scholarly journals Muscle-on-chip: An in vitro model for donor–host cardiomyocyte coupling

2016 ◽  
Vol 212 (4) ◽  
pp. 371-373 ◽  
Author(s):  
Pieterjan Dierickx ◽  
Linda W. Van Laake

A key aspect of cardiac cell–based therapy is the proper integration of newly formed cardiomyocytes into the remnant myocardium after injury. In this issue, Aratyn-Schaus et al. (2016. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201508026) describe an in vitro model for heterogeneous cardiomyocyte coupling in which force transmission between cells can be measured.

2016 ◽  
Vol 212 (4) ◽  
pp. 389-397 ◽  
Author(s):  
Yvonne Aratyn-Schaus ◽  
Francesco S. Pasqualini ◽  
Hongyan Yuan ◽  
Megan L. McCain ◽  
George J.C. Ye ◽  
...  

The efficacy of cardiac cell therapy depends on the integration of existing and newly formed cardiomyocytes. Here, we developed a minimal in vitro model of this interface by engineering two cell microtissues (μtissues) containing mouse cardiomyocytes, representing spared myocardium after injury, and cardiomyocytes generated from embryonic and induced pluripotent stem cells, to model newly formed cells. We demonstrated that weaker stem cell–derived myocytes coupled with stronger myocytes to support synchronous contraction, but this arrangement required focal adhesion-like structures near the cell–cell junction that degrade force transmission between cells. Moreover, we developed a computational model of μtissue mechanics to demonstrate that a reduction in isometric tension is sufficient to impair force transmission across the cell–cell boundary. Together, our in vitro and in silico results suggest that mechanotransductive mechanisms may contribute to the modest functional benefits observed in cell-therapy studies by regulating the amount of contractile force effectively transmitted at the junction between newly formed and spared myocytes.


Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 1087 ◽  
Author(s):  
Bonafede ◽  
Brandi ◽  
Manfredi ◽  
Scambi ◽  
Schiaffino ◽  
...  

Stem cell therapy represents a promising approach in the treatment of several neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS). The beneficial effect of stem cells is exerted by paracrine mediators, as exosomes, suggesting a possible potential use of these extracellular vesicles as non-cell based therapy. We demonstrated that exosomes isolated from adipose stem cells (ASC) display a neuroprotective role in an in vitro model of ALS. Moreover, the internalization of ASC-exosomes by the cells was shown and the molecules and the mechanisms by which exosomes could exert their beneficial effect were addressed. We performed for the first time a comprehensive proteomic analysis of exosomes derived from murine ASC. We identified a total of 189 proteins and the shotgun proteomics analysis revealed that the exosomal proteins are mainly involved in cell adhesion and negative regulation of the apoptotic process. We correlated the protein content to the anti-apoptotic effect of exosomes observing a downregulation of pro-apoptotic proteins Bax and cleaved caspase-3 and upregulation of anti-apoptotic protein Bcl-2 α, in an in vitro model of ALS after cell treatment with exosomes. Overall, this study shows the neuroprotective effect of ASC-exosomes after their internalization and their global protein profile, that could be useful to understand how exosomes act, demonstrating that they can be employed as therapy in neurodegenerative diseases.


2020 ◽  
Author(s):  
Saúl Pérez-Castrillo ◽  
María Luisa González-Fernández ◽  
Jessica Álvarez-Suárez ◽  
Jaime Sánchez-Lázaro ◽  
Marta Esteban-Blanco ◽  
...  

Abstract Introduction: Osteoarthritis (OA) is a degenerative joint disease which affects the whole joint structure. Many authors have focused on the factors responsible for the development of inflammatory processes involved in OA. Adipose tissue-derived mesenchymal stem cells (ASCs) represent a promising alternative of cell-based therapy strategy in the treatment of OA which could be combined with any other drug. Chondroitin sulfate plays a protective role in the joint based on the decrease of pro-inflammatory cytokines, thus having an important role in activating and inhibiting the metabolic pathways in chondrocytes. Aims: The effectiveness of chondroitin sulfate and ASCs combined in an in vitro model of OA has been evaluated in this study. Materials: Cytokines and factors which are involved in OA as well as specific cartilage gene expression after adding ASCs and chondroitin sulfate have been discussed in detail. Results: Our results show a decrease in the expression of all genes related to the pro-inflammatory cytokines analysed. Although there was no increase in the expression of the specific genes of the cartilage matrix, such as collagen type II and aggrecan. Conclusions: This study shows the effectiveness of association of ASCs and chondroitin sulfate for the treatment of OA.


