Engineering an Environment for the Study of Fibrosis: A 3D Human Muscle Model with Endothelium Specificity and Endomysium

Bersini, Simone; Gilardi, Mara; Ugolini, Giovanni Stefano; Sansoni, Veronica; Talò, Giuseppe; Perego, Silvia; Zanotti, Simona; Ostano, Paola; Mora, Marina; Soncini, Monica; Vanoni, Marco; Lombardi, Giovanni; Moretti, Matteo

doi:10.1016/j.celrep.2018.11.092

Cited by 59 publications

(73 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For focal adhesion quantification, images of paxillin-stained samples were thresholded (binary images were obtained by selecting the commands "image, adjust, threshold" in the Fiji software; the same value was set for all images referred to the same condition) and the number of paxillin foci identified through the "particle analysis" command using Fiji software. Regarding quantification of the area covered by FAK, lamin A, Nesprin-1, and YAP, images were processed using Fiji software following established protocols (Bersini et al, 2018) (region of interest selection within z-projected stacks; thresholding [binary images were obtained by selecting the commands "image, adjust, threshold"; the same value was set for all images referred to the same condition]; computation of area fraction or mean intensity value of the fluorescent signal). For invasion assay quantification, the cells were live-imaged for 24 h after cell membrane staining with a fluorescent dye.…”

Section: Image Analysis and Quantificationmentioning

confidence: 99%

Nup93 regulates breast tumor growth by modulating cell proliferation and actin cytoskeleton remodeling

et al. 2020

Self Cite

View full text Add to dashboard Cite

Nucleoporin 93 (Nup93) expression inversely correlates with the survival of triple-negative breast cancer patients. However, our knowledge of Nup93 function in breast cancer besides its role as structural component of the nuclear pore complex is not understood. Combination of functional assays and genetic analyses suggested that chromatin interaction of Nup93 partially modulates the expression of genes associated with actin cytoskeleton remodeling and epithelial to mesenchymal transition, resulting in impaired invasion of triple-negative, claudin-low breast cancer cells. Nup93 depletion induced stress fiber formation associated with reduced cell migration/proliferation and impaired expression of mesenchymal-like genes. Silencing LIMCH1, a gene responsible for actin cytoskeleton remodeling and up-regulated upon Nup93 depletion, partially restored the invasive phenotype of cancer cells. Loss of Nup93 led to significant defects in tumor establishment/propagation in vivo, whereas patient samples revealed that high Nup93 and low LIMCH1 expression correlate with late tumor stage. Our approach identified Nup93 as contributor of triple-negative, claudin-low breast cancer cell invasion and paves the way to study the role of nuclear envelope proteins during breast cancer tumorigenesis.

show abstract

Section: Image Analysis and Quantificationmentioning

confidence: 99%

Nup93 regulates breast tumor growth by modulating cell proliferation and actin cytoskeleton remodeling

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…[ 99,132 ] Interestingly, Bersini et al reported on the respecification of primary endothelial cells into muscle‐specific endothelium in their 3D human muscle model, the first study to demonstrate this phenomenon for in vitro endothelial cultures. [ 133 ] Although some studies attempt to use primary vascular endothelial cells, these cells can be heterogenous and are just starting to be characterized in adult human organs. [ 134 ] Recently, the Carmeliet group published a seminal study identifying the single‐cell transcriptional profiles of murine endothelium, demonstrating the heterogeneity in endothelial populations that may provide a key to engineering meso‐ and microscale vascular models and regenerative cues.…”

Section: Meso‐ and Microvascular Engineeringmentioning

confidence: 99%

From Arteries to Capillaries: Approaches to Engineering Human Vasculature

Fleischer

Tavakol

Vunjak-Novakovic

2020

Adv Funct Materials

111

View full text Add to dashboard Cite

From microscaled capillaries to millimeter‐sized vessels, human vasculature spans multiple scales and cell types. The convergence of bioengineering, materials science, and stem cell biology has enabled tissue engineers to recreate the structure and function of different hierarchical levels of the vascular tree. Engineering large‐scale vessels aims to replace damaged arteries, arterioles, and venules and their routine application in the clinic may become a reality in the near future. Strategies to engineer meso‐ and microvasculature are extensively explored to generate models for studying vascular biology, drug transport, and disease progression as well as for vascularizing engineered tissues for regenerative medicine. However, bioengineering tissues for transplantation has failed to result in clinical translation due to the lack of proper integrated vasculature for effective oxygen and nutrient delivery. The development of strategies to generate multiscale vascular networks and their direct anastomosis to host vasculature would greatly benefit this formidable goal. In this review, design considerations and technologies for engineering millimeter‐, meso‐, and microscale vessels are discussed. Examples of recent state‐of‐the‐art strategies to engineer multiscale vasculature are also provided. Finally, key challenges limiting the translation of vascularized tissues are identified and perspectives on future directions for exploration are presented.

show abstract

“…Optimized regimes of biophysical stimulation and combinatorial uses of growth factors, small molecules, and metabolic fuel sources will be needed to accelerate engineered muscle maturation in weeks rather than years [1,6]. Biomimetic incorporation of other muscle-resident cells such as fibroblasts, motor neurons [10], and immune [11] and vascular [12,13] cells will allow more accurate modeling of native muscle composition, function, regeneration, and complex disease phenotypes. Incorporating macrophages, in particular, was critical to successful in vitro and in vivo regeneration of adult rat-engineered muscle, highlighting the increased physiological relevance of multicellular models [11].…”

Section: Expert Opinionmentioning

confidence: 99%