A pharmaceutical industry perspective on microphysiological kidney systems for evaluation of safety for new therapies
| Autor: | Jean-Charles Gautier, Myrtle Davis, Douglas A. Keller, Niresh Hariparsad, Jonathan A. Phillips, Radhakrishna Sura, Taraka Sai Pavan Grandhi, Terry R. Van Vleet |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Drug Industry Drug Evaluation Preclinical Biomedical Engineering Bioengineering Kidney Models Biological Biochemistry 03 medical and health sciences 0302 clinical medicine Drug Development Lab-On-A-Chip Devices Humans Safety testing Pharmaceutical industry ADME urogenital system business.industry Human kidney General Chemistry Microfluidic Analytical Techniques 030104 developmental biology Pharmaceutical Preparations Drug development Risk analysis (engineering) 030220 oncology & carcinogenesis business |
| Zdroj: | Lab on a Chip. 20:468-476 |
| ISSN: | 1473-0189 1473-0197 |
| DOI: | 10.1039/c9lc00925f |
| Popis: | The human kidney contains approximately one million nephrons. As the functional unit of the kidney, the nephron affords an opportunity to approximate the kidney at a microphysiological scale. Recent emergence of physiologically accurate human tissue models has radically advanced the possibilities of mimicking organ biology and multi-organ combinations in vitro. Anatomically, the nephron is one of the most complex, sequentially integrated microfluidic units in the body making the miniaturized microfluidic systems excellent candidates for capturing the kidney biology in vitro. While these models are promising, there are a number of considerations for practical implementation into a drug development paradigm. Opportunities for pharmaceutical industry applications of new MPS models often start with drug safety testing. As such, the intent of this article is to focus on safety and ADME applications. This article reviews biological functions of the kidney and options for characterizing known roles in nephrotoxicity. The concept of "context-of-use" is introduced as a framework for describing and verifying the specific features of an MPS platform for use in drug development. Overall, we present a perspective on key attributes of microphysiological kidney models, which the pharmaceutical industry could leverage to improve confident safety and ADME evaluations of experimental therapies. |
| Databáze: | OpenAIRE |
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