2016 ◽  
Vol 213 (3) ◽  
pp. 2133OIA11
Author(s):  
Yvonne Aratyn-Schaus ◽  
Francesco S. Pasqualini ◽  
Hongyan Yuan ◽  
Megan L. McCain ◽  
George J.C. Ye ◽  
...  

2016 ◽  
Vol 147 (3) ◽  
pp. 1473OIA17
Author(s):  
Yvonne Aratyn-Schaus ◽  
Francesco S. Pasqualini ◽  
Hongyan Yuan ◽  
Megan L. McCain ◽  
George J.C. Ye ◽  
...  

Lab on a Chip ◽  
2016 ◽  
Vol 16 (22) ◽  
pp. 4319-4325 ◽  
Author(s):  
Rahim Rahimi ◽  
Su Su Htwe ◽  
Manuel Ochoa ◽  
Amy Donaldson ◽  
Michael Zieger ◽  
...  

We present the use of direct-patterned laser-treated hydrophobic paper as an effective semi-permeable membrane, ideal for air–liquid interface cell culture.


2021 ◽  
Author(s):  
Julia Rogal ◽  
Raylin Xu ◽  
Julia Roosz ◽  
Claudia Teufel ◽  
Madalena Cipriano ◽  
...  

Obesity and associated diseases, such as diabetes, have reached epidemic proportions globally. In the era of 'diabesity' and due to its central role for metabolic and endocrine processes, adipose tissue (specifically white adipose tissue; WAT) has become a target of high interest for therapeutic strategies. To gain insights in cellular and molecular mechanisms of adipose (patho-)physiology, researchers traditionally relied on animal models since in vitro studies on human WAT are challenging due to the large size, buoyancy, and fragility of mature white adipocytes. Leveraging the Organ-on-Chip technology, we introduce a next-generation microphysiological in vitro model of human WAT based on a tailored microfluidic platform featuring vasculature-like perfusion. The platform integrates a 3D tissue comprising all major WAT-associated cellular components in an autologous manner, including not only mature adipocytes but also organotypic endothelial barriers and stromovascular cells featuring tissue-resident innate immune cells, specifically adipose tissue macrophages. This microphysiological tissue model recapitulates pivotal WAT functions, such as energy storage and mobilization as well as endocrine and immunomodulatory activities. The combination of all individual cell types with extra cellular matrix-like hydrogels in a precisely controllable bottom-up approach enables the generation of a multitude of replicates from the same donors circumventing issues of inter-donor variability and paving the way for personalized medicine. Moreover, it allows to adjust the model's degree of complexity to fit a specific purpose via a flexible mix-and-match approach with different cell component modules. This novel WAT-on-chip system constitutes a human- based, autologous and immunocompetent in vitro model of adipose tissue that recapitulates almost full tissue heterogeneity. In the future, the new WAT-on-chip model can become a powerful tool for human-relevant research in the field of metabolism and its associated diseases as well as for compound testing and personalized- and precision medicine applications.


Author(s):  
Hoda Keshmiri Neghab ◽  
Mohammad Hasan Soheilifar ◽  
Gholamreza Esmaeeli Djavid

Abstract. Wound healing consists of a series of highly orderly overlapping processes characterized by hemostasis, inflammation, proliferation, and remodeling. Prolongation or interruption in each phase can lead to delayed wound healing or a non-healing chronic wound. Vitamin A is a crucial nutrient that is most beneficial for the health of the skin. The present study was undertaken to determine the effect of vitamin A on regeneration, angiogenesis, and inflammation characteristics in an in vitro model system during wound healing. For this purpose, mouse skin normal fibroblast (L929), human umbilical vein endothelial cell (HUVEC), and monocyte/macrophage-like cell line (RAW 264.7) were considered to evaluate proliferation, angiogenesis, and anti-inflammatory responses, respectively. Vitamin A (0.1–5 μM) increased cellular proliferation of L929 and HUVEC (p < 0.05). Similarly, it stimulated angiogenesis by promoting endothelial cell migration up to approximately 4 fold and interestingly tube formation up to 8.5 fold (p < 0.01). Furthermore, vitamin A treatment was shown to decrease the level of nitric oxide production in a dose-dependent effect (p < 0.05), exhibiting the anti-inflammatory property of vitamin A in accelerating wound healing. These results may reveal the therapeutic potential of vitamin A in diabetic wound healing by stimulating regeneration, angiogenesis, and anti-inflammation responses.


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