Patient-Specific Vascularized Tumor Model: Blocking TAM Recruitment with Multispecific Antibodies Targeting CCR2 and CSF-1R DOI Creative Commons
Huu Tuan Nguyen,

Nadia Gurvich,

Mark R. Gillrie

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Ноя. 29, 2023

Tumor-associated inflammation drives cancer progression and therapy resistance, with the infiltration of monocyte-derived tumor-associated macrophages (TAMs) associated poor prognosis in diverse cancers. Targeting TAMs holds potential against solid tumors, but effective immunotherapies require testing on immunocompetent human models prior to clinical trials. Here, we develop an vitro model microvascular networks that incorporates tumor spheroids or patient tissues. By perfusing vasculature monocytes, investigate monocyte trafficking into evaluate targeting microenvironment. Our findings demonstrate vascularized breast lung can enhance recruitment via TAM-produced CCL7 CCL2, mediated by CSF-1R. Additionally, assess a novel multispecific antibody CCR2, CSF-1R, neutralizing TGF-β, referred as CSF1R/CCR2/TGF-β Ab, monocytes using our 3D models. This repolarizes towards anti-tumoral M1-like phenotype, reduces chemoattractant protein secretion, effectively blocks migration. Finally, show Ab inhibits patient-specific Overall, this offers valuable insights enables functional innovative therapeutic antibodies microenvironment (TME).

Язык: Английский

Patient-Specific Vascularized Tumor Model: Blocking TAM Recruitment with Multispecific Antibodies Targeting CCR2 and CSF-1R DOI
Huu Tuan Nguyen,

Ellen L. Kan,

Mouhita Humayun

и другие.

Biomaterials, Год журнала: 2024, Номер 312, С. 122731 - 122731

Опубликована: Июль 30, 2024

Язык: Английский

Процитировано

9
Personalized Vascularized Models of Breast Cancer Desmoplasia Reveal Biomechanical Determinants of Drug Delivery to the Tumor DOI Creative Commons
Giovanni S. Offeddu, Elena Cambria, Sarah E. Shelton

и другие.

Advanced Science, Год журнала: 2024, Номер 11(38)

Опубликована: Июль 23, 2024

Desmoplasia in breast cancer leads to heterogeneity physical properties of the tissue, resulting disparities drug delivery and treatment efficacy among patients, thus contributing high disease mortality. Personalized vitro models hold great promise for high-throughput testing therapeutic strategies normalize aberrant microenvironment a patient-specific manner. Here, tumoroids assembled from cell lines (MCF7, SKBR3, MDA-MB-468) patient-derived tumor cells (TCs) cultured microphysiological systems including perfusable microvasculature reproduce key aspects stromal vascular dysfunction causing impaired delivery. Models containing SKBR3 MDA-MB-468 show higher hyaluronic acid (HA) deposition, permeability, interstitial fluid pressure (IFP), degradation HA relative MCF7 or without tumoroids. Interleukin 8 (IL8) secretion is found responsible loss HA. Interventions targeting IL8 perfusion, IFP, ultimately enhance TC death response perfusion with trastuzumab cetuximab. Similar responses are observed models. These can be personalized by using applied discover new molecular therapies normalization microenvironment.

Язык: Английский

Процитировано

6
Myofibroblasts reduce angiogenesis and vasculogenesis in a vascularized microphysiological model of lung fibrosis DOI Creative Commons
Elena Cambria, Adriana Blazeski, Eunkyung Ko

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Янв. 14, 2025

Abstract Lung fibrosis, characterized by chronic and progressive scarring, has no cure. Hallmarks are the accumulation of myofibroblasts extracellular matrix, as well vascular remodeling. The crosstalk between vasculature is poorly understood, with conflicting reports on whether angiogenesis vessel density increased or decreased in lung fibrosis. We developed a microphysiological system that recapitulates pathophysiology fibrosis disentangles myofibroblast-vascular interactions. maintained their phenotype 3D without exogenous TGF-β displayed anti-angiogenic anti-vasculogenic activities when cultured endothelial cells microfluidic device. These effects, including sprouting, altered morphology, permeability, were mediated TGF-β1 reduced VEGF secretion. Pharmacological interventions targeting these cytokines restored morphology demonstrating potential this model to screen anti-fibrotic drugs. This provides insights into offers platform for therapeutic development.

