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Stem Cells Application in Clinical Practice: Advances and Challenges
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Stem Cells Application in Clinical Practice: Advances and Challenges

A special issue of Genes (ISSN 2073-4425). This special issue belongs to the section "Human Genomics and Genetic Diseases".

Deadline for manuscript submissions: closed (25 October 2019) | Viewed by 23409

Special Issue Editors

Dr. Anthony Atala

grade E-Mail Website
Guest Editor
Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27101, USA
Interests: regenerative medicine; stem cells; tissue engineering
Prof. Dr. Dragan Primorac

E-Mail Website
Guest Editor
1. Eberly College of Science, Penn State University, 517 Thomas St, State Coll, PA 16803, USA
2. St. Catherine Hospital and Universities of Split, Osijek and Rijeka, 49210 Zabok, Croatia
Interests: personalised medicine; stem cells; pharmacogenetics; paediatrics; DNA analysis; human diseases; bone diseases; forensic genetics; population genetics

Special Issue Information

Dear Colleagues,

The use of stem cells (SCs) and, in general, of synthetic biology approaches to treat disease has significant promise. Likewise, enthusiasm for SC therapy is running high within the medical community of researchers and patients. Among the most promising SCs are mesenchymal fetal and adult stem cells, such as those derived from cord blood, bone marrow, and fat, which may possess anti-inflammatory, immunomodulatory, antiapoptotic, or angiogenic properties. Amnion-derived stem cells (ADSCs) have more recently been isolated. ADSCs are multipotent stem cells with intermediate characteristics between embryonic and adult stem cells, showing the ability to differentiate into cell types from all three germ layers.

Many aspects concerning the biology of stem cells, their differential potential in vitro and in vivo, as well as their mechanisms of action remain unsolved. However, the use of SCs requires a high level of competence during all phases of the procedure, from cell isolation to clinical trial evaluation.  Finally, the clinical application of SCs fosters numerous ethical and safety discussions.

Therefore, this Special Issue of Genes will place a special emphasis on basic, translational, and clinical research in stem cell therapeutics and regenerative medicine. We welcome research articles as well as reviews addressing different issues related to stem cells.

Topics of interest include but are not limited to the following:

  • Sources, isolation, nature, and molecular characterization of SCs
  • Phenotyping of SCs
  • Developmental potential, biological functions, and therapeutic uses of SCs
  • Clinical studies using stem cells
  • Adult and fetal stem cells

Prof. Anthony Atala
Prof. Dragan Primorac
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. Genes 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

  • stem cells
  • human disease
  • mesenchymal stem/stromal cells
  • adult stem cells
  • fetal stem cells
  • stromal vascular fraction (SVF)
  • stem cell therapy
  • regenerative medicine

Published Papers (5 papers)

