Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

Journal Browser

Role and Application of Mesenchymal Stem Cells on Regenerative Medicine

Special Issue Editors
Special Issue Information
Keywords
Published Papers

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (31 August 2017) | Viewed by 115893

Share This Special Issue

Special Issue Editors

Prof. Dr. Adriano Piatelli

E-Mail Website
Advisory Board Member

School of Dentistry, Saint Camillus International University of Health and Medical Sciences, Via di Sant’Alessandro 8, 00131 Rome, Italy
Interests: bone regeneration; osseointegration; fracture implant; biomaterials; biocompatibility; bone resorption; bone biology
Special Issues, Collections and Topics in MDPI journals

Dr. Barbara Zavan

E-Mail Website
Guest Editor

Department of Biomedical Sciences, University of Padova, Viale Giuseppe Colombo, 3, 35131 Padova, Italy
Interests: stem cell; tissue regeneration; biomaterials; epigenetics; aging; extracellular matrix; inflammation; 3D printing
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,
The powerful decoy of regenerative medicine is based on the possibility to engineer cells and tissues of the human body to restore tissue, organs and parts lost to trauma or disease.

The development of novel biomaterials, able to drive the biological role of mesenchymal stem cells during regeneration process, is one of the most important biological fields developed in recent years.

Several works have led to important strides being made in the discovery of the rules of tissue formation, the interactions that occur between mesenchymal stem cells within an organ, the development of innovative biomaterials and the mechanisms underlying the regulation of tissue homeostasis.

Basic research on in vitro and in vivo models, related to tissue regeneration, will definitively contribute to the regenerative medicine field.

We invite you to contribute original articles that describe the regeneration and tissue repair process by means of the use of biomaterials, implant devices, stem cells, exosomes, and drugs in as many models and contexts as possible. Review articles describing our current knowledge on any aspect of regeneration and tissue repair are also welcome.

Prof. Barbara Zavan
Prof. Adriano Piattelli
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

Biomaterial
Tissue regeneration
Tissue engineering
Regenerative medicine
Implant surfaces
Bone regeneration
Osseointegration
Adult stem cells
Mesenchymal stem cell
Wound healing

Published Papers (14 papers)

Download All Papers

Research

Jump to: Review

3198 KiB

Open AccessArticle

Ascorbic Acid Attenuates Senescence of Human Osteoarthritic Osteoblasts

by Maximilian G. Burger, Amir Steinitz, Jeroen Geurts, Benjamin E. Pippenger, Dirk J. Schaefer, Ivan Martin, Andrea Barbero and Karoliina Pelttari

Int. J. Mol. Sci. 2017, 18(12), 2517; https://doi.org/10.3390/ijms18122517 - 24 Nov 2017

Cited by 18 | Viewed by 5147

Abstract

The accumulation of senescent cells is implicated in the pathology of several age-related diseases. While the clearance of senescent cells has been suggested as a therapeutic target for patients with osteoarthritis (OA), cellular senescence of bone-resident osteoblasts (OB) remains poorly explored. Since oxidative stress is a well-known inducer of cellular senescence, we here investigated the effect of antioxidant supplementation on the isolation efficiency, expansion, differentiation potential, and transcriptomic profile of OB from osteoarthritic subchondral bone. Bone chips were harvested from sclerotic and non-sclerotic regions of the subchondral bone of human OA joints. The application of 0.1 mM ascorbic acid-2-phosphate (AA) significantly increased the number of outgrowing cells and their proliferation capacity. This enhanced proliferative capacity showed a negative correlation with the amount of senescent cells and was accompanied by decreased expression of reactive oxygen species (ROS) in cultured OB. Expanded cells continued to express differentiated OB markers independently of AA supplementation and demonstrated no changes in their capacity to osteogenically differentiate. Transcriptomic analyses revealed that apoptotic, cell cycle–proliferation, and catabolic pathways were the main pathways affected in the presence of AA during OB expansion. Supplementation with AA can thus help to expand subchondral bone OB in vitro while maintaining their special cellular characteristics. The clearance of such senescent OB could be envisioned as a potential therapeutic target for the treatment of OA. Full article

(This article belongs to the Special Issue Role and Application of Mesenchymal Stem Cells on Regenerative Medicine)

