iPS technology: Four factors that will change the world… some day
Although they haven’t yet fulfilled their promises in therapeutics, iPS cells are now routinely used in an arm-long list of disciplines, including developmental and regenerative biology, neuroscience, cardiology, hepatology, disease-modeling, and even drug discovery. This technology has allowed major advances in the elucidation of pathological mechanisms of numerous diseases such as Alzheimer’s and Parkinson’s.
Many efforts have been concentrated toward differentiating human iPS cells obtained from healthy donors or patients into specialized cell types, including hepatocytes or cardiomyocytes to test new drugs’ toxicity. This might even become the norm in drug safety assessment one day, with the CiPA (Comprehensive in vitro Proarrhythmia Assay) initiative’s new paradigm.(6) This organization, regrouping researchers, medical agencies, and nonprofit institutions from all over the world (USA, Europe, Japan, Canada, etc.), and focusing on setting optimized rules to test new molecules’ potential cardiotoxicity, recently suggested to include in vitro assays in hiPS-derived cardiomyocytes.(7) But—and unfortunately there is a but—most of these iPS-derived cells present immature characteristics, resembling more fetal than adult differentiated cells, calling for optimized protocols and techniques.
In addition to these limitations, it is fascinating to think that we still don’t entirely understand reprogramming. For example, we can dissect the process in successive steps and we can validate the pluripotency of the reprogrammed cells many different ways, but we still don’t know exactly how it works, how four factors can induce such a drastic change of fate. With these questions, and some others still unsolved (the risk of tumorigenicity is a real obstacle), major breakthroughs most likely still lie ahead of us with iPS technology.
Amélie Rezza is innovation project manager at genOway, and specializing in advanced biotechnologies.