scholarly journals Mesenchymal stromal cells: a novel therapy for the treatment of chronic obstructive pulmonary disease?

Thorax ◽  
2018 ◽  
Vol 73 (6) ◽  
pp. 565-574 ◽  
Author(s):  
Winifred Broekman ◽  
Padmini P S J Khedoe ◽  
Koen Schepers ◽  
Helene Roelofs ◽  
Jan Stolk ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Animal Studies ◽  
Chronic Obstructive ◽  
Tissue Destruction ◽  
Novel Therapy ◽  
Model Studies

COPD is characterised by tissue destruction and inflammation. Given the lack of curative treatments and the progressive nature of the disease, new treatments for COPD are highly relevant. In vitro cell culture and animal studies have demonstrated that mesenchymal stromal cells (MSCs) have the capacity to modify immune responses and to enhance tissue repair. These properties of MSCs provided a rationale to investigate their potential for treatment of a variety of diseases, including COPD. Preclinical models support the hypothesis that MSCs may have clinical efficacy in COPD. However, although clinical trials have demonstrated the safety of MSC treatment, thus far they have not provided evidence for MSC efficacy in the treatment of COPD. In this review, we discuss the rationale for MSC-based cell therapy in COPD, the main findings from in vitro and in vivo preclinical COPD model studies, clinical trials in patients with COPD and directions for further research.

scholarly journals Mesenchymal Stromal Cells From Emphysematous Donors and Their Extracellular Vesicles Are Unable to Reverse Cardiorespiratory Dysfunction in Experimental Severe Emphysema

2021 ◽  
Vol 9 ◽  
Author(s):  
Mariana A. Antunes ◽  
Cassia L. Braga ◽  
Tainá B. Oliveira ◽  
Jamil Z. Kitoko ◽  
Ligia L. Castro ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Therapeutic Potential ◽  
Chronic Obstructive ◽  
Severe Emphysema ◽  
Arginase 1 ◽  
The Impact

Although bone marrow-derived mesenchymal stromal cells (BM-MSCs) from patients with chronic obstructive pulmonary disease (COPD) appear to be phenotypically and functionally similar to BM-MSCs from healthy sources in vitro, the impact of COPD on MSC metabolism and mitochondrial function has not been evaluated. In this study, we aimed to comparatively characterize MSCs from healthy and emphysematous donors (H-MSCs and E-MSCs) in vitro and to assess the therapeutic potential of these MSCs and their extracellular vesicles (H-EVs and E-EVs) in an in vivo model of severe emphysema. For this purpose, C57BL/6 mice received intratracheal porcine pancreatic elastase once weekly for 4 weeks to induce emphysema; control animals received saline under the same protocol. Twenty-four hours after the last instillation, animals received saline, H-MSCs, E-MSCs, H-EVs, or E-EVs intravenously. In vitro characterization demonstrated that E-MSCs present downregulation of anti-inflammatory (TSG-6, VEGF, TGF-β, and HGF) and anti-oxidant (CAT, SOD, Nrf2, and GSH) genes, and their EVs had larger median diameter and lower average concentration. Compared with H-MSC, E-MSC mitochondria also exhibited a higher respiration rate, were morphologically elongated, expressed less dynamin-related protein-1, and produced more superoxide. When co-cultured with alveolar macrophages, both H-MSCs and E-MSCs induced an increase in iNOS and arginase-1 levels, but only H-MSCs and their EVs were able to enhance IL-10 levels. In vivo, emphysematous mice treated with E-MSCs or E-EVs demonstrated no amelioration in cardiorespiratory dysfunction. On the other hand, H-EVs, but not H-MSCs, were able to reduce the neutrophil count, the mean linear intercept, and IL-1β and TGF-β levels in lung tissue, as well as reduce pulmonary arterial hypertension and increase the right ventricular area in a murine model of elastase-induced severe emphysema. In conclusion, E-MSCs and E-EVs were unable to reverse cardiorespiratory dysfunction, whereas H-EVs administration was associated with a reduction in cardiovascular and respiratory damage in experimental severe emphysema.