► Show Figures

Figure 1

8213 KiB

Open AccessArticle

Vascular Endothelial Growth Factor Sequestration Enhances In Vivo Cartilage Formation

by Carolina M. Medeiros Da Cunha, Valeria Perugini, Petra Bernegger, Matteo Centola, Andrea Barbero, Anna L. Guildford, Matteo Santin, Andrea Banfi, Ivan Martin and Anna Marsano

Int. J. Mol. Sci. 2017, 18(11), 2478; https://doi.org/10.3390/ijms18112478 - 21 Nov 2017

Cited by 8 | Viewed by 4456

Abstract

Autologous chondrocyte transplantation for cartilage repair still has unsatisfactory clinical outcomes because of inter-donor variability and poor cartilage quality formation. Re-differentiation of monolayer-expanded human chondrocytes is not easy in the absence of potent morphogens. The Vascular Endothelial Growth Factor (VEGF) plays a master role in angiogenesis and in negatively regulating cartilage growth by stimulating vascular invasion and ossification. Therefore, we hypothesized that its sole microenvironmental blockade by either VEGF sequestration by soluble VEGF receptor-2 (Flk-1) or by antiangiogenic hyperbranched peptides could improve chondrogenesis of expanded human nasal chondrocytes (NC) freshly seeded on collagen scaffolds. Chondrogenesis of several NC donors was assessed either in vitro or ectopically in nude mice. VEGF blockade appeared not to affect NC in vitro differentiation, whereas it efficiently inhibited blood vessel ingrowth in vivo. After 8 weeks, in vivo glycosaminoglycan deposition was approximately two-fold higher when antiangiogenic approaches were used, as compared to the control group. Our data indicates that the inhibition of VEGF signaling, independently of the specific implementation mode, has profound effects on in vivo NC chondrogenesis, even in the absence of chondroinductive signals during prior culture or at the implantation site. Full article

(This article belongs to the Special Issue Role and Application of Mesenchymal Stem Cells on Regenerative Medicine)

► Show Figures

Graphical abstract

999 KiB

Open AccessArticle

The Contribution of Adipose Tissue-Derived Mesenchymal Stem Cells and Platelet-Rich Plasma to the Treatment of Chronic Equine Laminitis: A Proof of Concept

by Mario Angelone, Virna Conti, Cristiano Biacca, Beatrice Battaglia, Laura Pecorari, Francesco Piana, Giacomo Gnudi, Fabio Leonardi, Roberto Ramoni, Giuseppina Basini, Silvia Dotti, Sabrina Renzi, Maura Ferrari and Stefano Grolli

Int. J. Mol. Sci. 2017, 18(10), 2122; https://doi.org/10.3390/ijms18102122 - 11 Oct 2017

Cited by 31 | Viewed by 8838

Abstract

Laminitis, a highly debilitating disease of the foot in ungulates, is characterized by pathological changes of the complex lamellar structures that maintain the appendicular skeleton within the hoof. Laminitis is a multifactorial disease that involves perturbation of the vascular, hematological, and inflammatory homeostasis of the foot. Interestingly, the pathogenesis of the disease resembles what is observed in metabolic syndromes and sepsis-induced organ failure in humans and animals. We hypothesized that local administration of mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP) might contribute to establishing an anti-inflammatory and pro-angiogenic environment, and could stimulate the injured tissue in order to restore its functional integrity. According to this assumption, an experimental protocol based on the local intravenous administration of adipose tissue-derived MSCs (aMSCs) in combination with PRP was developed for the treatment of horses affected by chronic laminitis. Nine horses with severely compromised venograms (showing grade III and IV laminitis) that had been unsuccessfully treated with conventional therapies were enrolled. aMSCs and PRP (15 × 10⁶ cells resuspended in 15 mL of PRP) were injected into the lateral or medial digital vein three times, at one-month intervals. The first administration was performed with allogeneic aMSCs, while for the following administrations, autologous aMSCs were used. There was no adverse short-term reaction to the intravenous injection of aMSCs. In the long term, venograms outlined, in all subjects, a progressive amelioration of the vascularization of the foot. An improvement in the structure and function of the hoof was also observed. No adverse events were reported during the follow-up, and the horses returned to a comfortable quality of life. Although the number of animals enrolled in the study is limited, both clinical observations and venography demonstrated an enhancement in the condition of all horses, suggesting that the regenerative therapies in chronic laminitis could be useful, and are worthy of further investigation. Full article

