Genipin-crosslinked double PLL membranes overcome the strength-diffusion trade-off in cell encapsulation without compromising biocompatibility

Edorta Santos-Vizcaino, María Virumbrales-Muñoz, Ainhoa Gonzalez-Pujana, Gary D Luker, Ignacio Ochoa, Rosa Maria Hernandez, Jose Luis Pedraz

Cell microencapsulation technologies allow non-autologous implantation of therapeutic cells for sustained drug delivery purposes. The perm-selective membrane of these systems provides resistance to rupture, stablishes the upper molecular weight limit in bidirectional diffusion of molecules, and affects biocompatibility. Thus, despite being a decisive factor to succeed in terms of biosafety and therapeutic efficacy, little progress has been made in its optimization so far. Here we show that,...

Published: 01/12/2025

International journal of pharmaceutics pmid:39799997

Immune cells and inflammatory mediators cause endothelial dysfunction in a vascular microphysiological system

Aishwarya Rengarajan, Hannah E Goldblatt, David J Beebe, María Virumbrales-Muñoz, Derek S Boeldt

Functional assessment of endothelium serves as an important indicator of vascular health and is compromised in vascular disorders including hypertension, atherosclerosis, and preeclampsia. Endothelial dysfunction in these cases is linked to dysregulation of the immune system involving both changes to immune cells and increased secretion of inflammatory cytokines. Herein, we utilize a well-established microfluidic device to generate a 3-dimensional vascular microphysiological system (MPS)...

Published: 02/16/2024

Lab on a chip pmid:38363157

Microphysiological systems for solid tumor immunotherapy: opportunities and challenges

Sara Abizanda-Campo, María Virumbrales-Muñoz, Mouhita Humayun, Ines Marmol, David J Beebe, Ignacio Ochoa, Sara Oliván, Jose M Ayuso

Immunotherapy remains more effective for hematologic tumors than for solid tumors. One of the main challenges to immunotherapy of solid tumors is the immunosuppressive microenvironment these tumors generate, which limits the cytotoxic capabilities of immune effector cells (e.g., cytotoxic T and natural killer cells). This microenvironment is characterized by hypoxia, nutrient starvation, accumulated waste products, and acidic pH. Tumor-hijacked cells, such as fibroblasts, macrophages, and T...

Published: 12/18/2023

Microsystems & nanoengineering pmid:38106674

Author Correction: Microphysiological model reveals the promise of memory-like natural killer cell immunotherapy for HIV^± cancer

Jose M Ayuso, Mehtab Farooqui, María Virumbrales-Muñoz, Katheryn Denecke, Shujah Rehman, Rebecca Schmitz, Jorge F Guerrero, Cristina Sanchez-de-Diego, Sara Abizanda Campo, Elizabeth M Maly, Matthew H Forsberg, Sheena C Kerr, Robert Striker, Nathan M Sherer, Paul M Harari, Christian M Capitini, Melissa C Skala, David J Beebe

No abstract

Published: 11/10/2023

Nature communications pmid:37949872

Microphysiological model reveals the promise of memory-like natural killer cell immunotherapy for HIV^± cancer

Jose M Ayuso, Mehtab Farooqui, María Virumbrales-Muñoz, Katheryn Denecke, Shujah Rehman, Rebecca Schmitz, Jorge F Guerrero, Cristina Sanchez-de-Diego, Sara Abizanda Campo, Elizabeth M Maly, Matthew H Forsberg, Sheena C Kerr, Robert Striker, Nathan M Sherer, Paul M Harari, Christian M Capitini, Melissa C Skala, David J Beebe

Numerous studies are exploring the use of cell adoptive therapies to treat hematological malignancies as well as solid tumors. However, there are numerous factors that dampen the immune response, including viruses like human immunodeficiency virus. In this study, we leverage human-derived microphysiological models to reverse-engineer the HIV-immune system interaction and evaluate the potential of memory-like natural killer cells for HIV^(+) head and neck cancer, one of the most common tumors in...

