Engineering a Three-Dimensional In Vitro Drug Testing Platform for Glioblastoma

Author(s):  
Metin Akay ◽  
Duong T. Nguyen ◽  
Yantao Fan ◽  
Yasemin M. Akay

Three-dimensional (3D) in vivo cell culture modeling is quickly emerging as a platform to replace two-dimensional (2D) monolayer cell culture in vitro tests. Three-dimensional tumor models mimic physiological conditions and provide valuable insight of the tumor cell response to drug discovery application. In this study, we used poly(ethylene glycol) (PEG) hydrogel microwells to generate 3D brain cancer spheroids and studied their treatment with anticancer drugs in single or combination treatment. Glioblastoma (GBM) spheroids were grown through 14 days before infecting with two drugs: Pitavastatin and Irinotecan at various concentrations. A significant cell lysis was observed and cell viability decreased to lower than 7% when drugs were combined at the concentration Pitavastatin 10 μM and Irinotecan 50 μM to infect after 7 days. These findings demonstrate a promising platform—PEG hydrogel microwells—that should be an efficient way to test the drug sensitivity in vitro as well as application in different studies.

2021 ◽  
Vol 52 (1) ◽  
Author(s):  
Laurence Finot ◽  
Eric Chanat ◽  
Frederic Dessauge

AbstractIn vivo study of tissue or organ biology in mammals is very complex and progress is slowed by poor accessibility of samples and ethical concerns. Fortunately, however, advances in stem cell identification and culture have made it possible to derive in vitro 3D “tissues” called organoids, these three-dimensional structures partly or fully mimicking the in vivo functioning of organs. The mammary gland produces milk, the source of nutrition for newborn mammals. Milk is synthesized and secreted by the differentiated polarized mammary epithelial cells of the gland. Reconstructing in vitro a mammary-like structure mimicking the functional tissue represents a major challenge in mammary gland biology, especially for farm animals for which specific agronomic questions arise. This would greatly facilitate the study of mammary gland development, milk secretion processes and pathological effects of viral or bacterial infections at the cellular level, all with the objective of improving milk production at the animal level. With this aim, various 3D cell culture models have been developed such as mammospheres and, more recently, efforts to develop organoids in vitro have been considerable. Researchers are now starting to draw inspiration from other fields, such as bioengineering, to generate organoids that would be more physiologically relevant. In this chapter, we will discuss 3D cell culture systems as organoids and their relevance for agronomic research.


2018 ◽  
Vol 47 (3) ◽  
pp. 426-432 ◽  
Author(s):  
Sivan Yogev ◽  
Ayelet Shabtay-Orbach ◽  
Abraham Nyska ◽  
Boaz Mizrahi

Thermoresponsive materials have the ability to respond to a small change in temperature—a property that makes them useful in a wide range of applications and medical devices. Although very promising, there is only little conclusive data about the cytotoxicity and tissue toxicity of these materials. This work studied the biocompatibility of three Food and Drug Administration approved thermoresponsive polymers: poly( N-isopropyl acrylamide), poly(ethylene glycol)-poly(propylene glycol)-poly(ethylene glycol) tri-block copolymer, and poly(lactic acid-co-glycolic acid) and poly(ethylene glycol) tri-block copolymer. Fibroblast NIH 3T3 and HaCaT keratinocyte cells were used for the cytotoxicity testing and a mouse model for the in vivo evaluation. In vivo results generally showed similar trends as the results seen in vitro, with all tested materials presenting a satisfactory biocompatibility in vivo. pNIPAM, however, showed the highest toxicity both in vitro and in vivo, which was explained by the release of harmful monomers and impurities. More data focusing on the biocompatibility of novel thermoresponsive biomaterials will facilitate the use of existing and future medical devices.


Biomaterials ◽  
2004 ◽  
Vol 25 (2) ◽  
pp. 247-258 ◽  
Author(s):  
A.A. Deschamps ◽  
A.A. van Apeldoorn ◽  
H. Hayen ◽  
J.D. de Bruijn ◽  
U. Karst ◽  
...  

2007 ◽  
Vol 341 (1-2) ◽  
pp. 50-57 ◽  
Author(s):  
Hoo-Kyun Choi ◽  
Myung-Kwan Chun ◽  
Se Hee Lee ◽  
Mee Hee Jang ◽  
Hee Doo Kim ◽  
...  

1994 ◽  
Vol 5 (4) ◽  
pp. 283-286 ◽  
Author(s):  
Yoh Kodera ◽  
Taichi Sekine ◽  
Tohru Yasukohchi ◽  
Yoshihiro Kiriu ◽  
Misao Hiroto ◽  
...  

1999 ◽  
Vol 8 (3) ◽  
pp. 293-306 ◽  
Author(s):  
Gregory M. Cruise ◽  
Orion D. Hegre ◽  
Francis V. Lamberti ◽  
Steven R. Hager ◽  
Ron Hill ◽  
...  

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