(This article belongs to the Special Issue Role and Application of Mesenchymal Stem Cells on Regenerative Medicine)

► Show Figures

Graphical abstract

8480 KiB

Open AccessArticle

Fabrication of Innovative Silk/Alginate Microcarriers for Mesenchymal Stem Cell Delivery and Tissue Regeneration

by Sara Perteghella, Elisa Martella, Laura De Girolamo, Carlotta Perucca Orfei, Michela Pierini, Valentina Fumagalli, Domenica Valeria Pintacuda, Theodora Chlapanidas, Marco Viganò, Silvio Faragò, Maria Luisa Torre and Enrico Lucarelli

Int. J. Mol. Sci. 2017, 18(9), 1829; https://doi.org/10.3390/ijms18091829 - 23 Aug 2017

Cited by 35 | Viewed by 7710

Abstract

The aim of this study was to exploit silk fibroin’s properties to develop innovative composite microcarriers for mesenchymal stem cell (MSCs) adhesion and proliferation. Alginate microcarriers were prepared, added to silk fibroin solution, and then treated with ethanol to induce silk conformational transition. Microcarriers were characterized for size distribution, coating stability and homogeneity. Finally, in vitro cytocompatibility and suitability as delivery systems for MSCs were investigated. Results indicated that our manufacturing process is consistent and reproducible: silk/alginate microcarriers were stable, with spherical geometry, about 400 μm in average diameter, and fibroin homogeneously coated the surface. MSCs were able to adhere rapidly onto the microcarrier surface and to cover the surface of the microcarrier within three days of culture; moreover, on this innovative 3D culture system, stem cells preserved their metabolic activity and their multi-lineage differentiation potential. In conclusion, silk/alginate microcarriers represent a suitable support for MSCs culture and expansion. Since it is able to preserve MSCs multipotency, the developed 3D system can be intended for cell delivery, for advanced therapy and regenerative medicine applications. Full article

(This article belongs to the Special Issue Role and Application of Mesenchymal Stem Cells on Regenerative Medicine)

► Show Figures

Graphical abstract

8937 KiB

Open AccessArticle

Acceleration Mechanisms of Skin Wound Healing by Autologous Micrograft in Mice

by Shiro Jimi, Masahiko Kimura, Francesco De Francesco, Michele Riccio, Shuuji Hara and Hiroyuki Ohjimi

Int. J. Mol. Sci. 2017, 18(8), 1675; https://doi.org/10.3390/ijms18081675 - 02 Aug 2017

Cited by 36 | Viewed by 6667

Abstract

A micrograft technique, which minces tissue into micro-fragments >50 μm, has been recently developed. However, its pathophysiological mechanisms in wound healing are unclear yet. We thus performed a wound healing study using normal mice. A humanized mouse model of a skin wound with a splint was used. After total skin excision, tissue micro-fragments obtained by the Rigenera protocol were infused onto the wounds. In the cell tracing study, GFP-expressing green mice and SCID mice were used. Collagen stains including Picrosirius red (PSR) and immunohistological stains for α-smooth muscle actin (αSMA), CD31, transforming growth factor-β1 (TGF-β1) and neutrophils were evaluated for granulation tissue development. GFP-positive cells remained in granulation tissue seven days after infusion, but vanished after 13 days. Following the infusion of the tissue micrograft solution onto the wound, TGF-β1 expression was transiently upregulated in granulation tissue in the early phase. Subsequently, αSMA-expressing myofibroblasts increased in number in thickened granulation tissue with acceleration of neovascularization and collagen matrix maturation. On such granulation tissue, regenerative epithelial healing progressed, resulting in wound area reduction. Alternative alteration after the micrograft may have increased αSMA-expressing myofibroblasts in granulation tissue, which may act on collagen accumulation, neovascularization and wound contraction. All of these changes are favorable for epithelial regeneration on wound. Full article

(This article belongs to the Special Issue Role and Application of Mesenchymal Stem Cells on Regenerative Medicine)