Язык: Английский

Процитировано

0
A Cost-Effective and Easy to Assemble 3D Human Microchannel Blood–Brain Barrier Model and Its Application in Tumor Cell Adhesion Under Flow DOI Creative Commons

Yunfei Li,

Bingmei M. Fu

Cells, Год журнала: 2025, Номер 14(6), С. 456 - 456

Опубликована: Март 19, 2025

By utilizing polydimethylsiloxane (PDMS), collagen hydrogel, and a cell line for human cerebral microvascular endothelial cells, we produced 3D microchannel blood–brain barrier (BBB) model under physiological flow. This BBB has circular-shaped cross-section diameter of ~100 μm, which can properly mimic the microvessel responsible material exchange between circulating blood brain tissue. The permeability to small molecule (sodium fluorescein with molecular weight 376) that large (Dex-70k) are same as those rat microvessels. replicate effects plasma protein, orosomucoid, cytokine, vascular growth factor (VEGF), an enzyme, heparinase III, on either or mesenteric microvessesels in terms modulation glycocalyx (heparan sulfate). It also adhesion breast cancer cell, MDA-MB-231, microvessels no treatment treatments VEGF, III. Because difficulties accessing microvessels, this inexpensive easy assemble be applied investigate BBB-modulating mechanisms health disease develop therapeutic interventions targeting tumor metastasis brain.

Язык: Английский

Процитировано

0
Conversation before crossing: dissecting metastatic tumor-vascular interactions in microphysiological systems DOI
Lakyn Mayo, Matthew L. Kutys

AJP Cell Physiology, Год журнала: 2022, Номер 323(5), С. C1333 - C1344

Опубликована: Сен. 19, 2022

Tumor metastasis via the circulation requires crossing vascular barrier twice: first, during intravasation when tumor cells disseminate from primary site through proximal vasculature, and second, extravasation, exit to form distant metastatic seeds. During these key events, chemomechanical signaling between endothelial elicits reciprocal changes in cell morphology behavior that are necessary breach vessel wall. Existing experimental systems have provided a limited understanding of diverse mechanisms underlying tumor-endothelial interactions extravasation. Recent advances microphysiological revolutionized ability generate miniaturized human tissues with tailored three-dimensional architectures, physiological interfaces, precise chemical physical microenvironments. By doing so, enable access complex morphogenic processes associated progression unprecedented resolution biological control. Here, we discuss recent examples which been leveraged reveal new mechanistic insight into cellular molecular control operating at interface

Язык: Английский

Процитировано

3
Patient-Specific Vascularized Tumor Model: Blocking TAM Recruitment with Multispecific Antibodies Targeting CCR2 and CSF-1R DOI Creative Commons
Huu Tuan Nguyen,

Nadia Gurvich,

Mark R. Gillrie

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Ноя. 29, 2023

Tumor-associated inflammation drives cancer progression and therapy resistance, with the infiltration of monocyte-derived tumor-associated macrophages (TAMs) associated poor prognosis in diverse cancers. Targeting TAMs holds potential against solid tumors, but effective immunotherapies require testing on immunocompetent human models prior to clinical trials. Here, we develop an vitro model microvascular networks that incorporates tumor spheroids or patient tissues. By perfusing vasculature monocytes, investigate monocyte trafficking into evaluate targeting microenvironment. Our findings demonstrate vascularized breast lung can enhance recruitment via TAM-produced CCL7 CCL2, mediated by CSF-1R. Additionally, assess a novel multispecific antibody CCR2, CSF-1R, neutralizing TGF-β, referred as CSF1R/CCR2/TGF-β Ab, monocytes using our 3D models. This repolarizes towards anti-tumoral M1-like phenotype, reduces chemoattractant protein secretion, effectively blocks migration. Finally, show Ab inhibits patient-specific Overall, this offers valuable insights enables functional innovative therapeutic antibodies microenvironment (TME).

Язык: Английский

Процитировано

1