect of lipids/lipoproteins on MSC cardiac regenerative medicine, as well as the effect of lipid-lowering drugs in promoting cardiomyogenesis-associated MSC differentiation. Full article
(This article belongs to the Special Issue Novel MSC Perspectives: From Cell Regulation to Tissue Regeneration 2.0)
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24 pages, 405 KiB  
Review
Therapeutic Functions of Stem Cells from Oral Cavity: An Update
by Ji Won Yang, Ye Young Shin, Yoojin Seo and Hyung-Sik Kim
Int. J. Mol. Sci. 2020, 21(12), 4389; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21124389 - 19 Jun 2020
Cited by 22 | Viewed by 3781
Abstract
Adult stem cells have been developed as therapeutics for tissue regeneration and immune regulation due to their self-renewing, differentiating, and paracrine functions. Recently, a variety of adult stem cells from the oral cavity have been discovered, and these dental stem cells mostly exhibit [...] Read more.
Adult stem cells have been developed as therapeutics for tissue regeneration and immune regulation due to their self-renewing, differentiating, and paracrine functions. Recently, a variety of adult stem cells from the oral cavity have been discovered, and these dental stem cells mostly exhibit the characteristics of mesenchymal stem cells (MSCs). Dental MSCs can be applied for the replacement of dental and oral tissues against various tissue-damaging conditions including dental caries, periodontitis, and oral cancers, as well as for systemic regulation of excessive inflammation in immune disorders, such as autoimmune diseases and hypersensitivity. Therefore, in this review, we summarized and updated the types of dental stem cells and their functions to exert therapeutic efficacy against diseases. Full article
(This article belongs to the Special Issue Novel MSC Perspectives: From Cell Regulation to Tissue Regeneration 2.0)
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