► Show Figures

Graphical abstract

7023 KiB

Open AccessArticle

The Selective Centrifugation Ensures a Better In Vitro Isolation of ASCs and Restores a Soft Tissue Regeneration In Vivo

by Francesco De Francesco, Antonio Guastafierro, Gianfranco Nicoletti, Sergio Razzano, Michele Riccio and Giuseppe A. Ferraro

Int. J. Mol. Sci. 2017, 18(5), 1038; https://doi.org/10.3390/ijms18051038 - 12 May 2017

Cited by 17 | Viewed by 4683

Abstract

Autologous fat grafting procedures in plastic surgery have been extensively used to reinforce soft tissue in congenital or acquired tissue impairments. With this background, the aim of this study is firstly to examine the impact of a selective centrifugation on existing adipose stem cells (ASCs) in terms of stemness profile maintenance and, secondly, to investigate the effect of restoring volume in reconstruction on patients affected by soft tissue damage. After centrifugation, the fat graft products were separated into two layers and subsequently examined in vitro for the expression of CD34, CD90, CD117, CD105, CD29, CD31, CD44, CD73, CD133, CD14 and CD45 markers by flow cytometry and gene expression analyses were performed for Sox2, WNT3A, END, CD44, FUT4, COLL1, CTNNB1, hbEGF, KRTLG, MMP2 and VIM genes. The results showed that in the middle-high density (MHD) layer there was a peak concentration of ASCs, compared to another layer obtained after centrifugation. Research carried out on patients under treatment for soft tissue regeneration using cells obtained from MHD layer selection will be fundamental in comparative analysis. These studies will lead to an adequate standardization of outcomes, provided that treatment is performed through cell selection. Therefore, a unique procedure in tissue reconstruction and regeneration through fat grafting is presented here. Full article

(This article belongs to the Special Issue Role and Application of Mesenchymal Stem Cells on Regenerative Medicine)

► Show Figures

Figure 1

4111 KiB

Open AccessArticle

Minicircle Mediated Gene Delivery to Canine and Equine Mesenchymal Stem Cells

by Naomie Tidd, Jacob Michelsen, Bryan Hilbert and Jane C. Quinn

Int. J. Mol. Sci. 2017, 18(4), 819; https://doi.org/10.3390/ijms18040819 - 12 Apr 2017

Cited by 11 | Viewed by 4957

Abstract

Gene-directed tissue repair offers the clinician, human or veterinary, the chance to enhance cartilage regeneration and repair at a molecular level. Non-viral plasmid vectors have key biosafety advantages over viral vector systems for regenerative therapies due to their episomal integration however, conventional non-viral vectors can suffer from low transfection efficiency. Our objective was to identify and validate in vitro a novel non-viral gene expression vector that could be utilized for ex vivo and in vivo delivery to stromal-derived mesenchymal stem cells (MSCs). Minicircle plasmid DNA vector containing green fluorescent protein (GFP) was generated and transfected into adipose-derived MSCs from three species: canine, equine and rodent and transfection efficiency was determined. Both canine and rat cells showed transfection efficiencies of approximately 40% using minicircle vectors with equine cells exhibiting lower transfection efficiency. A Sox9-expressing minicircle vector was generated and transfected into canine MSCs. Successful transfection of the minicircle-Sox9 vector was confirmed in canine cells by Sox9 immunostaining. This study demonstrate the application and efficacy of a novel non-viral expression vector in canine and equine MSCs. Minicircle vectors have potential use in gene-directed regenerative therapies in non-rodent animal models for treatment of cartilage injury and repair. Full article

(This article belongs to the Special Issue Role and Application of Mesenchymal Stem Cells on Regenerative Medicine)

► Show Figures

Figure 1

2070 KiB

Open AccessArticle

Cellular Midpalatal Suture Changes after Rapid Maxillary Expansion in Growing Subjects: A Case Report

by Alberto Caprioglio, Rosamaria Fastuca, Piero Antonio Zecca, Matteo Beretta, Carlo Mangano, Adriano Piattelli, Aldo Macchi and Giovanna Iezzi

Int. J. Mol. Sci. 2017, 18(3), 615; https://doi.org/10.3390/ijms18030615 - 11 Mar 2017