Published: 10/21/2023

Nature communications pmid:37865647

Griddient: a microfluidic array to generate reconfigurable gradients on-demand for spatial biology applications

Cristina Sanchez-de-Diego, María Virumbrales-Muñoz, Brock Hermes, Terry D Juang, Duane S Juang, Jeremiah Riendeau, Emmanuel Contreras Guzman, Catherine A Reed-McBain, Sara Abizanda-Campo, Janmesh Patel, Nicholas J Hess, Melissa C Skala, David J Beebe, Jose M Ayuso

Biological tissues are highly organized structures where spatial-temporal gradients (e.g., nutrients, hypoxia, cytokines) modulate multiple physiological and pathological processes including inflammation, tissue regeneration, embryogenesis, and cancer progression. Current in vitro technologies struggle to capture the complexity of these transient microenvironmental gradients, do not provide dynamic control over the gradient profile, are complex and poorly suited for high throughput applications....

Published: 09/09/2023

Communications biology pmid:37689746

Microfluidics in vascular biology research: a critical review for engineers, biologists, and clinicians

Grigor Simitian, María Virumbrales-Muñoz, Cristina Sánchez-de-Diego, David J Beebe, David Kosoff

Neovascularization, the formation of new blood vessels, has received much research attention due to its implications for physiological processes and diseases. Most studies using traditional in vitro and in vivo platforms find challenges in recapitulating key cellular and mechanical cues of the neovascularization processes. Microfluidic in vitro models have been presented as an alternative to these limitations due to their capacity to leverage microscale physics to control cell organization and...

Published: 09/01/2022

Lab on a chip pmid:36047330

Microfluidic Model to Evaluate Astrocyte Activation in Penumbral Region following Ischemic Stroke

Kathryn M Denecke, Catherine A McBain, Brock G Hermes, Sireesh Kumar Teertam, Mehtab Farooqui, María Virumbrales-Muñoz, Jennifer Panackal, David J Beebe, Bolanle Famakin, Jose M Ayuso

Stroke is one of the main causes of death in the US and post-stroke treatment options remain limited. Ischemic stroke is caused by a blood clot that compromises blood supply to the brain, rapidly leading to tissue death at the core of the infarcted area surrounded by a hypoxic and nutrient-starved region known as the penumbra. Recent evidence suggests that astrocytes in the penumbral region play a dual role in stroke response, promoting further neural and tissue damage or improving tissue repair...

Published: 08/12/2022

Cells pmid:35954200

A Label-Free Segmentation Approach for Intravital Imaging of Mammary Tumor Microenvironment

Brian M Burkel, David R Inman, María Virumbrales-Muñoz, Erica J Hoffmann, Suzanne M Ponik

The ability to visualize complex and dynamic physiological interactions between numerous cell types and the extracellular matrix (ECM) within a live tumor microenvironment is an important step toward understanding mechanisms that regulate tumor progression. While this can be accomplished through current intravital imaging techniques, it remains challenging due to the heterogeneous nature of tissues and the need for spatial context within the experimental observation. To this end, we have...

Published: 06/13/2022

Journal of visualized experiments : JoVE pmid:35695521

A role for microfluidic systems in precision medicine

Jose M Ayuso, María Virumbrales-Muñoz, Joshua M Lang, David J Beebe

Precision oncology continues to challenge the "one-size-fits-all" dogma. Under the precision oncology banner, cancer patients are screened for molecular tumor alterations that predict treatment response, ideally leading to optimal treatments. Functional assays that directly evaluate treatment efficacy on the patient's cells offer an alternative and complementary tool to improve the accuracy of precision oncology. Unfortunately, traditional Petri dish-based assays overlook much tumor complexity,...

Published: 06/02/2022

Nature communications pmid:35654785

Models of Renal Cell Carcinoma Used to Investigate Molecular Mechanisms and Develop New Therapeutics

Daniel D Shapiro, Maria Virumbrales-Muñoz, David J Beebe, E Jason Abel

Modeling renal cell carcinoma is critical to investigating tumor biology and therapeutic mechanisms. Multiple systems have been developed to represent critical components of the tumor and its surrounding microenvironment. Prominent in vitro models include traditional cell cultures, 3D organoid models, and microphysiological devices. In vivo models consist of murine patient derived xenografts or genetically engineered mice. Each system has unique advantages as well as limitations and researchers...

