utilization-microscale-silicon-cantilevers-to-assess-cellular

Utilization of Microscale Silicon Cantilevers to Assess Cellular Contractile Function <em>In Vitro</em>

The development of more predictive and biologically relevant in vitro assays is predicated on the advancement of versatile cell culture systems which ...

University of Central Florida

Multi-organ microdevices can mimic tissue-tissue interactions that occur as a result of metabolite travel from one tissue to other tissues in vitro. These systems are capable of simulating human metabolism, including the conversion of a pro-drug to its effective metabolite as well as its subsequent therapeutic actions and toxic side effects. Since tissue-tissue interactions in the human body can play a significant role in determining the success of new pharmaceuticals, the development and use of multi-organ microdevices present an opportunity to improve the drug development process. The devices have the potential to predict potential toxic side effects with higher accuracy before a drug enters the expensive phase of clinical trials as well as to estimate efficacy and dose response. Multi-organ microdevices also have the potential to aid in the development of new therapeutic strategies by providing a platform for testing in the context of human metabolism (as opposed to animal models). Further, when operated with human biopsy samples, the devices could be a gateway for the development of individualized medicine. Here we review studies in which multi-organ microdevices have been developed and used in a ways that demonstrate how the devices' capabilities can present unique opportunities for the study of drug action. We will also discuss challenges that are inherent in the development of multi-organ microdevices. Among these are how to design the devices, and how to create devices that mimic the human metabolism with high authenticity. Since single organ devices are testing platforms for tissues that can later be combined with other tissues within multi-organ devices, we will also mention single organ devices where appropriate in the discussion.

How multi-organ microdevices can help foster drug development.

A multiorgan, functional, human in vitro assay system or 'Body-on-a-Chip' would be of tremendous benefit to the drug discovery and toxicology industries, as well as providing a more biologically accurate model for the study of disease as well as applied and basic biological research. Here, we describe the advances our team has made towards this goal, as well as the most pertinent issues facing further development of these systems. Description is given of individual organ models with appropriate cellular functionality, and our efforts to produce human iterations of each using primary and stem cell sources for eventual incorporation into this system. Advancement of the 'Body-on-a-Chip' field is predicated on the availability of abundant sources of human cells, capable of full differentiation and maturation to adult phenotypes, for which researchers are largely dependent on stem cells. Although this level of maturation is not yet achievable in all cell types, the work of our group highlights the high level of functionality that can be achieved using current technology, for a wide variety of cell types. As availability of functional human cell types for in vitro culture increases, the potential to produce a multiorgan in vitro system capable of accurately reproducing acute and chronic human responses to chemical and pathological challenge in real time will also increase.

Article	Year
How multi-organ microdevices can help foster drug development. Advanced drug delivery reviews\| PubMed ID: 24412641	2014
Microphysiological systems and low-cost microfluidic platform with analytics. Stem cell research & therapy\| PubMed ID: 24565109	2013

Alec S.T. Smith

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