Cited by 27 | Viewed by 5762

Abstract

The present case report aimed to investigate immediate histologic changes in midpalatal suture in humans following rapid maxillary expansion compared to control. Three patients (mean age 8.3 +/- 0.9 years) were enrolled in the case report and underwent midpalatal suture biopsy. Two patients underwent treatment before biopsy. The third patient did not show transversal maxillary deficiency and was enrolled as a control. Biopsy samples of midpalatal suture at 7 (subject 1) and 30 days (subject 2) after maxillary expansion as well as of one control (subject 3) were collected and processed for histology. In the control (subject 3) inter-digitations at the palatal suture gap were observed. At 7 days (subject 1) mature bone with small marrow spaces and trabecular bone with the peculiar storiform appearance inside the soft tissue and collagen fibers running parallel only in the central part were present. At 30 days (subject 2), a greater number of newly-formed bone trabeculae with a perpendicular orientation to the long axis of the suture could be seen. At 30 days the fibrous component of bone tissue was less represented compared to the sample at 7 days. Data from the preliminary histological results showed that bone formation was observed in the gap after rapid maxillary expansion, although the healing process was still ongoing. Full article

(This article belongs to the Special Issue Role and Application of Mesenchymal Stem Cells on Regenerative Medicine)

► Show Figures

Figure 1

1096 KiB

Open AccessArticle

Role of Cortico-Cancellous Heterologous Bone in Human Periodontal Ligament Stem Cell Xeno-Free Culture Studied by Synchrotron Radiation Phase-Contrast Microtomography

by Serena Mazzoni, Sara Mohammadi, Giuliana Tromba, Francesca Diomede, Adriano Piattelli, Oriana Trubiani and Alessandra Giuliani

Int. J. Mol. Sci. 2017, 18(2), 364; https://doi.org/10.3390/ijms18020364 - 10 Feb 2017

Cited by 19 | Viewed by 4349

Abstract

This study was designed to quantitatively demonstrate via three-dimensional (3D) images, through the Synchrotron Radiation Phase-Contrast Microtomography (SR-PhC-MicroCT), the osteoinductive properties of a cortico-cancellous scaffold (Osteobiol Dual Block—DB) cultured with human Periodontal Ligament Stem Cells (hPDLSCs) in xeno-free media. In vitro cultures of hPDLSCs, obtained from alveolar crest and horizontal fibers of the periodontal ligament, were seeded onto DB scaffolds and cultured in xeno-free media for three weeks. 3D images were obtained by SR-PhC-microCT after one and three weeks from culture beginning. MicroCT data were successively processed with a phase-retrieval algorithm based on the Transport of Intensity Equation (TIE). The chosen experimental method, previously demonstratively applied for the 3D characterization of the same constructs in not xeno-free media, quantitatively monitored also in this case the early stages of bone formation in basal and differentiating conditions. Interestingly, it quantitatively showed in the xeno-free environment a significant acceleration of the mineralization process, regardless of the culture (basal/differentiating) medium. This work showed in 3D that the DB guides the osteogenic differentiation of hPDLSCs in xeno-free cultures, in agreement with 2D observations and functional studies previously performed by some of the authors. Indeed, here we fully proved in 3D that expanded hPDLSCs, using xeno-free media formulation, not only provide the basis for Good Manufacturing Practice (preserving the stem cells’ morphological features and their ability to differentiate into mesenchymal lineage) but have to be considered, combined to DB scaffolds, as interesting candidates for potential clinical use in new custom made tissue-engineered constructs. Full article

(This article belongs to the Special Issue Role and Application of Mesenchymal Stem Cells on Regenerative Medicine)

► Show Figures

Figure 1

19830 KiB

Open AccessArticle

Micro-Computed Tomography Detection of Gold Nanoparticle-Labelled Mesenchymal Stem Cells in the Rat Subretinal Layer

by Pooi Ling Mok, Sue Ngein Leow, Avin Ee-Hwan Koh, Hairul Harun Mohd Nizam, Suet Lee Shirley Ding, Chi Luu, Raduan Ruhaslizan, Hon Seng Wong, Wan Haslina Wan Abdul Halim, Min Hwei Ng, Ruszymah Binti Hj. Idrus, Shiplu Roy Chowdhury, Catherine Mae-Lynn Bastion, Suresh Kumar Subbiah, Akon Higuchi, Abdullah A. Alarfaj and Kong Yong Then