Published: 04/25/2022

Frontiers in oncology pmid:35463327

Microphysiological model of renal cell carcinoma to inform anti-angiogenic therapy

María Virumbrales-Muñoz, Jose M Ayuso, Jack R Loken, Kathryn M Denecke, Shujah Rehman, Melissa C Skala, E Jason Abel, David J Beebe

Renal cell carcinomas are common genitourinary tumors characterized by high vascularization and strong reliance on glycolysis. Despite the many available therapies for renal cell carcinomas, first-line targeted therapies, such as cabozantinib, and durable reaponses are seen in only a small percentage of patients. Yet, little is known about the mechanisms that drive response (or lack thereof). This dearth of knowledge can be explained by the dynamic and complex microenvironment of renal...

Published: 03/17/2022

Biomaterials pmid:35299086

Primary head and neck tumour-derived fibroblasts promote lymphangiogenesis in a lymphatic organotypic co-culture model

Karina M Lugo-Cintrón, José M Ayuso, Mouhita Humayun, Max M Gong, Sheena C Kerr, Suzanne M Ponik, Paul M Harari, María Virumbrales-Muñoz, David J Beebe

BACKGROUND: In head and neck cancer, intratumour lymphatic density and tumour lymphangiogenesis have been correlated with lymphatic metastasis, making lymphangiogenesis a promising therapeutic target. However, inter-patient tumour heterogeneity makes it challenging to predict tumour progression and lymph node metastasis. Understanding the lymphangiogenic-promoting factors leading to metastasis (e.g., tumour-derived fibroblasts or TDF), would help develop strategies to improve patient outcomes.

Published: 10/21/2021

EBioMedicine pmid:34673450

Microfluidic tumor-on-a-chip model to evaluate the role of tumor environmental stress on NK cell exhaustion

Jose M Ayuso, Shujah Rehman, Maria Virumbrales-Munoz, Patrick H McMinn, Peter Geiger, Cate Fitzgerald, Tiffany Heaster, Melissa C Skala, David J Beebe

Solid tumors generate a suppressive environment that imposes an overwhelming burden on the immune system. Nutrient depletion, waste product accumulation, hypoxia, and pH acidification severely compromise the capacity of effector immune cells such as T and natural killer (NK) cells to destroy cancer cells. However, the specific molecular mechanisms driving immune suppression, as well as the capacity of immune cells to adapt to the suppressive environment, are not completely understood. Thus,...

Published: 02/18/2021

Science advances pmid:33597234

Elucidating cancer-vascular paracrine signaling using a human organotypic breast cancer cell extravasation model

Mouhita Humayun, Jose M Ayuso, Raven A Brenneke, María Virumbrales-Muñoz, Karina Lugo-Cintrón, Sheena Kerr, Suzanne M Ponik, David J Beebe

In cancer metastasis, extravasation refers to the process where tumor cells exit the bloodstream by crossing the endothelium and invade the surrounding tissue. Tumor cells engage in complex crosstalk with other active players such as the endothelium leading to changes in functional behavior that exert pro-extravasation effects. Most in vitro studies to date have only focused on the independent effects of molecular targets on the functional changes of cancer cell extravasation behavior. However,...

Published: 02/16/2021

Biomaterials pmid:33592387

Toward improved <em>in vitro</em> models of human cancer

Jose M Ayuso, Keon-Young Park, María Virumbrales-Muñoz, David J Beebe

Cancer is a leading cause of death across the world and continues to increase in incidence. Despite years of research, multiple tumors (e.g., glioblastoma, pancreatic cancer) still have limited treatment options in the clinic. Additionally, the attrition rate and cost of drug development have continued to increase. This trend is partly explained by the poor predictive power of traditional in vitro tools and animal models. Moreover, multiple studies have highlighted that cell culture in...

