A novel thin plate spline methodology to model tissue surfaces and quantify tumor cell invasion in organ-on-chip models DOI Creative Commons
Elizabeth Elton, Carly Strelez, Nolan Ung

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 21, 2023

ABSTRACT Organ-on-chip (OOC) models can be useful tools for cancer drug discovery. Advances in OOC technology have led to the development of more complex assays, yet analysis these systems does not always account advancements, resulting technical challenges. A challenging task two-channel microfluidic is define boundary between channels so objects moving within and quantified. We propose a novel imaging-based application thin plate spline method – generalized cubic that used model coordinate transformations tissue compartments quantification invaded objects, representing early steps metastasis. To evaluate its performance, we applied our analytical approach an adapted developed by Emulate, Inc., utilizing system with endothelial cells bottom channel colorectal (CRC) patient-derived organoids (PDOs) top channel. Initial visualization this revealed variations due microscope stage tilt ridge valley-like contours surface. The was functionalized into reproducible process web tool Chip Invasion Contour Analysis (ChICA) surface quantify invading tumor across multiple chips. illustrate applicability method, CRC organoid-chips seeded two different cell types measured distinct surfaces invasion dynamics. Since ChICA utilizes only positional data output from imaging software, applicable agnostic image used. variation introduced manufacturing or during experimental workflow, quickly accurately measure invasion, explore biological mechanisms

Language: Английский

Microphysiological systems as models for immunologically ‘cold’ tumors DOI Creative Commons

Daniela Gaebler,

Stephanie J. Hachey, Christopher C.W. Hughes

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12

Published: April 22, 2024

The tumor microenvironment (TME) is a diverse milieu of cells including cancerous and non-cancerous such as fibroblasts, pericytes, endothelial immune cells. intricate cellular interactions within the TME hold central role in shaping dynamics cancer progression, influencing pivotal aspects initiation, growth, invasion, response to therapeutic interventions, emergence drug resistance. In immunologically 'cold' tumors, marked by scarcity infiltrating cells, limited antigen presentation absence potent immune-stimulating signals, an abundance immunosuppressive factors. While strategies targeting avenue tumors have emerged, there pressing need for novel approaches that faithfully replicate complex non-cellular order develop targeted therapies can effectively stimulate responses improve outcomes patients. Microfluidic devices offer distinct advantages over traditional vitro 3D co-culture models vivo animal models, they better recapitulate key characteristics allow precise, controlled insights into dynamic interplay between various immune, stromal cell types at any timepoint. This review aims underscore microfluidic systems advancing our understanding presents current model aim dissect tumor-stromal, tumor-immune immune-stromal tumors. Understanding intricacies crucial devising effective reinvigorate overcome challenges immunotherapy approaches.

Language: Английский

Citations

4
Lymphoma-on-chip model reveals that lymph node stromal cells promote diffuse large B-cell lymphoma survival and migration DOI Creative Commons
Mohammad Jouybar,

Aleksandra M. Mikula,

Nanouk Zuidmeer

et al.

Materials Today Bio, Journal Year: 2025, Volume and Issue: 31, P. 101544 - 101544

Published: Feb. 7, 2025

Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive non-Hodgkin lymphoma, often developing resistance to current treatments. Development and testing of new therapies hampered by lack good in vivo vitro models mimicking human disease. Here, we developed a lymphoma-on-chip model investigate tumor-supportive roles lymph node stromal cells (LNSCs) - fibroblastic reticular (FRCs) lymphatic endothelial (LECs) DLBCL microenvironment. The includes tubular vessel lined with LECs surrounded hydrogel FRCs. Our findings reveal that FRCs promote survival facilitate tumor cell migration towards vessels. Moreover, demonstrate increase permeability vessels, which further enhanced presence This reveals important role LNSCs progression, offers an innovative tool study microenvironment test potential therapeutic targets improve patient outcomes.

Language: Английский

Citations

0
Ex Vivo Model of Breast Cancer Cell Invasion in Live Lymph Node Tissue DOI Creative Commons
Katerina Morgaenko, Abhinav Arneja,

Alexander G. Ball

et al.

ACS Pharmacology & Translational Science, Journal Year: 2025, Volume and Issue: 8(3), P. 690 - 705

Published: Feb. 10, 2025

Lymph nodes (LNs) are common sites of metastatic invasion in breast cancer, often preceding spread to distant organs and serving as key indicators clinical disease progression. However, the mechanisms cancer cell into LNs not well understood. Existing vivo models struggle isolate specific impacts tumor-draining lymph node (TDLN) milieu on due coevolving relationship between TDLNs upstream tumor. To address these limitations, we used live ex LN tissue slices with intact chemotactic function model within a spatially organized microenvironment. After showing that BRPKp110 cells were chemoattracted factors secreted by naïve 3D migration assay, demonstrated could support seeding, invasion, spread. This novel approach revealed dynamic, preferential anatomical regions LNs, particularly subcapsular sinus (SCS) cortex, chemokine-rich domains immobilized CXCL13 CCL1. While CXCR5 was necessary for portion disruption CXCR5/CXCL13 signaling alone insufficient prevent toward CXCL13-rich domains. Finally, extended this system premetastatic TDLNs, where predicted lower diminished chemokine secretion. In summary, innovative provides platform investigate intricate microenvironment, supporting time-course analysis parallel read-outs. We anticipate will enable further research cancer-immune interactions allow isolation make resistant which is challenging dissect vivo.