Int. J. Mol. Sci. 2017, 18(2), 345; https://doi.org/10.3390/ijms18020345 - 08 Feb 2017

Cited by 22 | Viewed by 8519

Abstract

Mesenchymal stem cells are widely used in many pre-clinical and clinical settings. Despite advances in molecular technology; the migration and homing activities of these cells in in vivo systems are not well understood. Labelling mesenchymal stem cells with gold nanoparticles has no cytotoxic effect and may offer suitable indications for stem cell tracking. Here, we report a simple protocol to label mesenchymal stem cells using 80 nm gold nanoparticles. Once the cells and particles were incubated together for 24 h, the labelled products were injected into the rat subretinal layer. Micro-computed tomography was then conducted on the 15th and 30th day post-injection to track the movement of these cells, as visualized by an area of hyperdensity from the coronal section images of the rat head. In addition, we confirmed the cellular uptake of the gold nanoparticles by the mesenchymal stem cells using transmission electron microscopy. As opposed to other methods, the current protocol provides a simple, less labour-intensive and more efficient labelling mechanism for real-time cell tracking. Finally, we discuss the potential manipulations of gold nanoparticles in stem cells for cell replacement and cancer therapy in ocular disorders or diseases. Full article

(This article belongs to the Special Issue Role and Application of Mesenchymal Stem Cells on Regenerative Medicine)

► Show Figures

Figure 1

4167 KiB

Open AccessArticle

Cannabidiol Modulates the Expression of Alzheimer’s Disease-Related Genes in Mesenchymal Stem Cells

by Rosaliana Libro, Francesca Diomede, Domenico Scionti, Adriano Piattelli, Gianpaolo Grassi, Federica Pollastro, Placido Bramanti, Emanuela Mazzon and Oriana Trubiani

Int. J. Mol. Sci. 2017, 18(1), 26; https://doi.org/10.3390/ijms18010026 - 23 Dec 2016

Cited by 74 | Viewed by 20211

Abstract

Mesenchymal stem cells (MSCs) have emerged as a promising tool for the treatment of several neurodegenerative disorders, including Alzheimer’s disease (AD). The main neuropathological hallmarks of AD are senile plaques, composed of amyloid beta (Aβ), and neurofibrillary tangles, formed by hyperphosphorylated tau. However, current therapies for AD have shown limited efficacy. In this study, we evaluated whether pre-treatment with cannabidiol (CBD), at 5 μM concentration, modulated the transcriptional profile of MSCs derived from gingiva (GMSCs) in order to improve their therapeutic potential, by performing a transcriptomic analysis by the next-generation sequencing (NGS) platform. By comparing the expression profiles between GMSCs treated with CBD (CBD-GMSCs) and control GMSCs (CTR-GMSCs), we found that CBD led to the downregulation of genes linked to AD, including genes coding for the kinases responsible of tau phosphorylation and for the secretases involved in Aβ generation. In parallel, immunocytochemistry analysis has shown that CBD inhibited the expression of GSK3β, a central player in AD pathogenesis, by promoting PI3K/Akt signalling. In order to understand through which receptor CBD exerted these effects, we have performed pre-treatments with receptor antagonists for the cannabinoid receptors (SR141716A and AM630) or for the vanilloid receptor 1 (TRPVI). Here, we have proved that TRPV1 was able to mediate the modulatory effect of CBD on the PI3K/Akt/GSK3β axis. In conclusion, we have found that pre-treatment with CBD prevented the expression of proteins potentially involved in tau phosphorylation and Aβ production in GMSCs. Therefore, we suggested that GMSCs preconditioned with CBD possess a molecular profile that might be more beneficial for the treatment of AD. Full article

(This article belongs to the Special Issue Role and Application of Mesenchymal Stem Cells on Regenerative Medicine)

► Show Figures

Figure 1

Review

Jump to: Research

537 KiB

Open AccessReview

Can Youthful Mesenchymal Stem Cells from Wharton’s Jelly Bring a Breath of Fresh Air for COPD?

