scholarly journals The Tumor-on-Chip: Recent Advances in the Development of Microfluidic Systems to Recapitulate the Physiology of Solid Tumors

Materials ◽  
2019 ◽  
Vol 12 (18) ◽  
pp. 2945 ◽  
Author(s):  
Grissel Trujillo-de Santiago ◽  
Brenda Giselle Flores-Garza ◽  
Jorge Alfonso Tavares-Negrete ◽  
Itzel Montserrat Lara-Mayorga ◽  
Ivonne González-Gamboa ◽  
...  

The ideal in vitro recreation of the micro-tumor niche—although much needed for a better understanding of cancer etiology and development of better anticancer therapies—is highly challenging. Tumors are complex three-dimensional (3D) tissues that establish a dynamic cross-talk with the surrounding tissues through complex chemical signaling. An extensive body of experimental evidence has established that 3D culture systems more closely recapitulate the architecture and the physiology of human solid tumors when compared with traditional 2D systems. Moreover, conventional 3D culture systems fail to recreate the dynamics of the tumor niche. Tumor-on-chip systems, which are microfluidic devices that aim to recreate relevant features of the tumor physiology, have recently emerged as powerful tools in cancer research. In tumor-on-chip systems, the use of microfluidics adds another dimension of physiological mimicry by allowing a continuous feed of nutrients (and pharmaceutical compounds). Here, we discuss recently published literature related to the culture of solid tumor-like tissues in microfluidic systems (tumor-on-chip devices). Our aim is to provide the readers with an overview of the state of the art on this particular theme and to illustrate the toolbox available today for engineering tumor-like structures (and their environments) in microfluidic devices. The suitability of tumor-on-chip devices is increasing in many areas of cancer research, including the study of the physiology of solid tumors, the screening of novel anticancer pharmaceutical compounds before resourcing to animal models, and the development of personalized treatments. In the years to come, additive manufacturing (3D bioprinting and 3D printing), computational fluid dynamics, and medium- to high-throughput omics will become powerful enablers of a new wave of more sophisticated and effective tumor-on-chip devices.

Polymers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 3216
Author(s):  
Simona Argentiere ◽  
Pietro Aleardo Siciliano ◽  
Laura Blasi

The Organ-on-chip (OOC) devices represent the new frontier in biomedical research to produce micro-organoids and tissues for drug testing and regenerative medicine. The development of such miniaturized models requires the 3D culture of multiple cell types in a highly controlled microenvironment, opening new challenges in reproducing the extracellular matrix (ECM) experienced by cells in vivo. In this regard, cell-laden microgels (CLMs) represent a promising tool for 3D cell culturing and on-chip generation of micro-organs. The engineering of hydrogel matrix with properly balanced biochemical and biophysical cues enables the formation of tunable 3D cellular microenvironments and long-term in vitro cultures. This focused review provides an overview of the most recent applications of CLMs in microfluidic devices for organoids formation, highlighting microgels’ roles in OOC development as well as insights into future research.


2018 ◽  
Author(s):  
Fantuzzi Federica ◽  
Toivonen Sanna ◽  
Schiavo Andrea Alex ◽  
Pachera Nathalie ◽  
Rajaei Bahareh ◽  
...  

2021 ◽  
Author(s):  
Mattia Saggioro ◽  
Stefania D'Agostino ◽  
Anna Gallo ◽  
Sara Crotti ◽  
Sara D'Aronco ◽  
...  

Three-dimensional (3D) culture systems are progressively getting attention given their potential in overcoming limitations of the classical 2D in vitro systems. Among different supports for 3D cell culture, hydrogels (HGs)...


Pharmaceutics ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1186
Author(s):  
Bárbara Pinto ◽  
Ana C. Henriques ◽  
Patrícia M. A. Silva ◽  
Hassan Bousbaa

Most cancer biologists still rely on conventional two-dimensional (2D) monolayer culture techniques to test in vitro anti-tumor drugs prior to in vivo testing. However, the vast majority of promising preclinical drugs have no or weak efficacy in real patients with tumors, thereby delaying the discovery of successful therapeutics. This is because 2D culture lacks cell–cell contacts and natural tumor microenvironment, important in tumor signaling and drug response, thereby resulting in a reduced malignant phenotype compared to the real tumor. In this sense, three-dimensional (3D) cultures of cancer cells that better recapitulate in vivo cell environments emerged as scientifically accurate and low cost cancer models for preclinical screening and testing of new drug candidates before moving to expensive and time-consuming animal models. Here, we provide a comprehensive overview of 3D tumor systems and highlight the strategies for spheroid construction and evaluation tools of targeted therapies, focusing on their applicability in cancer research. Examples of the applicability of 3D culture for the evaluation of the therapeutic efficacy of nanomedicines are discussed.


