Cellular microfluidic technologies for biomodeling of pathological processes

Author(s):  
А.Н. Мыльникова ◽  
Д.В. Колесов ◽  
А.А. Московцев ◽  
А.А. Соколовская ◽  
В.А. Юркив ◽  
...  

Стремительный технический прогресс способствует появлению все новых подходов в клеточной биологии, одним из них является клеточная микрофлюидика. Применение технологий микрофлюидики открыло новые возможности по культивированию, прецизионному анализу и манипулированию как популяциями клеток, так и отдельными клетками. Основой новой технологии является микрофлюидный чип - миниатюрное устройство, содержащее систему микро- и наноканалов, полостей, мембран и других элементов. Возможность прецизионного управления пространственным расположением клеток и их микроокружением предоставляет уникальные и беспрецедентные возможности для биомоделирования in vitro фунциональных элементов органов и тканей. В данном обзоре приведены примеры построения и применения таких трехмерных микрофлюидных клеточных моделей для анализа протекающих в них физиологических и патологических процессов. Особое внимание уделено влиянию клеточного микроокружения клетки на её функционирование. Significant technological progress has brought new approaches to cell biology. Using microfluidic technologies has opened new opportunities for cultivation, analysis, and manipulation of both individual cells and their populations. The basis of the new technology is a microfluidic chip, a miniature device containing a system of micro- and nanochannels, cavities, membranes, and other elements. The precise control of spatial arrangement of cells and their microenvironment opens new prospects for in vitro biomodeling of functional elements of organs and tissues. This review shows examples for construction and application of such three-dimensional microfluidic cellular models for analysis of physiological and pathological processes. Particular attention is paid to the influence of cellular microenvironment on cell functioning.

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 930
Author(s):  
Donatella Delle Cave ◽  
Riccardo Rizzo ◽  
Bruno Sainz ◽  
Giuseppe Gigli ◽  
Loretta L. del Mercato ◽  
...  

Pancreatic cancer, the fourth most common cancer worldwide, shows a highly unsuccessful therapeutic response. In the last 10 years, neither important advancements nor new therapeutic strategies have significantly impacted patient survival, highlighting the need to pursue new avenues for drug development discovery and design. Advanced cellular models, resembling as much as possible the original in vivo tumor environment, may be more successful in predicting the efficacy of future anti-cancer candidates in clinical trials. In this review, we discuss novel bioengineered platforms for anticancer drug discovery in pancreatic cancer, from traditional two-dimensional models to innovative three-dimensional ones.


Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 596
Author(s):  
Christian Jorgensen ◽  
Matthieu Simon

Joint-on-a-chip is a new technology able to replicate the joint functions into microscale systems close to pathophysiological conditions. Recent advances in 3D printing techniques allow the precise control of the architecture of the cellular compartments (including chondrocytes, stromal cells, osteocytes and synoviocytes). These tools integrate fluid circulation, the delivery of growth factors, physical stimulation including oxygen level, external pressure, and mobility. All of these structures must be able to mimic the specific functions of the diarthrodial joint: mobility, biomechanical aspects and cellular interactions. All the elements must be grouped together in space and reorganized in a manner close to the joint organ. This will allow the study of rheumatic disease physiopathology, the development of biomarkers and the screening of new drugs.


Tumor Biology ◽  
2010 ◽  
Vol 32 (3) ◽  
pp. 469-479 ◽  
Author(s):  
Jianhua Tang ◽  
Jiefeng Cui ◽  
Rongxin Chen ◽  
Kun Guo ◽  
Xiaonan Kang ◽  
...  

2020 ◽  
Vol 21 (17) ◽  
pp. 6225 ◽  
Author(s):  
Kamila Białkowska ◽  
Piotr Komorowski ◽  
Maria Bryszewska ◽  
Katarzyna Miłowska

Cell cultures are very important for testing materials and drugs, and in the examination of cell biology and special cell mechanisms. The most popular models of cell culture are two-dimensional (2D) as monolayers, but this does not mimic the natural cell environment. Cells are mostly deprived of cell–cell and cell–extracellular matrix interactions. A much better in vitro model is three-dimensional (3D) culture. Because many cell lines have the ability to self-assemble, one 3D culturing method is to produce spheroids. There are several systems for culturing cells in spheroids, e.g., hanging drop, scaffolds and hydrogels, and these cultures have their applications in drug and nanoparticles testing, and disease modeling. In this paper we would like to present methods of preparation of spheroids in general and emphasize the most important applications.


2021 ◽  
Vol 1 (1) ◽  
Author(s):  
Minjin Jeong ◽  
Karen E. Ocwieja ◽  
Dongjun Han ◽  
P. Ashley Wackym ◽  
Yichen Zhang ◽  
...  