by Andrzej M. Janczewski, Joanna Wojtkiewicz, Ewa Malinowska and Anna Doboszyńska

Int. J. Mol. Sci. 2017, 18(11), 2449; https://doi.org/10.3390/ijms18112449 - 18 Nov 2017

Cited by 10 | Viewed by 6859

Abstract

Chronic obstructive pulmonary disease (COPD) is a major global cause of morbidity and mortality, projected to become the 3rd cause of disease mortality worldwide by 2020. COPD is characterized by persistent and not fully reversible airflow limitation that is usually progressive and is associated with an abnormal chronic inflammatory response of the lung to noxious agents including cigarette smoke. Currently available therapeutic strategies aim to ease COPD symptoms but cannot prevent its progress or regenerate physiological lung structure or function. The urgently needed new approaches for the treatment of COPD include stem cell therapies among which transplantation of mesenchymal stem cells derived from Wharton’s jelly (WJ-MSCs) emerges as a promising therapeutic strategy because of the unique properties of these cells. The present review discusses the main biological properties of WJ-MSCs pertinent to their potential application for the treatment of COPD in the context of COPD pathomechanisms with emphasis on chronic immune inflammatory processes that play key roles in the development and progression of COPD. Full article

(This article belongs to the Special Issue Role and Application of Mesenchymal Stem Cells on Regenerative Medicine)

► Show Figures

Figure 1

231 KiB

Open AccessReview

Adipose Tissue as a Strategic Source of Mesenchymal Stem Cells in Bone Regeneration: A Topical Review on the Most Promising Craniomaxillofacial Applications

by Francesco Paduano, Massimo Marrelli, Massimiliano Amantea, Carlo Rengo, Sandro Rengo, Michel Goldberg, Gianrico Spagnuolo and Marco Tatullo

Int. J. Mol. Sci. 2017, 18(10), 2140; https://doi.org/10.3390/ijms18102140 - 13 Oct 2017

Cited by 87 | Viewed by 5704

Abstract

Bone regeneration in craniomaxillofacial surgery represents an issue that involves both surgical and aesthetic aspects. The most recent studies on bone tissue engineering involving adipose-derived stromal/stem cells (ASCs) have clearly demonstrated that such cells can play a crucial role in the treatment of craniomaxillofacial defects, given their strong commitment towards the osteogenic phenotype. A deeper knowledge of the molecular mechanisms underlying ASCs is crucial for a correct understanding of the potentialities of ASCs-based therapies in the most complex maxillofacial applications. In this topical review, we analyzed the molecular mechanisms of ASCs related to their support toward angiogenesis and osteogenesis, during bone regeneration. Moreover, we analyzed both case reports and clinical trials reporting the most promising clinical applications of ASCs in the treatment of craniomaxillofacial defects. Our study aimed to report the main molecular and clinical features shown by ASCs, used as a therapeutic support in bone engineering, as compared to the use of conventional autologous and allogeneic bone grafts. Full article

(This article belongs to the Special Issue Role and Application of Mesenchymal Stem Cells on Regenerative Medicine)

► Show Figures

Graphical abstract

2943 KiB

Open AccessReview

Mesenchymal Stem Cells from Adipose Tissue in Clinical Applications for Dermatological Indications and Skin Aging

by Meenakshi Gaur, Marek Dobke and Victoria V. Lunyak

Int. J. Mol. Sci. 2017, 18(1), 208; https://doi.org/10.3390/ijms18010208 - 20 Jan 2017

Cited by 125 | Viewed by 20575

Abstract

Operating at multiple levels of control, mesenchymal stem cells from adipose tissue (ADSCs) communicate with organ systems to adjust immune response, provide signals for differentiation, migration, enzymatic reactions, and to equilibrate the regenerative demands of balanced tissue homeostasis. The identification of the mechanisms by which ADSCs accomplish these functions for dermatological rejuvenation and wound healing has great potential to identify novel targets for the treatment of disorders and combat aging. Herein, we review new insights into the role of adipose-derived stem cells in the maintenance of dermal and epidermal homeostasis, and recent advances in clinical applications of ADSCs related to dermatology. Full article

(This article belongs to the Special Issue Role and Application of Mesenchymal Stem Cells on Regenerative Medicine)

► Show Figures