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Research

26 pages, 817 KiB  
Article
Sex-Specific Transcriptome Differences in Human Adipose Mesenchymal Stem Cells
by Eva Bianconi, Raffaella Casadei, Flavia Frabetti, Carlo Ventura, Federica Facchin and Silvia Canaider
Genes 2020, 11(8), 909; https://0-doi-org.brum.beds.ac.uk/10.3390/genes11080909 - 08 Aug 2020
Cited by 23 | Viewed by 5463
Abstract
In humans, sexual dimorphism can manifest in many ways and it is widely studied in several knowledge fields. It is increasing the evidence that also cells differ according to sex, a correlation still little studied and poorly considered when cells are used in [...] Read more.
In humans, sexual dimorphism can manifest in many ways and it is widely studied in several knowledge fields. It is increasing the evidence that also cells differ according to sex, a correlation still little studied and poorly considered when cells are used in scientific research. Specifically, our interest is on the sex-related dimorphism on the human mesenchymal stem cells (hMSCs) transcriptome. A systematic meta-analysis of hMSC microarrays was performed by using the Transcriptome Mapper (TRAM) software. This bioinformatic tool was used to integrate and normalize datasets from multiple sources and allowed us to highlight chromosomal segments and genes differently expressed in hMSCs derived from adipose tissue (hADSCs) of male and female donors. Chromosomal segments and differentially expressed genes in male and female hADSCs resulted to be related to several processes as inflammation, adipogenic and neurogenic differentiation and cell communication. Obtained results lead us to hypothesize that the donor sex of hADSCs is a variable influencing a wide range of stem cell biologic processes. We believe that it should be considered in biologic research and stem cell therapy. Full article
(This article belongs to the Special Issue Stem Cells Application in Clinical Practice: Advances and Challenges)
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20 pages, 1552 KiB  
Article
Extracellular Vesicles Derived from Human Gingival Mesenchymal Stem Cells: A Transcriptomic Analysis
by Serena Silvestro, Luigi Chiricosta, Agnese Gugliandolo, Jacopo Pizzicannella, Francesca Diomede, Placido Bramanti, Oriana Trubiani and Emanuela Mazzon
Genes 2020, 11(2), 118; https://0-doi-org.brum.beds.ac.uk/10.3390/genes11020118 - 21 Jan 2020
Cited by 51 | Viewed by 3450
Abstract
Human gingival mesenchymal stem cells (hGMSCs) have outstanding characteristics of proliferation and are able to differentiate into osteogenic, chondrogenic, adipogenic, and neurogenic cell lineages. The extracellular vesicles (EVs) secreted by hGMSCs contain proteins, lipids, mRNA and microRNA have emerged as important mediators of [...] Read more.
Human gingival mesenchymal stem cells (hGMSCs) have outstanding characteristics of proliferation and are able to differentiate into osteogenic, chondrogenic, adipogenic, and neurogenic cell lineages. The extracellular vesicles (EVs) secreted by hGMSCs contain proteins, lipids, mRNA and microRNA have emerged as important mediators of cell-to-cell communication. In this study, we analyzed the transcriptome of hGMSCs-derived EVs using Next Generation Sequencing (NGS). The functional evaluation of the transcriptome highlighted 26 structural protein classes and the presence of “non-coding RNAs”. Our results showed that EVs contain several growth factors such as Transforming Growth Factor-β (TGF-β), Fibroblast Growth Factor (FGF), and Vascular Endothelial Growth Factors (VEGF) implicated in osteoblast differentiation and in angiogenetic process. Furthermore, the transcriptomic analysis showed the presence of glial cell-derived neurotrophic factor (GDNF) family ligands and neurotrophins involved in neuronal development. The NGS analysis also identified the presence of several interleukins among which some with anti-inflammatory action. Moreover, the transcriptome profile of EVs contained members of the Wnt family, involved in several biological processes, such as cellular proliferation and tissue regeneration. In conclusion, the huge amount of growth factors included in the hGMSCs-derived EVs could make them a big resource in regenerative medicine. Full article
(This article belongs to the Special Issue Stem Cells Application in Clinical Practice: Advances and Challenges)
