Hydrogels to model 3D in vitro microenvironment of tumor vascularization

Song, Hyun‐Ho Greco; Park, Kyung Min; Gerecht, Sharon

doi:10.1016/j.addr.2014.06.002

Cited by 139 publications

(118 citation statements)

References 140 publications

(174 reference statements)

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“…Conventional two-dimensional (2D) monolayer models of human cancers have been important tools for studying cancer biology and developing anticancer therapeutics, and provide a valuable addition to what can be learned using animal models. However, it is becoming increasingly clear that conventional 2D culture models are insufficient to recapitulate many important characteristics of tumors in vivo and are often poorly predictive of drug response in humans 29–31 . In contrast to 2D monolayer culture models, tumor cells in vivo are supported by a 3D extracellular matrix (ECM) and non-tumor cells, including endothelial cells, immune cells, and other stromal cells 1,32 .…”

Section: Biomaterials To Create 3d Tumor Modelsmentioning

confidence: 99%

Biomaterials and emerging anticancer therapeutics: engineering the microenvironment

2015

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The microenvironment is increasingly recognized to play key roles in cancer, and biomaterials provide a means to engineer microenvironments both in vitro and in vivo to study and manipulate cancer. In vitro cancer models using 3D matrices recapitulate key elements of the tumor microenvironment and have revealed new aspects of cancer biology. Cancer vaccines based on some of the same biomaterials have, in parallel, allowed for the engineering of durable prophylactic and therapeutic anticancer activity in preclinical studies, and some of these vaccines have moved to clinical trials. The impact of biomaterials engineering on cancer treatment is expected to further increase in importance in the years to come.

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Section: Biomaterials To Create 3d Tumor Modelsmentioning

confidence: 99%

Biomaterials and emerging anticancer therapeutics: engineering the microenvironment

2015

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“…Transwell ®), as well as immunofluorescent or immunohistochemical staining and imaging [4,19,20]. However, the inability of 2D culture to accurately predict therapeutic response and the complexity of animal models has paved the way for the development of 3D in vitro models, which utilize materials such as hydrogels to recapitulate elements of the tumor microenvironment [21][22][23]. To date, 3D in vitro models for GBM primarily incorporate only tumor cells, despite the demonstrated contributions of additional cell types to in vivo GBM behavior [6,[24][25][26][27][28][29][30].…”

Section: Introductionmentioning

confidence: 99%

Perivascular signals alter global gene expression profile of glioblastoma and response to temozolomide in a gelatin hydrogel

Harley

Ngo

2018

Preprint

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Glioblastoma (GBM) is the most common primary malignant brain tumor, with patients exhibiting poor survival (median survival time: 15 months). Difficulties in treating GBM include not only the inability to resect the diffusively-invading tumor cells but also therapeutic resistance. The perivascular niche within the GBM tumor microenvironment contributes significantly to tumor cell invasion, cancer stem cell maintenance, and has been shown to protect tumor cells from radiation and chemotherapy. In this study, we describe the development of an in vitro artificial perivascular niche (PVN), culturing endothelial and stromal cells along with GBM cells within a methacrylamide-functionalized gelatin hydrogel, in order to examine howthe presence of the PVN alters global genomic expression profiles. Using RNA-seq, we demonstrate that the inclusion of perivascular niche cells with GBM cells upregulates genes related to angiogenesis and remodeling, while downregulated genes are related to cell cycle and DNA damage repair.Signaling pathways and genes commonly implicated in GBM malignancy, such as MGMT, EGFR, PI3K-Akt signaling, and Ras/MAPK signaling are also upregulated in the presence of perivascular niche cells. We describe the kinetics of gene expression within the PVN hydrogels over a course of 14 days, observing the patterns associated with previously-observed GBMmediated endothelial network co-option and regression that are altered in the presence of covalently-bound hyaluronic acid. We finally examine the effect of PVN culture on GBM cell responsiveness to temozolomide, a frontline chemotherapy used clinically against GBM.Notably, the presence of a PVN leads to significantly increased TMZ resistance compared to hydrogels containing only GBM cells. Overall, these results demonstrate that inclusion of cellular and matrix-associated elements of the PVN within in vitro models of GBM provide critical signals to regulate the phenotype and therapeutic responsiveness of GBM cells.

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“…One particular approach to create in vitro models of blood vessels is worth mentioning for microbubble-related medical applications, since it consists of embedding a functional vascular network in a hydrogel ECM-like matrix, which can act as the surrounding tissue. 63 This approach would allow not only the study of the microbubble delivery under physiological flow conditions followed by the rupture of the barrier upon bubble excitation, but also the visualization of the actual release of drugs and the assessment of its penetration into the tissue. Moya et al 64 reported the spontaneous formation of such a complex vasculature in a fibrin matrix.…”

Section: More Complex Cellular Models: Toward Mimicking the In Vivmentioning

confidence: 99%

In vitro methods to study bubble-cell interactions: Fundamentals and therapeutic applications

et al. 2016

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Besides their use as contrast agents for ultrasound imaging, microbubbles are increasingly studied for a wide range of therapeutic applications. In particular, their ability to enhance the uptake of drugs through the permeabilization of tissues and cell membranes shows great promise. In order to fully understand the numerous paths by which bubbles can interact with cells and the even larger number of possible biological responses from the cells, thorough and extensive work is necessary. In this review, we consider the range of experimental techniques implemented in in vitro studies with the aim of elucidating these microbubble-cell interactions. First of all, the variety of cell types and cell models available are discussed, emphasizing the need for more and more complex models replicating in vivo conditions together with experimental challenges associated with this increased complexity. Second, the different types of stabilized microbubbles and more recently developed droplets and particles are presented, followed by their acoustic or optical excitation methods. Finally, the techniques exploited to study the microbubble-cell interactions are reviewed. These techniques operate over a wide range of timescales, or even off-line, revealing particular aspects or subsequent effects of these interactions. Therefore, knowledge obtained from several techniques must be combined to elucidate the underlying processes. V C 2016 AIP Publishing LLC.

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Hydrogels to model 3D in vitro microenvironment of tumor vascularization

Cited by 139 publications

References 140 publications

Biomaterials and emerging anticancer therapeutics: engineering the microenvironment

Biomaterials and emerging anticancer therapeutics: engineering the microenvironment

Perivascular signals alter global gene expression profile of glioblastoma and response to temozolomide in a gelatin hydrogel

In vitro methods to study bubble-cell interactions: Fundamentals and therapeutic applications

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