- 著者
- Anna K. Kopec Ryuji Yokokawa Nasir Khan Ikuo Horii James E. Finley Christine P. Bono Carol Donovan Jessica Roy Julie Harney Andrew D. Burdick Bart Jessen Shuyan Lu Mark Collinge Ramin Banan Sadeghian Mazin Derzi Lindsay Tomlinson John E. Burkhardt
- 出版者
- The Japanese Society of Toxicology
- 雑誌
- The Journal of Toxicological Sciences (ISSN:03881350)
- 巻号頁・発行日
- vol.46, no.3, pp.99-114, 2021 (Released:2021-03-01)
- 参考文献数
- 68
- 被引用文献数
- 1 18
Microphysiological systems (MPS) are making advances to provide more standardized and predictive physiologically relevant responses to test articles in living tissues and organ systems. The excitement surrounding the potential of MPS to better predict human responses to medicines and improving clinical translation is overshadowed by their relatively slow adoption by the pharmaceutical industry and regulators. Collaboration between multiorganizational consortia and regulators is necessary to build an understanding of the strengths and limitations of MPS models and closing the current gaps. Here, we review some of the advances in MPS research, focusing on liver, intestine, vascular system, kidney and lung and present examples highlighting the context of use for these systems. For MPS to gain a foothold in drug development, they must have added value over existing approaches. Ideally, the application of MPS will augment in vivo studies and reduce the use of animals via tiered screening with less reliance on exploratory toxicology studies to screen compounds. Because MPS support multiple cell types (e.g. primary or stem-cell derived cells) and organ systems, identifying when MPS are more appropriate than simple 2D in vitro models for understanding physiological responses to test articles is necessary. Once identified, MPS models require qualification for that specific context of use and must be reproducible to allow future validation. Ultimately, the challenges of balancing complexity with reproducibility will inform the promise of advancing the MPS field and are critical for realization of the goal to reduce, refine and replace (3Rs) the use of animals in nonclinical research.
- 著者
- 髙田 裕司 上野 遼平 Ramin Banan Sadeghian 永沼 香織 辻 清孝 藤本 和也 横川 隆司
- 出版者
- 一般社団法人 電気学会
- 雑誌
- 電気学会論文誌E(センサ・マイクロマシン部門誌) (ISSN:13418939)
- 巻号頁・発行日
- vol.142, no.2, pp.21-28, 2022-02-01 (Released:2022-02-01)
- 参考文献数
- 14
- 被引用文献数
- 1
We developed a bi-channel microfluidic device integrated with a four-probe electrode system to measure the trans-epithelial electrical resistance (TEER). Time course of TEER was monitored when the extracellular Ca2+ was removed and replenished both from the upper and lower channels. We showed that tight junctions were disrupted rapidly once Ca2+ was removed from the basal side. However, when Ca2+ was removed from the apical side such disruption progressed slowly. Upon replenishing Ca2+ content at the basal side the TEER recovery pace was also faster than the case of replenishing it at the apical side. We conclude that cell polarity needs to be taken into account during the process of Ca2+ removal/replacement in explaining the dynamics of tight junction disruption/recovery. These results indicate that our approach can be utilized in detecting cell polarity in real time and low invasion.