Published: 02/03/2021

APL bioengineering pmid:33532672

Force Spectroscopy Imaging and Constriction Assays Reveal the Effects of Graphene Oxide on the Mechanical Properties of Alginate Microcapsules

María Virumbrales-Muñoz, Laura Paz-Artigas, Jesús Ciriza, Clara Alcaine, Albert Espona-Noguera, Manuel Doblaré, Laura Sáenz Del Burgo, Kaoutar Ziani, Jose Luis Pedraz, Luis Fernández, Ignacio Ochoa

Microencapsulation of cells in hydrogel-based porous matrices is an approach that has demonstrated great success in regenerative cell therapy. These microcapsules work by concealing the exogenous cells and materials in a robust biomaterial that prevents their recognition by the immune system. A vast number of formulations and additives are continuously being tested to optimize cell viability and mechanical properties of the hydrogel. Determining the effects of new microcapsule additives is a...

Published: 12/18/2020

ACS biomaterials science & engineering pmid:33337130

Microfluidic Tumor-on-a-Chip Model to Study Tumor Metabolic Vulnerability

Jose M Ayuso, Shujah Rehman, Mehtab Farooqui, María Virumbrales-Muñoz, Vijayasaradhi Setaluri, Melissa C Skala, David J Beebe

Tumor-specific metabolic adaptations offer an interesting therapeutic opportunity to selectively destroy cancer cells. However, solid tumors also present gradients of nutrients and waste products across the tumor mass, forcing tumor cells to adapt their metabolism depending on nutrient availability in the surrounding microenvironment. Thus, solid tumors display a heterogenous metabolic phenotype across the tumor mass, which complicates the design of effective therapies that target all the tumor...

Published: 12/02/2020

International journal of molecular sciences pmid:33260673

Organotypic primary blood vessel models of clear cell renal cell carcinoma for single-patient clinical trials

María Virumbrales-Muñoz, Jiong Chen, Jose Ayuso, Moonhee Lee, E Jason Abel, David J Beebe

Clear cell renal cell carcinoma (ccRCC) is a common genitourinary cancer associated with the development of abnormal tumor angiogenesis. Although multiple anti-angiogenic therapies have been developed, responses to individual treatment are highly variable between patients. Thus, the use of one-patient clinical trials has been suggested as an alternative to standard trials. We used a microfluidic device to generate organotypic primary patient-specific blood vessel models using normal (NEnC) and...

Published: 10/26/2020

Lab on a chip pmid:33103699

Microfluidic lumen-based systems for advancing tubular organ modeling

María Virumbrales-Muñoz, José M Ayuso, Max M Gong, Mouhita Humayun, Megan K Livingston, Karina M Lugo-Cintrón, Patrick McMinn, Yasmín R Álvarez-García, David J Beebe

Microfluidic lumen-based systems are microscale models that recapitulate the anatomy and physiology of tubular organs. These technologies can mimic human pathophysiology and predict drug response, having profound implications for drug discovery and development. Herein, we review progress in the development of microfluidic lumen-based models from the 2000s to the present. The core of the review discusses models for mimicking blood vessels, the respiratory tract, the gastrointestinal tract, renal...

Published: 08/08/2020

Chemical Society reviews pmid:32760967

Breast Fibroblasts and ECM Components Modulate Breast Cancer Cell Migration Through the Secretion of MMPs in a 3D Microfluidic Co-Culture Model

Karina M Lugo-Cintrón, Max M Gong, José M Ayuso, Lucas A Tomko, David J Beebe, María Virumbrales-Muñoz, Suzanne M Ponik

The extracellular matrix (ECM) composition greatly influences cancer progression, leading to differential invasion, migration, and metastatic potential. In breast cancer, ECM components, such as fibroblasts and ECM proteins, have the potential to alter cancer cell migration. However, the lack of in vitro migration models that can vary ECM composition limits our knowledge of how specific ECM components contribute to cancer progression. Here, a microfluidic model was used to study the effect of 3D...

