Microheart: A microfluidic pump for functional vascular culture in microphysiological systems

Offeddu, Giovanni S.; Serrano, Jean Carlos; Chen, Sophia W.; Shelton, Sarah E.; Shin, Yoojin; Floryan, Marie; Kamm, Roger D.

doi:10.1016/j.jbiomech.2021.110330

Cited by 25 publications

(30 citation statements)

References 30 publications

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“…The morphology, cellular organization, and barrier function of the BBB are recapitulated in our model, which features the smallest diameters of perfusable BBB vessels reported to date ( 21 , 71 ). Some limitations of our model include the lack of relevant fluid flows, which can be addressed with the use of a pressure controller, as previously done ( 72 , 73 ), and the lack of immune cells or neurons of the brain, which are involved in transport and clearance of solutes at the BBB ( 74 ). These will be a focus of future work.…”

Section: Discussionmentioning

confidence: 99%

A predictive microfluidic model of human glioblastoma to assess trafficking of blood–brain barrier-penetrant nanoparticles

Straehla

Hajal

Safford

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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Significance The blood–brain barrier represents a major therapeutic challenge for the treatment of glioblastoma, and there is an unmet need for in vitro models that recapitulate human biology and are predictive of in vivo response. Here, we present a microfluidic model of vascularized glioblastoma featuring a tumor spheroid in direct contact with self-assembled vascular networks comprising human endothelial cells, astrocytes, and pericytes. This model was designed to accelerate the development of targeted nanotherapeutics and enabled rigorous assessment of a panel of surface-functionalized nanoparticles designed to exploit a receptor overexpressed in tumor-associated vasculature. Trafficking and efficacy data in the in vitro model compared favorably to parallel in vivo data, highlighting the utility of the vascularized glioblastoma model for therapeutic development.

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Section: Discussionmentioning

confidence: 99%

A predictive microfluidic model of human glioblastoma to assess trafficking of blood–brain barrier-penetrant nanoparticles

Straehla

Hajal

Safford

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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“…MVNs were formed here with primary human umbilical vein ECs (HUVECs) and lung FBs, which were chosen for their vasculogenic potential and robust formation of perfusable MVNs even when exposed to pro-inflammatory factors 23,47 . Future modifications of the models may include immortalized MVN cells sources with improved reproducibility 60 , or primary mammary ECs and FBs cultured under constant vascular flow 61 for improved physiological tissue fidelity and model longevity. Patient-derived tumoroids including native immune cell populations and ECM 13 may also be incorporated in the models to assess the efficacy of immunotherapies.…”

Section: Discussionmentioning

confidence: 99%

Personalized models of breast cancer desmoplasia reveal biomechanical determinants of drug penetration

Offeddu

Haase

Wan

et al. 2021

Preprint

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Breast cancer desmoplasia heterogeneity contributes to high disease mortality due to discrepancies in treatment efficacy between patients. Personalized in vitro breast cancer models can be used for high throughput testing and ranking of therapeutic strategies to normalize the aberrant microenvironment in a patient-specific manner. Here, tumoroids assembled from patient-derived cells cultured in microphysiological systems including perfusable microvasculature reproduce key aspects of stromal and vascular dysfunction. Increased hyaluronic acid and collagen deposition, loss of vascular glycocalyx and reduced perfusion, and elevated interstitial fluid pressure in the models result in impaired drug distribution to tumor cells. We demonstrate the application of these personalized models as tools to rank molecular therapies for the normalization of the tumoroid microenvironment and to discover new therapeutic targets such as IL8 and CD44, which may ultimately improve drug efficacy in breast cancer patients.

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“…Additionally, automation will help increase throughput [ 123 ]. A key improvement to the current models is the introduction of continuous perfusion by integrating micropumps [ 124 ]. Indeed, flow perfusion culture could advance the model in several important aspects.…”

Section: Remaining Challenges In Modeling Response To Cell Therapiesmentioning

confidence: 99%

Engineered Microphysiological Systems for Testing Effectiveness of Cell-Based Cancer Immunotherapies

Shelton

Chen

Kamm

et al. 2022

Cancers

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Cell therapies, including adoptive immune cell therapies and genetically engineered chimeric antigen receptor (CAR) T or NK cells, have shown promise in treating hematologic malignancies. Yet, immune cell infiltration and expansion has proven challenging in solid tumors due to immune cell exclusion and exhaustion and the presence of vascular barriers. Testing next-generation immune therapies remains challenging in animals, motivating sophisticated ex vivo models of human tumor biology and prognostic assays to predict treatment response in real-time while comprehensively recapitulating the human tumor immune microenvironment (TIME). This review examines current strategies for testing cell-based cancer immunotherapies using ex vivo microphysiological systems and microfluidic technologies. Insights into the multicellular interactions of the TIME will identify novel therapeutic strategies to help patients whose tumors are refractory or resistant to current immunotherapies. Altogether, these microphysiological systems (MPS) have the capability to predict therapeutic vulnerabilities and biological barriers while studying immune cell infiltration and killing in a more physiologically relevant context, thereby providing important insights into fundamental biologic mechanisms to expand our understanding of and treatments for currently incurable malignancies.

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Microheart: A microfluidic pump for functional vascular culture in microphysiological systems

Cited by 25 publications

References 30 publications

A predictive microfluidic model of human glioblastoma to assess trafficking of blood–brain barrier-penetrant nanoparticles

A predictive microfluidic model of human glioblastoma to assess trafficking of blood–brain barrier-penetrant nanoparticles

Personalized models of breast cancer desmoplasia reveal biomechanical determinants of drug penetration

Engineered Microphysiological Systems for Testing Effectiveness of Cell-Based Cancer Immunotherapies

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