2017 ◽  
Vol 22 (3) ◽  
pp. 245-253 ◽  
Author(s):  
Eliza Li Shan Fong ◽  
Tan Boon Toh ◽  
Hanry Yu ◽  
Edward Kai-Hua Chow

Advances in understanding many of the fundamental mechanisms of cancer progression have led to the development of molecular targeted therapies. While molecular targeted therapeutics continue to improve the outcome for cancer patients, tumor heterogeneity among patients, as well as intratumoral heterogeneity, limits the efficacy of these drugs to specific patient subtypes, as well as contributes to relapse. Thus, there is a need for a more personalized approach toward drug development and diagnosis that takes into account the diversity of cancer patients, as well as the complex milieu of tumor cells within a single patient. Three-dimensional (3D) culture systems paired with patient-derived xenografts or patient-derived organoids may provide a more clinically relevant system to address issues presented by personalized or precision medical approaches. In this review, we cover the current methods available for applying 3D culture systems toward personalized cancer research and drug development, as well as key challenges that must be addressed in order to fully realize the potential of 3D patient-derived culture systems for cancer drug development. Greater implementation of 3D patient-derived culture systems in the cancer research field should accelerate the development of truly personalized medical therapies for cancer patients.


2021 ◽  
Vol 1 ◽  
pp. 62
Author(s):  
Giulia Malaguarnera ◽  
Miriam Graute ◽  
Antoni Homs Corbera

It is difficult to model in vitro the intestine when seeking to include crosstalk with the gut microbiota, immune and neuroendocrine systems. Here we present a roadmap of the current models to facilitate the choice in preclinical and translational research with a focus on gut-on-chip. These micro physiological systems (MPS) are microfluidic devices that recapitulate in vitro the physiology of the intestine. We reviewed the gut-on-chips that had been developed in academia and industries as single chip and that have three main purpose: replicate the intestinal physiology, the intestinal pathological features, and for pharmacological tests.


2005 ◽  
Vol 18 (4) ◽  
pp. 677-681 ◽  
Author(s):  
E. Benzoni ◽  
M.L. Torre ◽  
M. Faustini ◽  
S. Stacchezzini ◽  
F. Cremonesi ◽  
...  

Three-dimensional culture systems in barium alginate capsules can be employed to maintain primary granulosa cells in an undifferentiated state for almost 6 days. This is due to a self-organization of cells in a pseudofollicular structure. The transfection of primary granulosa cells is a necessary condition when employing these culture systems for several purposes, for example as an in vitro toxicity test or the development of oocytes or zygotes. In this work, the feasibility of two transient transfection techniques (liposome-mediated and electroporation) was assessed in primary porcine granulosa cells after a 6-day culture in an artificial extracellular matrix (barium alginate membrane). Human recombinant green fluorescent protein was chosen as a molecular readout, and protein expression was assessed after 48 hours from transfection. Liposome-mediated transfection gave low transfection levels, with increasing yields from 2 to 12 μgDNA/ml of medium; the maximum percentage (85.7%) was reached at 12 μgDNA/ml of medium. Electroporation-mediated transfection yields were higher: the best results (81.7% of transfected cells) were achieved with two 50V pulses and 12 μg/ml DNA. The application of a single or double pulse (50V) at 4 mgDNA/ml gave negligible results. These results indicate that primary granulosa cell cultured in barium alginate capsules can be transfected by electroporation with high transfection yields.


Author(s):  
Hongyu Li ◽  
Lixiong Gao ◽  
Jinlin Du ◽  
Tianju Ma ◽  
Zi Ye ◽  
...  

The genomic profile of animal models is not completely matched with the genomic profile of humans, and 2D cultures do not represent the cellular heterogeneity and tissue architecture found in tissues of their origin. Derived from 3D culture systems, organoids establish a crucial bridge between 2D cell cultures and in vivo animal models. Organoids have wide and promising applications in developmental research, disease modeling, drug screening, precision therapy, and regenerative medicine. However, current organoids represent only single or partial components of a tissue, which lack blood vessels, native microenvironment, communication with near tissues, and a continuous dorsal-ventral axis within 3D culture systems. Although efforts have been made to solve these problems, unfortunately, there is no ideal method. Teratoma, which has been frequently studied in pathological conditions, was recently discovered as a new in vivo model for developmental studies. In contrast to organoids, teratomas have vascularized 3D structures and regions of complex tissue-like organization. Studies have demonstrated that teratomas can be used to mimic multilineage human development, enrich specific somatic progenitor/stem cells, and even generate brain organoids. These results provide unique opportunities to promote our understanding of the vascularization and maturation of organoids. In this review, we first summarize the basic characteristics, applications, and limitations of both organoids and teratomas and further discuss the possibility that in vivo teratoma systems can be used to promote the vascularization and maturation of organoids within an in vitro 3D culture system.


2009 ◽  
Vol 81 (Suppl_1) ◽  
pp. 184-184
Author(s):  
Stefan Schlatt ◽  
Jan-Bernd Stukenborg ◽  
Mahmoud Huleihel ◽  
Joachim Wistuba

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