Published: 05/10/2020

Cancers pmid:32384738

Matrix density drives 3D organotypic lymphatic vessel activation in a microfluidic model of the breast tumor microenvironment

Karina M Lugo-Cintrón, José M Ayuso, Bridget R White, Paul M Harari, Suzanne M Ponik, David J Beebe, Max M Gong, María Virumbrales-Muñoz

Lymphatic vessels (LVs) have been suggested as a preferential conduit for metastatic progression in breast cancer, where a correlation between the occurrence of lymph node metastasis and an increased extracellular matrix (ECM) density has been reported. However, the effect of ECM density on LV function is largely unknown. To better understand these effects, we used a microfluidic device to recreate tubular LVs in a collagen type I matrix. The density of the matrix was tailored to mimic normal...

Published: 04/17/2020

Lab on a chip pmid:32297896

Evaluation of PEG-based hydrogel influence on estrogen receptor driven responses in MCF7 breast cancer cells

Megan K Livingston, Molly M Morgan, William T Daly, William L Murphy, Brian P Johnson, David J Beebe, Maria Virumbrales-Muñoz

Extracellular matrix (ECM) mimicking hydrogel scaffolds have greatly improved the physiological relevance of in vitro assays, but introduce another dimension that creates variability in cell related readouts when compared to traditional 2D cells-on-plastic assays. We have developed a synthetic poly(ethylene glycol) (PEG) based ECM mimicking hydrogel and tested it against two gold standard animal-based naturally derived hydrogel scaffolds in MCF7 cell response. We have used the percent...

Published: 01/17/2020

ACS biomaterials science & engineering pmid:31942444

Author Correction: Enabling cell recovery from 3D cell culture microfluidic devices for tumour microenvironment biomarker profiling

María Virumbrales-Muñoz, Jose M Ayuso, Alodia Lacueva, Teodora Randelovic, Megan K Livingston, David J Beebe, Sara Oliván, Desirée Pereboom, Manuel Doblare, Luis Fernández, Ignacio Ochoa

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Published: 01/16/2020

Scientific reports pmid:31937889

Force spectroscopy-based simultaneous topographical and mechanical characterization to study polymer-to-polymer interactions in coated alginate microspheres

Maria Virumbrales-Muñoz, Edorta Santos-Vizcaino, Laura Paz, Amparo Maria Gallardo-Moreno, Gorka Orive, Rosa Maria Hernandez, Manuel Doblaré, Maria Luisa Gonzalez-Martin, Luis Jose Fernández, Jose Luis Pedraz, Ignacio Ochoa

Cell-laden hydrogel microspheres have shown encouraging outcomes in the fields of drug delivery, tissue engineering or regenerative medicine. Beyond the classical single coating with polycations, many other different coating designs have been reported with the aim of improving mechanical properties and in vivo performance of the microspheres. Among the most common strategies are the inclusion of additional polycation coatings and the covalent bonding of the semi-permeable membranes with...

Published: 12/29/2019

Scientific reports pmid:31882828

Development of a Microfluidic Array to Study Drug Response in Breast Cancer

María Virumbrales-Muñoz, Megan K Livingston, Mehtab Farooqui, Melissa C Skala, David J Beebe, Jose M Ayuso

Luminal geometries are common structures in biology, which are challenging to mimic using conventional in vitro techniques based on the use of Petri dishes. In this context, microfluidic systems can mimic the lumen geometry, enabling a large variety of studies. However, most microfluidic models still rely on polydimethylsiloxane (PDMS), a material that is not amenable for high-throughput fabrication and presents some limitations compared with other materials such as polystyrene. Thus, we have...

