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Change of heart

In vitro assays that predict in vivo adverse phenotypes emerging in vivo late in drug development are critical for avoiding drug attrition. The challenge is that cells isolated in the dish and molecules isolated in the test tube often have changed their nature or even their composition in their new environment and may behave very differently than they do in the body.

Induced pluripotent stem cells (iPSC) are a relatively new technology emerging from many years of basic science research in stem cell and developmental biology. iPSC are stem cells that are harvested from organs that are cultured to retain the same character as they have in vivo. For example, iPSC harvested from the heart of an individual with a congenital arrhythmia will beat at the same rate and in the same pattern as the individuals intact heart, including mirroring the defect in the heartbeat.

Recently, a group harnessed iPSC cells to develop an in vitro assay for heart (cardiac) cell contraction, which is a frequent effect of drugs that leads to their failure in clinical trials. The group utilized a more complex form of iPSC, namely organoid formation, which they call microtissues. These are a step further from iPSC in that they are a complex assembly of several different cell types recapitulating a more complex function of the parent organ. In this case the microtissues had a “heartbeat,” uniform size and the same molecular makeup as contractile tissues in the adult heart. The investigators showed that instrumentation could detect a variety of complex contractility phenotypes observed in vivo.

GeneCentrix’ tools assess drug target expression in all the major body tissues independently, possibly unveiling other tissues that may be amenable to iPSC or microtissue assay development to fight drug attrition.

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