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9 pages, 214 KiB  
Article
A 24-Month Follow-Up Study of the Effect of Intra-Articular Injection of Autologous Microfragmented Fat Tissue on Proteoglycan Synthesis in Patients with Knee Osteoarthritis
by Igor Borić, Damir Hudetz, Eduard Rod, Željko Jeleč, Trpimir Vrdoljak, Andrea Skelin, Ozren Polašek, Mihovil Plečko, Irena Trbojević-Akmačić, Gordan Lauc and Dragan Primorac
Genes 2019, 10(12), 1051; https://0-doi-org.brum.beds.ac.uk/10.3390/genes10121051 - 17 Dec 2019
Cited by 43 | Viewed by 4434
Abstract
Osteoarthritis (OA) is a widely prevalent disease worldwide, and with an increasingly ageing society, it has become a challenge for the field of regenerative medicine. OA is a disease process involving multiple joint tissues, including those not visible on radiography, and is a [...] Read more.
Osteoarthritis (OA) is a widely prevalent disease worldwide, and with an increasingly ageing society, it has become a challenge for the field of regenerative medicine. OA is a disease process involving multiple joint tissues, including those not visible on radiography, and is a complex disease process with multiple phenotypes that require evaluation by a multimodality imaging assessment. The purpose of this study was to evaluate the effect of micro-fragmented fat tissue intra-articular injection 24 months after application in two ways: Indirectly using functional magnetic resonance imaging (MRI) assessment analyzing the glycosaminoglycans (GAG) content in cartilage by means of delayed gadolinium (Gd)-enhanced magnetic resonance imaging of cartilage (dGEMRIC), as well as clinical outcome on observed level of GAG using standard orthopedic physical examination including VAS assessment. In our previous study assessing comprehensive results after 12 months, the dGEMRIC results have drawn attention. The present study explores the long-term effect of intra-articular injection of autologous microfragmented adipose tissue to host chondrocytes and cartilage proteoglycans in patients with knee OA. A prospective, non-randomized, interventional, single-center, open-label clinical trial was conducted from January 2016 to April 2018. A total of 17 patients were enrolled in the study, and 32 knees were assessed in a 12-month follow-up, but only 10 patients of them with 18 knees are included in a 24-month follow-up. The rest of the seven patients dropped out of the study 12 months after follow-up: three patients underwent knee arthroplasty, and the remaining four did not fulfil the basic criteria of 24 months involvement in the study. Surgical intervention (lipoaspiration), followed by tissue processing and intra-articular injection of the final microfragmented adipose tissue product into the affected knee(s), was performed in all patients. Patients were assessed for a visual analog scale (VAS), dGEMRIC at the baseline, three, six, 12 and 24 months after the treatment. A magnetic resonance sequence in dGEMRIC due to infiltration of the anionic, negatively-charged contrast gadopentetate dimeglumine (Gd-DTPA2) into the cartilage indicated that the contents of cartilage glycosaminoglycans significantly increased in specific areas of the treated knee joint. Our results suggest that this method of single intra-articular injection of autologous microfragmented adipose tissue improves GAG content on a significant scale, with over half of the measurements suggesting relevant improvement 24 months after intra-articular injection opposed to the expected GAG decrease over the natural course of the disease. Full article
(This article belongs to the Special Issue Stem Cells Application in Clinical Practice: Advances and Challenges)
12 pages, 892 KiB  
Article
Periodontitis and Tooth Loss Have Negative Systemic Impact on Circulating Progenitor Cell Levels: A Clinical Study
by Gaetano Isola, Antonino Lo Giudice, Alessandro Polizzi, Angela Alibrandi, Romeo Patini and Sebastiano Ferlito
Genes 2019, 10(12), 1022; https://0-doi-org.brum.beds.ac.uk/10.3390/genes10121022 - 07 Dec 2019
Cited by 68 | Viewed by 4707
Abstract
The aim of the present study was to investigate the association and impact of periodontitis and tooth loss on a subtype of endothelial progenitor cell (EPC) levels (CD133+/KDR+). Furthermore, the objective was to determine if the periodontal status influenced [...] Read more.