Abstract Background COVID-19 is a pandemic respiratory and vascular disease caused by SARS-CoV-2 virus. There is a growing number of sensory deficits associated with COVID-19 and molecular mechanisms underlying these deficits are incompletely understood. Methods We report a series of ten COVID-19 patients with audiovestibular symptoms such as hearing loss, vestibular dysfunction and tinnitus. To investigate the causal relationship between SARS-CoV-2 and audiovestibular dysfunction, we examine human inner ear tissue, human inner ear in vitro cellular models, and mouse inner ear tissue. Results We demonstrate that adult human inner ear tissue co-expresses the angiotensin-converting enzyme 2 (ACE2) receptor for SARS-CoV-2 virus, and the transmembrane protease serine 2 (TMPRSS2) and FURIN cofactors required for virus entry. Furthermore, hair cells and Schwann cells in explanted human vestibular tissue can be infected by SARS-CoV-2, as demonstrated by confocal microscopy. We establish three human induced pluripotent stem cell (hiPSC)-derived in vitro models of the inner ear for infection: two-dimensional otic prosensory cells (OPCs) and Schwann cell precursors (SCPs), and three-dimensional inner ear organoids. Both OPCs and SCPs express ACE2, TMPRSS2, and FURIN, with lower ACE2 and FURIN expression in SCPs. OPCs are permissive to SARS-CoV-2 infection; lower infection rates exist in isogenic SCPs. The inner ear organoids show that hair cells express ACE2 and are targets for SARS-CoV-2. Conclusions Our results provide mechanistic explanations of audiovestibular dysfunction in COVID-19 patients and introduce hiPSC-derived systems for studying infectious human otologic disease.


The Analyst ◽  
2020 ◽  
Vol 145 (21) ◽  
pp. 6937-6947
Author(s):  
Magdalena Flont ◽  
Elżbieta Jastrzębska ◽  
Zbigniew Brzózka

Three-dimensional (3D) cellular models of cancer tissue are necessary tools to analyze new anticancer drugs under in vitro conditions.


2000 ◽  
Vol 89 (6) ◽  
pp. 2508-2517 ◽  
Author(s):  
T. J. Goodwin ◽  
L. Coate-Li ◽  
R. M. Linnehan ◽  
T. G. Hammond

This study established two- and three-dimensional renal proximal tubular cell cultures of the endangered species bowhead whale ( Balaena mysticetus), developed SV40-transfected cultures, and cloned the 61-amino acid open reading frame for the metallothionein protein, the primary binding site for heavy metal contamination in mammals. Microgravity research, modulations in mechanical culture conditions (modeled microgravity), and shear stress have spawned innovative approaches to understanding the dynamics of cellular interactions, gene expression, and differentiation in several cellular systems. These investigations have led to the creation of ex vivo tissue models capable of serving as physiological research analogs for three-dimensional cellular interactions. These models are enabling studies in immune function, tissue modeling for basic research, and neoplasia. Three-dimensional cellular models emulate aspects of in vivo cellular architecture and physiology and may facilitate environmental toxicological studies aimed at elucidating biological functions and responses at the cellular level. Marine mammals occupy a significant ecological niche (72% of the Earth's surface is water) in terms of the potential for information on bioaccumulation and transport of terrestrial and marine environmental toxins in high-order vertebrates. Few ex vivo models of marine mammal physiology exist in vitro to accomplish the aforementioned studies. Techniques developed in this investigation, based on previous tissue modeling successes, may serve to facilitate similar research in other marine mammals.


2005 ◽  
Vol 192 (1) ◽  
pp. 1-6 ◽  
Author(s):  
David B. Edelman ◽  
Edward W. Keefer

2021 ◽  
Vol 22 (2) ◽  
pp. 830
Author(s):  
Georgia Pennarossa ◽  
Sharon Arcuri ◽  
Teresina De Iorio ◽  
Fulvio Gandolfi ◽  
Tiziana A. L. Brevini

Bi-dimensional culture systems have represented the most used method to study cell biology outside the body for over a century. Although they convey useful information, such systems may lose tissue-specific architecture, biomechanical effectors, and biochemical cues deriving from the native extracellular matrix, with significant alterations in several cellular functions and processes. Notably, the introduction of three-dimensional (3D) platforms that are able to re-create in vitro the structures of the native tissue, have overcome some of these issues, since they better mimic the in vivo milieu and reduce the gap between the cell culture ambient and the tissue environment. 3D culture systems are currently used in a broad range of studies, from cancer and stem cell biology, to drug testing and discovery. Here, we describe the mechanisms used by cells to perceive and respond to biomechanical cues and the main signaling pathways involved. We provide an overall perspective of the most recent 3D technologies. Given the breadth of the subject, we concentrate on the use of hydrogels, bioreactors, 3D printing and bioprinting, nanofiber-based scaffolds, and preparation of a decellularized bio-matrix. In addition, we report the possibility to combine the use of 3D cultures with functionalized nanoparticles to obtain highly predictive in vitro models for use in the nanomedicine field.


2021 ◽  
Vol 22 (3) ◽  
pp. 1195
Author(s):  
Giada Bassi ◽  
Maria Aurora Grimaudo ◽  
Silvia Panseri ◽  
Monica Montesi

A hot topic in biomedical science is the implementation of more predictive in vitro models of human tissues to significantly improve the knowledge of physiological or pathological process, drugs discovery and screening. Bidimensional (2D) culture systems still represent good high-throughput options for basic research. Unfortunately, these systems are not able to recapitulate the in vivo three-dimensional (3D) environment of native tissues, resulting in a poor in vitro–in vivo translation. In addition, intra-species differences limited the use of animal data for predicting human responses, increasing in vivo preclinical failures and ethical concerns. Dealing with these challenges, in vitro 3D technological approaches were recently bioengineered as promising platforms able to closely capture the complexity of in vivo normal/pathological tissues. Potentially, such systems could resemble tissue-specific extracellular matrix (ECM), cell–cell and cell–ECM interactions and specific cell biological responses to mechanical and physical/chemical properties of the matrix. In this context, this review presents the state of the art of the most advanced progresses of the last years. A special attention to the emerging technologies for the development of human 3D disease-relevant and physiological models, varying from cell self-assembly (i.e., multicellular spheroids and organoids) to the use of biomaterials and microfluidic devices has been given.


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