Adipose-Derived Mesenchymal Stem Cells, Cell-Based Therapies, and Biomaterials as New Regenerative Strategies

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 October 2021) | Viewed by 29221

Special Issue Editor


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Guest Editor
Associate Professor of Plastic and Reconstructive Surgery, Surgical Science Department, University of Rome “Tor Vergata”, Rome, Italy
Interests: regenerative plastic surgery; adipose-derived mesenchymal stem cells; fat grafting; platelet-rich plasma; growth factors; mesenchymal stem cells; biomaterials; hair loss; androgenetic alopecia
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Special Issue Information

Dear Colleagues,

Adipose-derived mesenchymal stem cells (AD-MSCs), cell-based therapies, and biomaterials are interrelated terms that often go hand in hand when discussing strategies to improve tissue regeneration or to repair tissue defects. In particular, stem cells (mesenchymal and follicular), biotechnology and bioactive molecules (platelet-rich plasma (PRP), micrografts), and biomaterials (mesh, scaffolds, hydrogels) may be helpful in this field.

In light of current knowledge on mesenchymal stem cells (MSCs), AD-MSCs, epithelial and dermal cells, human follicle mesenchymal stem cells (HF-MSCs), and biomaterials such as titanium/polypropylene mesh, numerous researchers have developed different strategies to improve the effects of these varied biotechnology applications.

This Special Issue aims to collect multidisciplinary submissions of original research articles that demonstrate basic research and clinical impacts of MSCs, AD-MSCs, PRP, micrografts, and biomaterials in tissue repair. Review articles that describe the current state of the art are also welcomed.

Potential topics include but are not limited to:

  • The molecular mechanisms of MSCs during regeneration;
  • Therapeutic application of MSCs for major diseases and clinical conditions such as regenerative plastic surgery;
  • MSCs and engineered MSCs as vehicles for drug delivery;
  • Therapeutic application of biomaterials (titanium/polypropylene mesh, scaffolds, hydrogel, colloids) for major diseases (outcomes of breast cancer, mastectomy, ulcers, loss of substances) and additional clinical conditions;
  • Skin biostimulation with biomaterials/PRP/stem cells/microneedling;
  • The new emergent potential use of AD-MSCs in COVID-19 treatment.

Dr. Pietro Gentile
Guest Editor

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Keywords

  • adipose-derived stem cells
  • cell-based therapies
  • fat grafting
  • platelet-rich plasma
  • biomaterials
  • soft tissue defects
  • ulcers
  • breast
  • mastectomy
  • COVID-19

Published Papers (10 papers)

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Editorial

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2 pages, 181 KiB  
Editorial
Adipose-Derived Mesenchymal Stem Cells, Cell-Based Therapies, and Biomaterials as New Regenerative Strategies in Plastic Surgery
by Pietro Gentile
Biomedicines 2022, 10(8), 1875; https://doi.org/10.3390/biomedicines10081875 - 4 Aug 2022
Viewed by 1157
Abstract
Adipose-derived mesenchymal stem cells (AD-MSCs), cell-based therapies, and biomaterials are interrelated terms that often go hand in hand when discussing strategies to improve tissue regeneration or to repair tissue defects [...] Full article

