reproductive tract. Cancer metastasis, tumour metastasis, and physiology are addi-

tional important topics being studied with human organs on a chip. Clinically

relevant in vitro parameters and effects must be correlated with chip measurements

to maximize the utility of ‘human-on-a-chip’ testing. During drug development, this

will also create a link between conventional cultured cells and non-animal clinical

testing techniques.

6.10

Organ-on-a-Chip for Personalized Medicine

The scarcity of adequately predictive preclinical models of human origin is one

factor contributing to the pharmaceutical industry’s high attrition rate. The invention

of human (induced) pluripotent stem cells (hPSCs) and their ability to distinguish

into a range of cell types have sparked interest in developing more stable in vitro

models, as well as for further investigation of their potential in personalized medi-

cine. Extensive testing has revealed great promise for these models. For example,

hepatocytes derived from hPSCs exhibited phospholipidosis and steatosis after

14 days of exposure to hepatotoxic compounds, both of which are indicative of

chronic long-term toxicity. Another example is the production of functional neuronal

cells from induced pluripotent stem cells and their application in Alzheimer’s and

epilepsy research. Investigators have also been able to investigate new therapeutic

options for autosomal dominant-negative diseases, which is a big step forward. This

was demonstrated elegantly by using RNA interference (RNAi) to rescue the

diseased phenotype of hPSC-derived cardiomyocytes carrying a long QT syndrome

mutation or a phospholamban mutation causing either dilated or arrhythmogenic

cardiomyopathy.

The goal of personalized medicine is to determine the optimal medication and

dosage for each patient. Because traditional methods are inefficient or time-

consuming, they are unsuitable for this task. However, using patient samples, the

physical-biological features of each patient’s disease can be reproduced in an ‘organ-

on-a-chip’. The cells can be extracted directly from the patient’s biological fluids and

cultured on the microfluidic device before being exposed to various drug dosages.

To reveal the cell types to the drugs in a manner consistent with their natural

microenvironment, the medication should be mixed with blood. Other critical

tissue-related variables, such as oxygenation, motion, and flow behaviour, can be

altered in response to health data to design the physiological, structural, and chemi-

cal micro-environment around the cells. The ‘organ-on-a-chip’ technology, as an

in vitro model, connects translational and reverse translational research for the

advancement of personalized medicine (Fig. 6.4).

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G. Aggarwal et al.