Published: 12/06/2019

Molecules (Basel, Switzerland) pmid:31801265

Tumor-on-a-chip: a microfluidic model to study cell response to environmental gradients

Jose M Ayuso, Maria Virumbrales-Munoz, Patrick H McMinn, Shujah Rehman, Ismael Gomez, Mohammad R Karim, Regan Trusttchel, Kari B Wisinski, David J Beebe, Melissa C Skala

Limited blood supply and rapid tumor metabolism within solid tumors leads to nutrient starvation, waste product accumulation and the generation of pH gradients across the tumor mass. These environmental conditions modify multiple cellular functions, including metabolism, proliferation, and drug response. However, capturing the spatial metabolic and phenotypic heterogeneity of the tumor with classic in vitro models remains challenging. Thus, in this work a microfluidic tumor slice model was...

Published: 09/12/2019

Lab on a chip pmid:31506657

Enabling cell recovery from 3D cell culture microfluidic devices for tumour microenvironment biomarker profiling

María Virumbrales-Muñoz, Jose M Ayuso, Alodia Lacueva, Teodora Randelovic, Megan K Livingston, David J Beebe, Sara Oliván, Desirée Pereboom, Manuel Doblare, Luis Fernández, Ignacio Ochoa

The tumour microenvironment (TME) has recently drawn much attention due to its profound impact on tumour development, drug resistance and patient outcome. There is an increasing interest in new therapies that target the TME. Nonetheless, most established in vitro models fail to include essential cues of the TME. Microfluidics can be used to reproduce the TME in vitro and hence provide valuable insight on tumour evolution and drug sensitivity. However, microfluidics remains far from...

Published: 04/19/2019

Scientific reports pmid:30996291

Modulation of Antioxidant Potential with Coenzyme Q10 Suppressed Invasion of Temozolomide-Resistant Rat Glioma <em>In Vitro</em> and <em>In Vivo</em>

Sonja Stojković Burić, Ana Podolski-Renić, Jelena Dinić, Tijana Stanković, Mirna Jovanović, Stefan Hadžić, Jose M Ayuso, María Virumbrales-Muñoz, Luis J Fernández, Ignacio Ochoa, Victor M Pérez-García, Milica Pešić

The main reasons for the inefficiency of standard glioblastoma (GBM) therapy are the occurrence of chemoresistance and the invasion of GBM cells into surrounding brain tissues. New therapeutic approaches obstructing these processes may provide substantial survival improvements. The purpose of this study was to assess the potential of lipophilic antioxidant coenzyme Q10 (CoQ10) as a scavenger of reactive oxygen species (ROS) to increase sensitivity to temozolomide (TMZ) and suppress glioma cell...

Published: 04/16/2019

Oxidative medicine and cellular longevity pmid:30984333

Patient-specific organotypic blood vessels as an in vitro model for anti-angiogenic drug response testing in renal cell carcinoma

José A Jiménez-Torres, María Virumbrales-Muñoz, Kyung E Sung, Moon Hee Lee, E Jason Abel, David J Beebe

BACKGROUND: Anti-angiogenic treatment failure is often attributed to drug resistance, unsuccessful drug delivery, and tumor heterogeneity. Recent studies have speculated that anti-angiogenic treatments may fail due to characteristics inherent to tumor-associated blood vessels. Tumor-associated blood vessels are phenotypically different from their normal counterparts, having defective or permeable endothelial monolayers, abnormal sprouts, and abnormal vessel hierarchy. Therefore, to predict the...

Published: 03/24/2019

EBioMedicine pmid:30902740

Evaluating natural killer cell cytotoxicity against solid tumors using a microfluidic model

Jose M Ayuso, Regan Truttschel, Max M Gong, Mouhita Humayun, Maria Virumbrales-Munoz, Ross Vitek, Mildred Felder, Stephen D Gillies, Paul Sondel, Kari B Wisinski, Manish Patankar, David J Beebe, Melissa C Skala

Immunotherapies against solid tumors face additional challenges compared with hematological cancers. In solid tumors, immune cells and antibodies need to extravasate from vasculature, find the tumor, and migrate through a dense mass of cells. These multiple steps pose significant obstacles for solid tumor immunotherapy and their study has remained difficult using classic in vitro models based on Petri dishes. In this work, a microfluidic model has been developed to study natural killer cell...