Research

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20 pages, 4111 KiB  
Article
MicroRNA-Enriched Exosomes from Different Sources of Mesenchymal Stem Cells Can Differentially Modulate Functions of Immune Cells and Neurogenesis
by Naina Soni, Suchi Gupta, Surender Rawat, Vishnu Krishnakumar, Sujata Mohanty and Arup Banerjee
Biomedicines 2022, 10(1), 69; https://doi.org/10.3390/biomedicines10010069 - 30 Dec 2021
Cited by 14 | Viewed by 3268
Abstract
Adult Mesenchymal stem cells-derived exosomes carry several biologically active molecules that play prominent roles in controlling disease manifestations. The content of these exosomes, their functions, and effect on the immune cells may differ depending on their tissue sources. Therefore, in this study, we [...] Read more.
Adult Mesenchymal stem cells-derived exosomes carry several biologically active molecules that play prominent roles in controlling disease manifestations. The content of these exosomes, their functions, and effect on the immune cells may differ depending on their tissue sources. Therefore, in this study, we purified the exosomes from three different sources and, using the RNA-Seq approach, highly abundant microRNAs were identified and compared between exosomes and parental cells. The effects of exosomes on different immune cells were studied in vitro by incubating exosomes with PBMC and neutrophils and assessing their functions. The expression levels of several miRNAs varied within the different MSCs and exosomes. Additionally, the expression profile of most of the miRNAs was not similar to that of their respective sources. Exosomes isolated from different sources had different abilities to induce the process of neurogenesis and angiogenesis. Moreover, these exosomes demonstrated their varying effect on PBMC proliferation, neutrophil survival, and NET formation, highlighting their versatility and broad interaction with immune cells. The knowledge gained from this study will improve our understanding of the miRNA landscape of exosomes from hMSCs and provide a resource for further improving our understanding of exosome cargo and their interaction with immune cells. Full article
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14 pages, 2392 KiB  
Article
Enhanced Extracellular Matrix Deposition on Titanium Implant Surfaces: Cellular and Molecular Evidences
by Guya Diletta Marconi, Luigia Fonticoli, Ylenia Della Rocca, Stefano Oliva, Thangavelu Soundara Rajan, Oriana Trubiani, Giovanna Murmura, Francesca Diomede and Jacopo Pizzicannella
Biomedicines 2021, 9(11), 1710; https://doi.org/10.3390/biomedicines9111710 - 18 Nov 2021
Cited by 16 | Viewed by 2035
Abstract
The surface structure of the titanium dental implants can modulate the activity of mesenchymal stem cells in order to promote the upregulation of osteoblastic related genes and the release of extracellular matrix (ECM) components. The present work was focused on the in vitro [...] Read more.
The surface structure of the titanium dental implants can modulate the activity of mesenchymal stem cells in order to promote the upregulation of osteoblastic related genes and the release of extracellular matrix (ECM) components. The present work was focused on the in vitro evaluation of the interaction of human periodontal ligament stem cells (hPDLSCs) and two different implant titanium surfaces topography (CTRL and TEST). This study was aimed at analyzing the cytotoxicity of the dental implant surfaces, the cellular adhesion capacity, and the improvement in the release of ECM molecules in an in vitro model. These parameters were carried out by means of the microscopic evaluation, viability assays, immunofluorescence, Western blot and RT-PCR investigations. The knowledge of the cell/implant interaction is essential for implant healing in order to obtain a more performing surfaces that promote the ECM release and provide the starting point to initiate the osseointegration process. Full article
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15 pages, 1967 KiB  
Article
A Novel Cellular Therapy to Treat Pancreatic Pain in Experimental Chronic Pancreatitis Using Human Alpha-1 Antitrypsin Overexpressing Mesenchymal Stromal Cells
by Rebecca P. Chow, Kevin Nguyen, Wenyu Gou, Erica Green, Katherine Morgan, William Lancaster, Kristi Helke, Charlie Strange and Hongjun Wang
Biomedicines 2021, 9(11), 1695; https://doi.org/10.3390/biomedicines9111695 - 16 Nov 2021
Cited by 4 | Viewed by 2716
Abstract
Chronic pancreatitis (CP) is characterized by pancreatic inflammation, fibrosis, and abdominal pain that is challenging to treat. Mesenchymal stromal cells (MSCs) overexpressing human alpha-1 antitrypsin (hAAT-MSCs) showed improved mobility and protective functions over native MSCs in nonobese diabetic mice. We investigated whether hAAT-MSCs [...] Read more.
