Integrated role of human thymic stromal cells in hematopoietic stem cell extravasation

Watson, Sara A.; Javanmardi, Yousef; Zanieri, Luca; Shahreza, Somayeh; Ragazzini, Roberta; Bonfanti, Paola; Moeendarbary, Emad

doi:10.1002/btm2.10454

Cited by 9 publications

(6 citation statements)

References 70 publications

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“…Once primed in µwell culture, µDBOs can be vascularised by seeding with endothelial cells in a matrix that permits vascular formation. Vascular networks form within 4-7 days, which is consistent with systems using similar cells and matrices [44][45][46]. The advantage of this approach is that vasculogenesis can proceed in the presence of the µDBOs, and the two tissues can be subsequently separated and analysed.…”

Section: Discussionsupporting

confidence: 75%

A microphysiological model of bone development and regeneration

et al. 2023

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Endochondral ossification (EO) is an essential biological process than underpins how human bones develop, grow, and heal in the event of a fracture. So much is unknown about this process, thus clinical manifestations of dysregulated EO cannot be adequately treated. This can be partially attributed to the absence of predictive in vitro models of musculoskeletal tissue development and healing, which are integral to the development and preclinical evaluation of novel therapeutics. Microphysiological systems, or organ-on-chip devices, are advanced in vitro models designed for improved biological relevance compared to traditional in vitro culture models. Here we develop a microphysiological model of vascular invasion into developing/regenerating bone, thereby mimicking the process of EO. This is achieved by integrating endothelial cells and organoids mimicking different stages of endochondral bone development within a microfluidic chip. This microphysiological model is able to recreate key events in EO, such as the changing angiogenic profile of a maturing cartilage analogue, and vascular induced expression of the pluripotent transcription factors SOX2 and OCT4 in the cartilage analogue. This system represents an advanced in vitro platform to further EO research, and may also serve as a modular unit to monitor drug responses on such processes as part of a multi-organ system.

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Section: Discussionsupporting

confidence: 75%

A microphysiological model of bone development and regeneration

et al. 2023

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“…Indeed, due to complexities in quantifying / altering the mechanical properties of tissues, the in vivo study of such interactions during TC transmigration is extremely difficult, if not impossible. Building on our refined techniques, we envisage that 3D microvasculature networks [ 69 ] formed within microfluidic platforms [ 70 ] will enable detailed investigation of transmigration mechanics in more physiologically relevant conditions.…”

Section: Summary and Discussionmentioning

confidence: 99%

Endothelium and Subendothelial Matrix Mechanics Modulate Cancer Cell Transendothelial Migration

et al. 2023

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Cancer cell extravasation, a key step in the metastatic cascade, involves cancer cell arrest on the endothelium, transendothelial migration (TEM), followed by the invasion into the subendothelial extracellular matrix (ECM) of distant tissues. While cancer research has mostly focused on the biomechanical interactions between tumor cells (TCs) and ECM, particularly at the primary tumor site, very little is known about the mechanical properties of endothelial cells and the subendothelial ECM and how they contribute to the extravasation process. Here, an integrated experimental and theoretical framework is developed to investigate the mechanical crosstalk between TCs, endothelium and subendothelial ECM during in vitro cancer cell extravasation. It is found that cancer cell actin‐rich protrusions generate complex push–pull forces to initiate and drive TEM, while transmigration success also relies on the forces generated by the endothelium. Consequently, mechanical properties of the subendothelial ECM and endothelial actomyosin contractility that mediate the endothelial forces also impact the endothelium's resistance to cancer cell transmigration. These results indicate that mechanical features of distant tissues, including force interactions between the endothelium and the subendothelial ECM, are key determinants of metastatic organotropism.

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“…Currently, many advanced approaches have been introduced to tissue research that allow for the combination of many of the aforementioned features. Many labs use microfluidic platforms that can mimic, to a great degree, the (patho)physiological functions of tissues and organs [ 166 , 167 , 168 , 169 ]. These chip-like devices consist of microfluidic channels connected to each other, such that cells from different compartments can communicate via their shared fluid.…”

Section: Imaging and Analysis Of Mctsmentioning

confidence: 99%

Applications and Advances of Multicellular Tumor Spheroids: Challenges in Their Development and Analysis

Mitrakas

Tsolou

Didaskalou

et al. 2023

IJMS

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Biomedical research requires both in vitro and in vivo studies in order to explore disease processes or drug interactions. Foundational investigations have been performed at the cellular level using two-dimensional cultures as the gold-standard method since the early 20th century. However, three-dimensional (3D) cultures have emerged as a new tool for tissue modeling over the last few years, bridging the gap between in vitro and animal model studies. Cancer has been a worldwide challenge for the biomedical community due to its high morbidity and mortality rates. Various methods have been developed to produce multicellular tumor spheroids (MCTSs), including scaffold-free and scaffold-based structures, which usually depend on the demands of the cells used and the related biological question. MCTSs are increasingly utilized in studies involving cancer cell metabolism and cell cycle defects. These studies produce massive amounts of data, which demand elaborate and complex tools for thorough analysis. In this review, we discuss the advantages and disadvantages of several up-to-date methods used to construct MCTSs. In addition, we also present advanced methods for analyzing MCTS features. As MCTSs more closely mimic the in vivo tumor environment, compared to 2D monolayers, they can evolve to be an appealing model for in vitro tumor biology studies.

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Integrated role of human thymic stromal cells in hematopoietic stem cell extravasation

Cited by 9 publications

References 70 publications

A microphysiological model of bone development and regeneration

A microphysiological model of bone development and regeneration

Endothelium and Subendothelial Matrix Mechanics Modulate Cancer Cell Transendothelial Migration

Applications and Advances of Multicellular Tumor Spheroids: Challenges in Their Development and Analysis

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