Vascularized Biomaterials to Study Cancer Metastasis

Bittner, Katharine R.; Jiménez, Juan M.; Peyton, Shelly R.

doi:10.1002/adhm.201901459

Cited by 23 publications

(12 citation statements)

References 83 publications

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“…Moreover, it is well-known that vasculature structure plays a pivotal role on CTCS extravasation and that the complex interplay between the ECs and cancer cells needs to be reproduced to fully elucidate the mechanisms of cells invasion in a secondary tissue [ 28 , 54 ]. Furthermore, the endothelium is susceptible to different shear stresses by altering morphology, gene expression profiles, ECs-ECM interactions and barrier transport capabilities [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

“…Based on these considerations, further studies could be performed aimed at increasing the level of accuracy of our fluidic platform by associating multiple components typical of the metastatic niche (e.g., chemical signals, cells recreating the tumor stroma, endothelial cells to re recreate the endothelial barrier functions). In addition, biomolecules, as vascular endothelial growth factor (VEGF), can be incorporated in our system, since, for example, VEGF gradients together with shear forces may promote ECs sprouting and vasculogenesis of capillary-sized networks within the ECM [ 28 , 55 ].…”

Section: Discussionmentioning

confidence: 99%

“…After 2 days of culture, HUVECs organized into tubular structures characterized by tight junctions and a physiological vessels permeability [ 27 ]. However, injecting fluid flow resembling the bloodstream and controlling its biophysical properties, crucial for cancer cells migration and invasion, result in being very difficult because syringe or peristaltic pumps cannot be directly connected to the inner vasculature [ 28 ]. On the other hand, although bioprinting techniques allow creating more complex and variable sized networks, they are often hardly accessible due to the high costs.…”

Section: Introductionmentioning

confidence: 99%

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3D Perfusable Hydrogel Recapitulating the Cancer Dynamic Environment to in Vitro Investigate Metastatic Colonization

et al. 2020

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Metastasis is a dynamic process involving the dissemination of circulating tumor cells (CTCs) through blood flow to distant tissues within the body. Nevertheless, the development of an in vitro platform that dissects the crucial steps of metastatic cascade still remains a challenge. We here developed an in vitro model of extravasation composed of (i) a single channel-based 3D cell laden hydrogel representative of the metastatic site, (ii) a circulation system recapitulating the bloodstream where CTCs can flow. Two polymers (i.e., fibrin and alginate) were tested and compared in terms of mechanical and biochemical proprieties. Computational fluid-dynamic (CFD) simulations were also performed to predict the fluid dynamics within the polymeric matrix and, consequently, the optimal culture conditions. Next, once the platform was validated through perfusion tests by fluidically connecting the hydrogels with the external circuit, highly metastatic breast cancer cells (MDA-MB-231) were injected and exposed to physiological wall shear stress (WSS) conditions (5 Dyn/cm2) to assess their migration toward the hydrogel. Results indicated that CTCs arrested and colonized the polymeric matrix, showing that this platform can be an effective fluidic system to model the first steps occurring during the metastatic cascade as well as a potential tool to in vitro elucidate the contribution of hemodynamics on cancer dissemination to a secondary site.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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3D Perfusable Hydrogel Recapitulating the Cancer Dynamic Environment to in Vitro Investigate Metastatic Colonization

et al. 2020

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“…Metastasis is the main critical issue in cancer progression, being responsible for 90% of cancer-related deaths ( 1 ). The way cancer cells manage to detach from the primary tumor, migrate, invade, and follow the metastatic routes ( e.g.…”

Section: Introductionmentioning

confidence: 99%

Molecular and Metabolic Reprogramming: Pulling the Strings Toward Tumor Metastasis

et al. 2021

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Metastasis is a major hurdle to the efficient treatment of cancer, accounting for the great majority of cancer-related deaths. Although several studies have disclosed the detailed mechanisms underlying primary tumor formation, the emergence of metastatic disease remains poorly understood. This multistep process encompasses the dissemination of cancer cells to distant organs, followed by their adaptation to foreign microenvironments and establishment in secondary tumors. During the last decades, it was discovered that these events may be favored by particular metabolic patterns, which are dependent on reprogrammed signaling pathways in cancer cells while they acquire metastatic traits. In this review, we present current knowledge of molecular mechanisms that coordinate the crosstalk between metastatic signaling and cellular metabolism. The recent findings involving the contribution of crucial metabolic pathways involved in the bioenergetics and biosynthesis control in metastatic cells are summarized. Finally, we highlight new promising metabolism-based therapeutic strategies as a putative way of impairing metastasis.

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“…Vascularization is fundamental for engineering artificial organs, as microvessels are required to transport nutrients and oxygen to the cells inside large‐scale tissues [1]. Various strategies have been developed to culture microvessels in vitro [2, 3]. One common method is to seed vascular endothelial cells in a three‐dimensional (3D) hydrogel [2, 4, 5].…”

Section: Introductionmentioning

confidence: 99%

Patterned vascularization in a directional ice‐templated scaffold of decellularized matrix

Song

et al. 2021

Engineering in Life Sciences

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Vascularization is fundamental for large‐scale tissue engineering. Most of the current vascularization strategies including microfluidics and three‐dimensional (3D) printing aim to precisely fabricate microchannels for individual microvessels. However, few studies have examined the remodeling capacity of the microvessels in the engineered constructs, which is important for transplantation in vivo. Here we present a method for patterning microvessels in a directional ice‐templated scaffold of decellularized porcine kidney extracellular matrix. The aligned microchannels made by directional ice templating allowed for fast and efficient cell seeding. The pure decellularized matrix without any fixatives or cross‐linkers maximized the potential of tissue remodeling. Dramatical microvascular remodeling happened in the scaffold in 2 weeks, from small primary microvessel segments to long patterned microvessels. The majority of the microvessels were aligned in parallel and interconnected with each other to form a network. This method is compatible with other engineering techniques, such as microfluidics and 3D printing, and multiple cell types can be co‐cultured to make complex vascularized tissue and organ models.

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Vascularized Biomaterials to Study Cancer Metastasis

Cited by 23 publications

References 83 publications

3D Perfusable Hydrogel Recapitulating the Cancer Dynamic Environment to in Vitro Investigate Metastatic Colonization

3D Perfusable Hydrogel Recapitulating the Cancer Dynamic Environment to in Vitro Investigate Metastatic Colonization

Molecular and Metabolic Reprogramming: Pulling the Strings Toward Tumor Metastasis

Patterned vascularization in a directional ice‐templated scaffold of decellularized matrix

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