scholarly journals Cell therapy for bone fracture repair: A comparative preclinical review of mesenchymal stromal cells from bone marrow and from adipose tissue

2015 ◽  
Vol 1 (2) ◽  
pp. 12 ◽  
Author(s):  
Sabrina Ena ◽  
Julia Ino ◽  
Aurelie Neirinck ◽  
Sandra Pietri ◽  
Anna Tury ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Clinical Trials ◽  
Adipose Tissue ◽  
Mesenchymal Stromal Cells ◽  
Bone Fracture ◽  
Stromal Cells ◽  
Bone Repair ◽  
Fracture Repair

Over the last decade, there has been an increasing interest among researchers for human mesenchymal stromal cells (MSC). Their regenerative properties, multilineage differentiation capacity and immunomodulatory properties make them promising candidates for treatment in various conditions. Emerging biotechnology companies specialized in cellular and regenerative therapies have been focusing their interest on MSC-based therapies, and their use in clinical trials has steadily increased. Notably, MSC are currently tested in clinical trials addressing unmet medical needs in the field of bone fracture repair and more specifically in non-union and delayed union fractures where the bone repair process is impaired. Although MSC can be isolated from various tissues, the most commonly studied sources are bone marrow (BM) and adipose tissue (Ad). In this article, we reviewed the literature directly comparing BM- and Ad-MSC for their in vitro characteristics and in vivo osteogenic potential to determine which source of MSC would be more appropriate for bone fracture repair. As considerable variations in experimental settings between studies were found, our review was based on studies meeting specific sets of criteria, notably regarding donors’ age and gender. This review of side-by-side comparisons suggests that while BM-and Ad-MSC share common general characteristics, BM-MSC have a higher intrinsic osteogenic capacity in vitro and bone repair potential in vivo.

Modulation of Matrix Metalloproteinases by Plant-Derived Products

2020 ◽  
Vol 20 ◽  
Author(s):  
Nur Najmi Mohamad Anuar ◽  
Nurul Iman Natasya Zulkafali ◽  
Azizah Ugusman
Keyword(s):  
Clinical Trials ◽  
Natural Products ◽  
Matrix Metalloproteinases ◽  
Animal Studies ◽  
Current Knowledge ◽  
In Vitro Models ◽  
In Vivo Studies ◽  
Extracellular Matrix Components

: Matrix metalloproteinases (MMPs) are a group of zinc-dependent metallo-endopeptidase that are responsible towards the degradation, repair and remodelling of extracellular matrix components. MMPs play an important role in maintaining a normal physiological function and preventing diseases such as cancer and cardiovascular diseases. Natural products derived from plants have been used as traditional medicine for centuries. Its active compounds, such as catechin, resveratrol and quercetin, are suggested to play an important role as MMPs inhibitors, thereby opening new insights into their applications in many fields, such as pharmaceutical, cosmetic and food industries. This review summarises the current knowledge on plant-derived natural products with MMP-modulating activities. Most of the reviewed plant-derived products exhibit an inhibitory activity on MMPs. Amongst MMPs, MMP-2 and MMP-9 are the most studied. The expression of MMPs is inhibited through respective signalling pathways, such as MAPK, NF-κB and PI3 kinase pathways, which contribute to the reduction in cancer cell behaviours, such as proliferation and migration. Most studies have employed in vitro models, but a limited number of animal studies and clinical trials have been conducted. Even though plant-derived products show promising results in modulating MMPs, more in vivo studies and clinical trials are needed to support their therapeutic applications in the future.

scholarly journals Evaluation of Browning Agents on the White Adipogenesis of Bone Marrow Mesenchymal Stromal Cells: A Contribution to Fighting Obesity

