scholarly journals Toxicity and Functional Impairment in Human Adipose Tissue-Derived Stromal Cells (hASCs) Following Long-Term Exposure to Very Small Iron Oxide Particles (VSOPs)

Nanomaterials ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 741 ◽  
Author(s):  
Katrin Radeloff ◽  
Andreas Radeloff ◽  
Mario Ramos Tirado ◽  
Agmal Scherzad ◽  
Rudolf Hagen ◽  
...  

Magnetic nanoparticles (NPs), such as very small iron oxide NPs (VSOPs) can be used for targeted drug delivery, cancer treatment or tissue engineering. Another important field of application is the labelling of mesenchymal stem cells to allow in vivo tracking and visualization of transplanted cells using magnetic resonance imaging (MRI). For these NPs, however, various toxic effects, as well as functional impairment of the exposed cells, are described. The present study evaluates the influence of VSOPs on the multilineage differentiation ability and cytokine secretion of human adipose tissue derived stromal cells (hASCs) after long-term exposure. Human ASCs were labelled with VSOPs, and the efficacy of the labelling was documented over 4 weeks in vitro cultivation of the labelled cells. Unlabelled hASCs served as negative controls. Four weeks after labelling, adipogenic and osteogenic differentiation was histologically evaluated and quantified by polymerase chain reaction (PCR). Changes in gene expression of IL-6, IL-8, VEGF and caspase 3 were determined over 4 weeks. Four weeks after the labelling procedure, labelled and unlabelled hASCs did not differ in the gene expression of IL-6, IL-8, VEGF and caspase 3. Furthermore, the labelling procedure had no influence on the multidifferentiation ability of hASC. The percentage of labelled cells decreased during in vitro expansion over 4 weeks. Labelling with VSOPs and long-term intracellular disposition probably have no influence on the physiological functions of hASCs. This could be important for the future in vivo use of iron oxide NPs.

Endocrinology ◽  
2003 ◽  
Vol 144 (12) ◽  
pp. 5578-5584 ◽  
Author(s):  
Philippe Linscheid ◽  
Dalma Seboek ◽  
Eric S. Nylen ◽  
Igor Langer ◽  
Mirjam Schlatter ◽  
...  

PLoS ONE ◽  
2009 ◽  
Vol 4 (7) ◽  
pp. e6278 ◽  
Author(s):  
Beatrice Cousin ◽  
Emmanuel Ravet ◽  
Sandrine Poglio ◽  
Fabienne De Toni ◽  
Mélanie Bertuzzi ◽  
...  

2007 ◽  
Vol 342-343 ◽  
pp. 385-388
Author(s):  
So Eun Lee ◽  
Young Mee Jung ◽  
Soo Hyun Kim ◽  
Sang Heon Kim ◽  
Jong Won Rhie ◽  
...  

In cartilage tissue engineering, as a cell source, adult stem cells are very attractive for clinical applications. Recent studies suggest that human adipose tissue-derived stromal cells (ASCs) have multilineage potential similar to bone marrow-derived stromal cells (BMSCs). ASCs are obtained from adipose tissue easily isolated by suction-assisted lipectomy in various body parts. Also, as one of major factors of cartilage tissue engineering, scaffolds have an important role in cartilage formation. Poly(L-lactide-co-ε-carprolactone) scaffolds have physiological activity, biodegradability, high cell affinity, and mechano-activity. The object of this study is cartilaginous tissue formation using highly elastic PLCL scaffolds and ASCs in vitro and in vivo. Poly(L-lactide-co-ε-carprolactone) copolymers were synthesized from lactide and ε-carprolactone in the presence of stannous octoate as catalyst. The scaffolds with 85% porosity and 300-500μm pore size were fabricated by gel-pressing method. ASCs were seeded on scaffolds and cultured for 21days in vitro. Cell/polymer constructs were characterized by reverse transcriptase-polymerase chain reaction for confirming differentiation to chondrocytes onto PLCL scaffolds. Also, for examining cartilaginous tissue formation in vivo, ASCs seeded scaffolds which were induced chondrogenesis for 2 weeks were implanted in nude mice subcutaneously for up to 8weeks. Histological studies showed that implants partially developed cartilaginous tissue within lacunae. And there was an accumulation of sulfated glycoaminoglycans. Immunohistochemical analysis revealed that implants were positively stained for specific extracellular matrix. These results indicate that ASCs and PLCL scaffols could be used to cartilage tissue engineering.


2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Xinxing Wan ◽  
Liyong Zhu ◽  
Liling Zhao ◽  
Lin Peng ◽  
Jing Xiong ◽  
...  

AbstractThe period circadian regulator 3 (PER3) has been reported to play a negative role in human immortalized bone marrow-derived Scp-1 cells (iBMSCs) and patient adipose-derived stromal cells (PASCs) or a negative/positive role in mice adipogenesis. However, human PER3 (hPER3) was identified as a positive regulator of human adipose tissue-derived stromal cells (hADSCs) adipogenesis in this study. Silencing or overexpression of hPER3 in hADSCs inhibited and promoted adipogenesis in vitro. In vivo, the overexpression of hPER3 increased high-fat diet-induced inguinal white adipose tissue (iWAT) and epididymal white adipose tissue (eWAT) forms, increasing systemic glucose intolerance and insulin resistance. Molecularly, hPER3 does not interact with hPPARγ, but represses Notch1 signaling pathway to enhance adipogenesis by interacting with hHSP90AA1, which is able to combine with the promoter of hNotch1 and inactivate its expression. Thus, our study revealed hPER3 as a critical positive regulator of hADSCs adipogenesis, which was different from the other types of cells, providing a critical role of it in treating obesity.