The aim of the present study was to investigate the association and impact of periodontitis and tooth loss on a subtype of endothelial progenitor cell (EPC) levels (CD133+/KDR+). Furthermore, the objective was to determine if the periodontal status influenced CD133+/KDR+ levels. In all, 88 patients with periodontitis and 79 healthy controls (HCs) were enrolled in the study. Enrolled patients were examined and characterized by clinical and blood sample analysis. Spearman’s correlation test was applied in order to assess the interdependence between CD133+/KDR+ levels and all periodontal parameters. In order to estimate a statistically significant trend (p-trend) for ordered CD133++/KDR+ quartiles, the Jonckheere–Terpstra test was applied for all variables. Patients in the periodontitis group presented significantly lower CD133+/KDR+ levels (66.4 (45.5–269.6 cells/µL)) compared to the HC group (76.7 (24.3–313.2 cells/µL), p < 0.001). Lower CD133+/KDR+ levels negatively correlated with C-reactive protein (CRP), with the number of teeth, and with all periodontal parameters (p < 0.001). Moreover, there was a proportional increase in CD133+/KDR+ levels with a progressive increase in number of teeth (p-trend < 0.001), while there was a proportional decrease in CD133+/KDR+ levels with a proportional increase in clinical attachment level (CAL, p-trend = 0.003), probing depth (PD, p-trend = 0.007), and bleeding sites (bleeding on probing (BOP), p-trend < 0.001) as an extent measure of periodontitis. This study demonstrated that patients with periodontitis presented significantly lower CD133+/KDR+ levels compared to HCs. Moreover, all patients presented an increase in the CD133+/KDR+ EPC levels with an extended level of periodontitis and tooth loss. Full article
(This article belongs to the Special Issue Stem Cells Application in Clinical Practice: Advances and Challenges)
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11 pages, 4024 KiB  
Communication
Immunophenotyping of a Stromal Vascular Fraction from Microfragmented Lipoaspirate Used in Osteoarthritis Cartilage Treatment and Its Lipoaspirate Counterpart
by Denis Polancec, Lucija Zenic, Damir Hudetz, Igor Boric, Zeljko Jelec, Eduard Rod, Trpimir Vrdoljak, Andrea Skelin, Mihovil Plecko, Mirjana Turkalj, Boro Nogalo and Dragan Primorac
Genes 2019, 10(6), 474; https://0-doi-org.brum.beds.ac.uk/10.3390/genes10060474 - 21 Jun 2019
Cited by 23 | Viewed by 4486
Abstract
Osteoarthritis (OA) is a degenerative joint disease accompanied by pain and loss of function. Adipose tissue harbors mesenchymal stem/stromal cells (MSC), or medicinal signaling cells as suggested by Caplan (Caplan, 2017), used in autologous transplantation in many clinical settings. The aim of the [...] Read more.
Osteoarthritis (OA) is a degenerative joint disease accompanied by pain and loss of function. Adipose tissue harbors mesenchymal stem/stromal cells (MSC), or medicinal signaling cells as suggested by Caplan (Caplan, 2017), used in autologous transplantation in many clinical settings. The aim of the study was to characterize a stromal vascular fraction from microfragmented lipoaspirate (SVF-MLA) applied for cartilage treatment in OA and compare it to that of autologous lipoaspirate (SVF-LA). Samples were first stained using a DuraClone SC prototype tube for the surface detection of CD31, CD34, CD45, CD73, CD90, CD105, CD146 and LIVE/DEAD Yellow Fixable Stain for dead cell detection, followed by DRAQ7 cell nuclear dye staining, and analyzed by flow cytometry. In SVF-LA and SVF-MLA samples, the following population phenotypes were identified within the CD45− fraction: CD31+CD34+CD73±CD90±CD105±CD146± endothelial progenitors (EP), CD31+CD34−CD73±CD90±CD105−CD146± mature endothelial cells, CD31−CD34−CD73±CD90+CD105−CD146+ pericytes, CD31−CD34+CD73±CD90+CD105−CD146+ transitional pericytes, and CD31−CD34+CD73highCD90+CD105−CD146− supra-adventitial-adipose stromal cells (SA-ASC). The immunophenotyping profile of SVF-MLA was dominated by a reduction of leukocytes and SA-ASC, and an increase in EP, evidencing a marked enrichment of this cell population in the course of adipose tissue microfragmentation. The role of EP in pericyte-primed MSC-mediated tissue healing, as well as the observed hormonal implication, is yet to be investigated. Full article
(This article belongs to the Special Issue Stem Cells Application in Clinical Practice: Advances and Challenges)
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