Chronic pancreatitis (CP) is characterized by pancreatic inflammation, fibrosis, and abdominal pain that is challenging to treat. Mesenchymal stromal cells (MSCs) overexpressing human alpha-1 antitrypsin (hAAT-MSCs) showed improved mobility and protective functions over native MSCs in nonobese diabetic mice. We investigated whether hAAT-MSCs could mitigate CP and its associated pain using trinitrobenzene sulfonic acid (TNBS)-induced CP mouse models. CP mice were given native human MSCs or hAAT-MSCs (0.5 × 106 cells/mouse, i.v., n = 6–8/group). The index of visceral pain was measured by graduated von Frey filaments. Pancreatic morphology and pancreatic mast cell count were analyzed by morphological stains. Nociceptor transient receptor potential vanilloid 1 (TRPV1) expression in dorsal root ganglia (DRG) was determined by immunohistochemistry. hAAT-MSC-treated CP mice best preserved pancreatic morphology and histology. MSC or hAAT-MSC infusion reduced abdominal pain sensitivities. hAAT-MSC therapy also suppressed TRPV1 expression in DRG and reduced pancreatic mast cell density induced by TNBS. Overall, hAAT-MSCs reduced pain and mitigated pancreatic inflammation in CP equal to MSCs with a trend toward a higher pancreatic weight and better pain relief in the hAAT-MSC group compared to the MSC group. Both MSCs and hAAT-MSCs might be used as a novel therapeutic tool for CP-related pain. Full article
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12 pages, 3191 KiB  
Article
Comparison of the Confluence-Initiated Neurogenic Differentiation Tendency of Adipose-Derived and Bone Marrow-Derived Mesenchymal Stem Cells
by Szu-Hsien Wu, Yu-Ting Liao, Chi-Han Huang, Yi-Chou Chen, En-Rung Chiang and Jung-Pan Wang
Biomedicines 2021, 9(11), 1503; https://doi.org/10.3390/biomedicines9111503 - 20 Oct 2021
Cited by 7 | Viewed by 2152
Abstract
Adipose-derived mesenchymal stem cells (ADSCs), which tended to neurogenically differentiate spontaneously after achieving high confluence, were observed. Human ADSCs reaching 80% confluence were cultured in DMEM without an inducing factor for 24 h and then maintained in DMEM plus 1% FBS medium for [...] Read more.
Adipose-derived mesenchymal stem cells (ADSCs), which tended to neurogenically differentiate spontaneously after achieving high confluence, were observed. Human ADSCs reaching 80% confluence were cultured in DMEM without an inducing factor for 24 h and then maintained in DMEM plus 1% FBS medium for 7 days. The neurogenic, adipogenic, and osteogenic genes of the factor-induced and confluence-initiated differentiation of the ADSCs and bone marrow-derived mesenchymal stem cells (BMSCs) at passages 3 to 5 were determined and compared using RT-qPCR, and the neurogenic differentiation was confirmed using immunofluorescent staining. In vitro tests revealed that the RNA and protein expression of neuronal markers, including class III β-tubulin (TUBB3), microtubule-associated protein 2 (MAP2), neurofilament medium polypeptide (NEFM), neurofilament heavy polypeptide (NEFH), and neurofilament light polypeptide (NEFL), had been enhanced in the confluence-initiated differentiation of the ADSCs. In addition, the expressions of neurotrophins, such as the nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and glial cell-derived neurotrophic factor (GDNF), were also elevated in the confluence-initiated differentiation of the ADSCs. However, the confluent ADSCs did not show a tendency toward spontaneous adipogenic and osteogenic differentiation. Moreover, compared with the confluent ADSCs, the tendency of spontaneous neurogenic, adipogenic, and osteogenic differentiation of the confluent human bone marrow mesenchymal stem cells (BMSCs) was not observed. The results indicated that ADSCs had the potential to spontaneously differentiate into neuron-like cells during the confluent culture period; however, this tendency was not observed in BMSCs. Full article
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19 pages, 7255 KiB  
Article
Differentiation Behaviour of Adipose-Derived Stromal Cells (ASCs) Seeded on Polyurethane-Fibrin Scaffolds In Vitro and In Vivo
by Katrin Radeloff, Dorothee Weiss, Rudolf Hagen, Norbert Kleinsasser and Andreas Radeloff
Biomedicines 2021, 9(8), 982; https://doi.org/10.3390/biomedicines9080982 - 9 Aug 2021
Cited by 6 | Viewed by 1880
Abstract