Metabolites ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 59
Author(s):  
Olga Hahn ◽  
Lena-Christin Ingwersen ◽  
Abdelrahman Soliman ◽  
Mohamed Hamed ◽  
Georg Fuellen ◽  
...  

Adipose tissue plays an active role in the regulation of the body’s energy balance. Mesenchymal stem/stromal cells from adipose tissue (adMSC) are the precursor cells for repair and adipogenesis. Since the balance of the differentiation state of adipose tissue-resident cells is associated with the development of various diseases, the examination of the regulation of proliferation and differentiation of adMSC might provide new therapeutic targets. Transforming growth factor-β1 (TGF-ß1) is synthetized by many cell types and is involved in various biological processes. Here, we investigated the effects of different concentrations of TGF-ß1 (1–10 ng/mL) on adMSC proliferation, metabolic activity, and analyzed the gene expression data obtained from DNA microarrays by bioinformatics. TGF-ß1 induced the concentration- and time-dependent increase in the cell number of adMSC with simultaneously unchanged cell cycle distributions. The basal oxygen consumption rates did not change significantly after TGF-ß1 exposure. However, glycolytic activity was significantly increased. The gene expression analysis identified 3275 differentially expressed genes upon exposure to TGF-ß1. According to the pathway enrichment analyses, they also included genes associated with energy metabolism. Thus, it was shown that TGF-ß1 induces changes in the energy metabolism of adMSC. Whether these effects are of relevance in vivo and whether they contribute to pathogenesis should be addressed in further examinations.


2021 ◽  
Vol 22 (15) ◽  
pp. 7920
Author(s):  
Myroslava Mytsyk ◽  
Giulia Cerino ◽  
Gregory Reid ◽  
Laia Gili Sole ◽  
Friedrich S. Eckstein ◽  
...  

The therapeutic potential of mesenchymal stromal/stem cells (MSC) for treating cardiac ischemia strongly depends on their paracrine-mediated effects and their engraftment capacity in a hostile environment such as the infarcted myocardium. Adipose tissue-derived stromal vascular fraction (SVF) cells are a mixed population composed mainly of MSC and vascular cells, well known for their high angiogenic potential. A previous study showed that the angiogenic potential of SVF cells was further increased following their in vitro organization in an engineered tissue (patch) after perfusion-based bioreactor culture. This study aimed to investigate the possible changes in the cellular SVF composition, in vivo angiogenic potential, as well as engraftment capability upon in vitro culture in harsh hypoxia conditions. This mimics the possible delayed vascularization of the patch upon implantation in a low perfused myocardium. To this purpose, human SVF cells were seeded on a collagen sponge, cultured for 5 days in a perfusion-based bioreactor under normoxia or hypoxia (21% and <1% of oxygen tension, respectively) and subcutaneously implanted in nude rats for 3 and 28 days. Compared to ambient condition culture, hypoxic tension did not alter the SVF composition in vitro, showing similar numbers of MSC as well as endothelial and mural cells. Nevertheless, in vitro hypoxic culture significantly increased the release of vascular endothelial growth factor (p < 0.001) and the number of proliferating cells (p < 0.00001). Moreover, compared to ambient oxygen culture, exposure to hypoxia significantly enhanced the vessel length density in the engineered tissues following 28 days of implantation. The number of human cells and human proliferating cells in hypoxia-cultured constructs was also significantly increased after 3 and 28 days in vivo, compared to normoxia. These findings show that a possible in vivo delay in oxygen supply might not impair the vascularization potential of SVF- patches, which qualifies them for evaluation in a myocardial ischemia model.


Gut ◽  
2008 ◽  
Vol 58 (4) ◽  
pp. 570-581 ◽  
Author(s):  
H Aurich ◽  
M Sgodda ◽  
P Kaltwasser ◽  
M Vetter ◽  
A Weise ◽  
...  

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1378
Author(s):  
Peyton Gibler ◽  
Jeffrey Gimble ◽  
Katie Hamel ◽  
Emma Rogers ◽  
Michael Henderson ◽  
...  

Human adipose-derived stromal/stem cells (hASC) are widely used for in vitro modeling of physiologically relevant human adipose tissue. These models are useful for the development of tissue constructs for soft tissue regeneration and 3-dimensional (3D) microphysiological systems (MPS) for drug discovery. In this systematic review, we report on the current state of hASC culture and assessment methods for adipose tissue engineering using 3D MPS. Our search efforts resulted in the identification of 184 independent records, of which 27 were determined to be most relevant to the goals of the present review. Our results demonstrate a lack of consensus on methods for hASC culture and assessment for the production of physiologically relevant in vitro models of human adipose tissue. Few studies have assessed the impact of different 3D culture conditions on hASC adipogenesis. Additionally, there has been a limited use of assays for characterizing the functionality of adipose tissue in vitro. Results from this study suggest the need for more standardized culture methods and further analysis on in vitro tissue functionality. These will be necessary to validate the utility of 3D MPS as an in vitro model to reduce, refine, and replace in vivo experiments in the drug discovery regulatory process.


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