Published: 02/07/2019

Oncoimmunology pmid:30723584

Multiwell capillarity-based microfluidic device for the study of 3D tumour tissue-2D endothelium interactions and drug screening in co-culture models

María Virumbrales-Muñoz, José María Ayuso, Marta Olave, Rosa Monge, Diego de Miguel, Luis Martínez-Lostao, Séverine Le Gac, Manuel Doblare, Ignacio Ochoa, Luis J Fernandez

The tumour microenvironment is very complex, and essential in tumour development and drug resistance. The endothelium is critical in the tumour microenvironment: it provides nutrients and oxygen to the tumour and is essential for systemic drug delivery. Therefore, we report a simple, user-friendly microfluidic device for co-culture of a 3D breast tumour model and a 2D endothelium model for cross-talk and drug delivery studies. First, we demonstrated the endothelium was functional, whereas the...

Published: 09/22/2017

Scientific reports pmid:28931839

Alkynyl gold(I) complex triggers necroptosis via ROS generation in colorectal carcinoma cells

Inés Mármol, María Virumbrales-Muñoz, Javier Quero, Cristina Sánchez-de-Diego, Luis Fernández, Ignacio Ochoa, Elena Cerrada, Mª Jesús Rodríguez Yoldi

Given the rise of apoptosis-resistant tumors, there exist a growing interest in developing new drugs capable of inducing different types of cell death to reduce colorectal cancer-related death rates. As apoptosis and necroptosis do not share cellular machinery, necroptosis induction may have a great therapeutic potential on those apoptosis-resistant cancers, despite the inflammatory effects associated with it. We have synthesized an alkynyl gold(I) complex [Au(CC-2-NC(5)H(4))(PTA)] whose...

Published: 09/12/2017

Journal of inorganic biochemistry pmid:28892675

Glioblastoma on a microfluidic chip: Generating pseudopalisades and enhancing aggressiveness through blood vessel obstruction events

Jose M Ayuso, Rosa Monge, Alicia Martínez-González, María Virumbrales-Muñoz, Guillermo A Llamazares, Javier Berganzo, Aurelio Hernández-Laín, Jorge Santolaria, Manuel Doblaré, Christopher Hubert, Jeremy N Rich, Pilar Sánchez-Gómez, Víctor M Pérez-García, Ignacio Ochoa, Luis J Fernández

CONCLUSIONS: This paper shows the potential of microfluidic devices as advanced artificial systems capable of modeling in vivo nutrient and oxygen gradients during tumor evolution.

Published: 01/08/2017

Neuro-oncology pmid:28062831

Development and characterization of a microfluidic model of the tumour microenvironment

Jose M Ayuso, María Virumbrales-Muñoz, Alodia Lacueva, Pilar M Lanuza, Elisa Checa-Chavarria, Pablo Botella, Eduardo Fernández, Manuel Doblare, Simon J Allison, Roger M Phillips, Julián Pardo, Luis J Fernandez, Ignacio Ochoa

The physical microenvironment of tumours is characterized by heterotypic cell interactions and physiological gradients of nutrients, waste products and oxygen. This tumour microenvironment has a major impact on the biology of cancer cells and their response to chemotherapeutic agents. Despite this, most in vitro cancer research still relies primarily on cells grown in 2D and in isolation in nutrient- and oxygen-rich conditions. Here, a microfluidic device is presented that is easy to use and...

Published: 11/01/2016

Scientific reports pmid:27796335

Graphene oxide increases the viability of C2C12 myoblasts microencapsulated in alginate

J Ciriza, L Saenz del Burgo, M Virumbrales-Muñoz, I Ochoa, L J Fernandez, G Orive, R M Hernandez, J L Pedraz

Cell microencapsulation represents a great promise for long-term drug delivery, but still several challenges need to be overcome before its translation into the clinic, such as the long term cell survival inside the capsules. On this regard, graphene oxide has shown to promote proliferation of different cell types either in two or three dimensions. Therefore, we planned to combine graphene oxide with the cell microencapsulation technology. We first studied the effect of this material on the...

Published: 07/30/2015

International journal of pharmaceutics pmid:26220651