Language: Английский

Citations

0
Organ-on-a-Chip Applications in Microfluidic Platforms DOI Creative Commons

Ling An,

Yi Liu, Yaling Liu

et al.

Micromachines, Journal Year: 2025, Volume and Issue: 16(2), P. 201 - 201

Published: Feb. 10, 2025

Microfluidic technology plays a crucial role in organ-on-a-chip (OoC) systems by replicating human physiological processes and disease states, significantly advancing biomedical research drug discovery. This article reviews the design fabrication of microfluidic devices. It also explores how these technologies are integrated into OoC platforms to simulate environments, highlighting key principles, technological advances, diverse applications. Through case studies involving simulation multiple organs such as heart, liver, lungs, evaluates impact systems' on screening, toxicity assessment, personalized medicine. In addition, this considers technical challenges, ethical issues, future directions, looks ahead further optimizing functionality biomimetic precision OoCs through innovation, emphasizing its critical promoting medicine treatment strategies.

Language: Английский

Citations

0
Host-microbe-cancer interactions on-a-chip DOI Creative Commons

Mauricio G. C. Sousa,

Danielle S.K. Brasino, Madeline Krieger

et al.

Frontiers in Bioengineering and Biotechnology, Journal Year: 2025, Volume and Issue: 13

Published: March 31, 2025

The tumor microbiota has emerged as a pivotal contributor to variety of cancers, impacting disease development, progression, and therapeutic resistance. Due the complexity microenvironment, reproducing interactions between microbes, cells, immune system remains great challenge for both in vitro vivo studies. To this end, significant progress been made toward leveraging tumor-on-a-chip model systems replicate critical hallmarks native vitro. These microfluidic platforms offer ability mimic essential components including controllable fluid flow conditions, manipulable extracellular matrix dynamics, intricate 3D multi-cellular communication. primary objective review is discuss recent challenges advances engineering host-microbiota on-a-chip. Ultimately, overcoming these obstacles will help us gain deeper insights into tumor-microbe enhance avenues developing more effective cancer therapies.

Language: Английский

Citations

0
Colorectal cancer: Current status of preclinical research DOI
Edward Agyarko,

Benjamin Tagoe,

Benedicta Obenewaa Dankyi

et al.

Elsevier eBooks, Journal Year: 2025, Volume and Issue: unknown, P. 205 - 229

Published: Jan. 1, 2025

Language: Английский

Citations

0
Immunocompetent Tumor-on-a-Chip: A Translational Tool for Drug Screening and Cancer Therapy DOI

Anqi Liang,

Tao Tao, Jiahui Chen

et al.

Critical Reviews in Oncology/Hematology, Journal Year: 2025, Volume and Issue: unknown, P. 104716 - 104716

Published: April 1, 2025

Language: Английский

Citations

0
Tumor-microenvironment-on-a-chip: the construction and application DOI Creative Commons
Hanzheng Xu,

James J. Wen,

Jiahua Yang

et al.

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: Oct. 23, 2024

Currently, despite the vast amounts of time and money invested in cancer treatment, remains one primary threats to human life. The factor contributing low treatment efficacy is heterogeneity. unclear molecular mechanisms underlying tumorigenesis, coupled with complexity physiology, inability animal models accurately replicate tumor microenvironment, pose significant hurdles development novel therapies. Tumor-microenvironment-on-chip (TMOC) represents a research platform that integrates three-dimensional cell culture microfluidic systems, simulating essential components physiological traits vivo microenvironment. It offers dynamic setting within chip system study progression, potentially heralding breakthrough research. In this review, we will summarize current advancements platform, encompassing various types TMOCs their applications different cancer. From our perspective, TMOC necessitates enhanced integration tissue engineering techniques microphysiological environments before it can evolve into more refined preclinical model for

Language: Английский

Citations

3
Recent advances in micro-physiological systems for investigating tumor metastasis and organotropism DOI
Heejeong Yoon, Jonathan Sabaté del Río,

Seung Woo Cho

et al.

Lab on a Chip, Journal Year: 2024, Volume and Issue: 24(5), P. 1351 - 1366

Published: Jan. 1, 2024

MPS technology holds great potential for studying complex metastasis organotropism. It effectively simulates the dynamic interactions between distinct organ environments and tumor cells, capturing both their inter- intra-tumor heterogeneity.

Language: Английский

Citations

2
Advancement in Cancer Vasculogenesis Modeling through 3D Bioprinting Technology DOI Creative Commons
Arvind Kumar Shukla, Sik Yoon, Sae‐Ock Oh

et al.

Biomimetics, Journal Year: 2024, Volume and Issue: 9(5), P. 306 - 306

Published: May 20, 2024

Cancer vasculogenesis is a pivotal focus of cancer research and treatment given its critical role in tumor development, metastasis, the formation vasculogenic microenvironments. Traditional approaches to investigating face significant challenges accurately modeling intricate Recent advancements three-dimensional (3D) bioprinting technology present promising solutions these challenges. This review provides an overview underscores importance precise modeling. It juxtaposes traditional techniques with 3D technologies, elucidating advantages latter developing models. Furthermore, it explores applications pathological investigations, preclinical medication screening for personalized diagnostics, envisages future prospects bioprinted Despite notable advancements, current have several limitations. Nonetheless, by overcoming technological advances, exhibits immense potential revolutionizing understanding augmenting modalities.

Language: Английский

Citations

2