Adipose-derived stromal cells (ASCs) are a promising cell source for tissue engineering and regenerative medicine approaches for cartilage replacement. For chondrogenic differentiation, human (h)ASCs were seeded on three-dimensional polyurethane (PU) fibrin composites and induced with a chondrogenic differentiation medium containing TGF-ß3, BMP-6, and [...] Read more.
Adipose-derived stromal cells (ASCs) are a promising cell source for tissue engineering and regenerative medicine approaches for cartilage replacement. For chondrogenic differentiation, human (h)ASCs were seeded on three-dimensional polyurethane (PU) fibrin composites and induced with a chondrogenic differentiation medium containing TGF-ß3, BMP-6, and IGF-1 in various combinations. In addition, in vitro predifferentiated cell-seeded constructs were implanted into auricular cartilage defects of New Zealand White Rabbits for 4 and 12 weeks. Histological, immunohistochemical, and RT-PCR analyses were performed on the constructs maintained in vitro to determine extracellular matrix (ECM) deposition and expression of specific cartilage markers. Chondrogenic differentiated constructs showed a uniform distribution of cells and ECM proteins. RT-PCR showed increased gene expression of collagen II, collagen X, and aggrecan and nearly stable expression of SOX-9 and collagen I. Rabbit (r)ASC-seeded PU-fibrin composites implanted in ear cartilage defects of New Zealand White Rabbits showed deposition of ECM with structures resembling cartilage lacunae by Alcian blue staining. However, extracellular calcium deposition became detectable over the course of 12 weeks. RT-PCR showed evidence of endochondral ossification during the time course with the expression of specific marker genes (collagen X and RUNX-2). In conclusion, hASCs show chondrogenic differentiation capacity in vitro with the expression of specific marker genes and deposition of cartilage-specific ECM proteins. After implantation of predifferentiated rASC-seeded PU-fibrin scaffolds into a cartilage defect, the constructs undergo the route of endochondral ossification. Full article
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19 pages, 4843 KiB  
Article
Simvastatin Enhances the Chondrogenesis But Not the Osteogenesis of Adipose-Derived Stem Cells in a Hyaluronan Microenvironment
by Shun-Cheng Wu, Chih-Hsiang Chang, Ling-Hua Chang, Che-Wei Wu, Jhen-Wei Chen, Chung-Hwan Chen, Yi-Shan Lin, Je-Ken Chang and Mei-Ling Ho
Biomedicines 2021, 9(5), 559; https://doi.org/10.3390/biomedicines9050559 - 17 May 2021
Cited by 7 | Viewed by 2925
Abstract
Directing adipose-derived stem cells (ADSCs) toward chondrogenesis is critical for ADSC-based articular cartilage regeneration. Simvastatin (SIM) was reported to promote both chondrogenic and osteogenic differentiation of ADSCs by upregulating bone morphogenetic protein-2 (BMP-2). We previously found that ADSC chondrogenesis is initiated and promoted [...] Read more.
Directing adipose-derived stem cells (ADSCs) toward chondrogenesis is critical for ADSC-based articular cartilage regeneration. Simvastatin (SIM) was reported to promote both chondrogenic and osteogenic differentiation of ADSCs by upregulating bone morphogenetic protein-2 (BMP-2). We previously found that ADSC chondrogenesis is initiated and promoted in a hyaluronan (HA) microenvironment (HAM). Here, we further hypothesized that SIM augments HAM-induced chondrogenesis but not osteogenesis of ADSCs. ADSCs were treated with SIM in a HAM (SIM plus HAM) by HA-coated wells or HA-enriched fibrin (HA/Fibrin) hydrogel, and chondrogenic differentiation of ADSCs was evaluated. SIM plus HAM increased chondrogenesis more than HAM or SIM alone, including cell aggregation, chondrogenic gene expression (collagen type II and aggrecan) and cartilaginous tissue formation (collagen type II and sulfated glycosaminoglycan). In contrast, SIM-induced osteogenesis in ADSCs was reduced in SIM plus HAM, including mRNA expression of osteogenic genes, osteocalcin and alkaline phosphatase (ALP), ALP activity and mineralization. SIM plus HAM also showed the most effective increases in the mRNA expression of BMP-2 and transcription factors of SOX-9 and RUNX-2 in ADSCs, while these effects were reversed by CD44 blockade. HAM suppressed the levels of JNK, p-JNK, P38 and p-P38 in ADSCs, and SIM plus HAM also decreased SIM-induced phosphorylated JNK and p38 levels. In addition, SIM enhanced articular cartilage regeneration, as demonstrated by implantation of an ADSCs/HA/Fibrin construct in an ex vivo porcine articular chondral defect model. The results from this study indicate that SIM may be an enhancer of HAM-initiated MSC-based chondrogenesis and avoid osteogenesis. Full article
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Review