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 403
Author(s):  
Girolamo Di Maio ◽  
Nicola Alessio ◽  
Ibrahim Halil Demirsoy ◽  
Gianfranco Peluso ◽  
Silverio Perrotta ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
White Adipocyte ◽  
Drug Candidates ◽  
Fat Depots ◽  
Treatment Of Obesity ◽  
White Fat

Brown-like adipocytes can be induced in white fat depots by a different environmental or drug stimuli, known as “browning” or “beiging”. These brite adipocytes express thermogenin UCP1 protein and show different metabolic advantages, such as the ability to acquire a thermogenic phenotype corresponding to standard brown adipocytes that counteracts obesity. In this research, we evaluated the effects of several browning agents during white adipocyte differentiation of bone marrow-derived mesenchymal stromal cells (MSCs). Our in vitro findings identified two compounds that may warrant further in vivo investigation as possible anti-obesity drugs. We found that rosiglitazone and sildenafil are the most promising drug candidates for a browning treatment of obesity. These drugs are already available on the market for treating diabetes and erectile dysfunction, respectively. Thus, their off-label use may be contemplated, but it must be emphasized that some severe side effects are associated with use of these drugs.

scholarly journals Effect of extracorporeal shock wave therapy on equine umbilical cord blood mesenchymal stromal cells in vitro

2020 ◽  
Author(s):  
Ramés Salcedo-Jiménez ◽  
Judith Koenig ◽  
Olivia Lee ◽  
Thomas W.G. Gibson ◽  
Pavneesh Madan ◽  
...  
Keyword(s):  
Shock Wave ◽  
Mesenchymal Stromal Cells ◽  
Umbilical Cord Blood ◽  
Stromal Cells ◽  
Extracorporeal Shock Wave Therapy ◽  
Shock Wave Therapy ◽  
Extracorporeal Shock Wave ◽  
Immunomodulatory Properties

AbstractExtracorporeal shock wave therapy (ESWT) has been shown to induce different biological effects on a variety of cells, including regulation and stimulation of their function and metabolism. ESWT can promote different biological responses such as proliferation, migration, and regenerations of cells. Recent studies have shown that mesenchymal stromal cells (MSCs) secrete factors that enhance the regeneration of tissues, stimulate proliferation and differentiation of cells and decrease inflammatory and immune-reactions. Clinically, the combination of these two therapies has been used as a treatment for tendon and ligament lesions in horses; however, there is no scientific evidence supporting this combination of therapies in vivo. Therefore, the objectives of the study were to evaluate the effects of ESWT on equine umbilical cord blood mesenchymal stromal cells (CB-MSCs) proliferative, metabolic, migrative, differentiation, and immunomodulatory properties in vitro. Three equine CB-MSC cultures from independent donors were treated using an electrohydraulic shock wave generator attached to a water bath. All experiments were performed as triplicates. Proliferation, viability, migration and immunomodulatory properties of the cells were evaluated. Equine CB-MSCs were induced to evaluate their trilineage differentiation potential. ESWT treated cells had increased metabolic activity, showed positive adipogenic, osteogenic, and chondrogenic differentiation, and showed higher potential for differentiation towards the adipogenic and osteogenic cell fates. ESWT treated cells showed similar immunomodulatory properties to none-ESWT treated cells. Equine CB-MSCs are responsive to ESWT treatment and showed increased metabolic, adipogenic and osteogenic activity, but unaltered immunosuppressive properties. In vivo studies are warranted to determine if synergistic effects occur in the treatment of musculoskeletal injuries if ESWT and equine CB-MSC therapies are combined.

Influence of particulate and dissociated metal-on-metal hip endoprosthesis wear on mesenchymal stromal cells in vivo and in vitro

Biomaterials ◽  
2016 ◽  
Vol 98 ◽  
pp. 31-40 ◽  
Author(s):  
Anastasia Rakow ◽  
Janosch Schoon ◽  
Anke Dienelt ◽  
Thilo John ◽  
Martin Textor ◽  
...  
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Hip Endoprosthesis ◽  
Metal On Metal
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