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30 pages, 911 KiB  
Review
Cell and Cell Free Therapies in Osteoarthritis
by Pau Peláez, Elena Damiá, Marta Torres-Torrillas, Deborah Chicharro, Belén Cuervo, Laura Miguel, Ayla del Romero, Jose Maria Carrillo, Joaquín J. Sopena and Mónica Rubio
Biomedicines 2021, 9(11), 1726; https://doi.org/10.3390/biomedicines9111726 - 19 Nov 2021
Cited by 12 | Viewed by 3977
Abstract
Osteoarthritis (OA) is the most common articular disease in adults and has a current prevalence of 12% in the population over 65 years old. This chronic disease causes damage to articular cartilage and synovial joints, causing pain and leading to a negative impact [...] Read more.
Osteoarthritis (OA) is the most common articular disease in adults and has a current prevalence of 12% in the population over 65 years old. This chronic disease causes damage to articular cartilage and synovial joints, causing pain and leading to a negative impact on patients’ function, decreasing quality of life. There are many limitations regarding OA conventional therapies—pharmacological therapy can cause gastrointestinal, renal, and cardiac adverse effects, and some of them could even be a threat to life. On the other hand, surgical options, such as microfracture, have been used for the last 20 years, but hyaline cartilage has a limited regeneration capacity. In recent years, the interest in new therapies, such as cell-based and cell-free therapies, has been considerably increasing. The purpose of this review is to describe and compare bioregenerative therapies’ efficacy for OA, with particular emphasis on the use of mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP). In OA, these therapies might be an alternative and less invasive treatment than surgery, and a more effective option than conventional therapies. Full article
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15 pages, 3448 KiB  
Review
Adipose-Derived Stem Cell: “Treat or Trick”
by Siti Syahira Airuddin, Ahmad Sukari Halim, Wan Azman Wan Sulaiman, Ramlah Kadir and Nur Azida Mohd Nasir
Biomedicines 2021, 9(11), 1624; https://doi.org/10.3390/biomedicines9111624 - 5 Nov 2021
Cited by 12 | Viewed by 3052
Abstract
Stem cells have been widely used for treating disease due to the various benefits they offer in the curing process. Several treatments using stem cells have undergone clinical trials, such as cell-based therapies for heart disease, sickle cell disease, thalassemia, etc. Adipose-derived stem [...] Read more.
Stem cells have been widely used for treating disease due to the various benefits they offer in the curing process. Several treatments using stem cells have undergone clinical trials, such as cell-based therapies for heart disease, sickle cell disease, thalassemia, etc. Adipose-derived stem cells are some of the many mesenchymal stem cells that exist in our body that can be harvested from the abdomen, thighs, etc. Adipose tissue is easy to harvest, and its stem cells can be obtained in higher volumes compared to stem cells harvested from bone marrow, for which a more invasive technique is required with a smaller volume obtained. Many scientists have expressed interest in investigating the role of adipose-derived stem cells in treating disease since their use was first described. This is due to these stem cells’ ability to differentiate into multiple lineages and secrete a variety of growth factors and proteins. Previous studies have found that the hormones, cytokines, and growth factors contained in adipose tissue play major roles in the metabolic regulation of adipose tissue, as well as in energy balance and whole-body homeostasis through their endocrine, autocrine, and paracrine functions. These are thought to be important contributors to the process of tissue repair and regeneration. However, it remains unclear how effective and safe ADSCs are in treating diseases. The research that has been carried out to date is in order to investigate the impact of ADSCs in disease treatment, as described in this review, to highlight its “trick or treat” effect in medical treatment. Full article
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8 pages, 633 KiB  
Review
Adipose-Derived Mesenchymal Stem Cells (AD-MSCs) against Ultraviolet (UV) Radiation Effects and the Skin Photoaging
by Pietro Gentile and Simone Garcovich
Biomedicines 2021, 9(5), 532; https://doi.org/10.3390/biomedicines9050532 - 11 May 2021
Cited by 32 | Viewed by 4881
Abstract
The skin is a natural barrier against the ultraviolet (UV) radiation of sunlight. The long-term and/or repetitive exposure to the sunlight and related UV radiation may change the skin structure, decreasing collagen production, promoting premature skin aging, which is termed “photoaging”. The signs [...] Read more.
The skin is a natural barrier against the ultraviolet (UV) radiation of sunlight. The long-term and/or repetitive exposure to the sunlight and related UV radiation may change the skin structure, decreasing collagen production, promoting premature skin aging, which is termed “photoaging”. The signs of photoaging include wrinkle formation, mottled pigmentation, and/or cancerous changes. For many years, adipose-derived mesenchymal stem cells (AD-MSCs) and fat grafting (F-GRF) have been used to combat photoaging signs, wrinkles, loss of elasticity, and face soft tissue defects. Several studies have analyzed in vitro actions of AD-MSCs against photoaging’s effects, thanks to their migratory activity, paracrine actions, and related in vivo–ex vivo outcomes. In fact, AD-MSCs act against skin photoaging in vitro via activation of dermal fibroblast proliferation, antioxidant effect, and matrix metalloproteinases (MMPs) reduction. In vivo and ex vivo outcomes regard the local injection of AD-MSCs, F-GRF, and/or enriched-F-GRF with AD-MSCs directly in the wrinkles and the face’s soft tissue defects. This concise review summarizes the most recent in vitro, in vivo and ex vivo outcomes and developments on the effects of AD-MSCs and F-GRF against photoaging. Full article
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