Cellular Technologies

From Patients to Neurons and Back Again

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  Lee Rubin, PhD

  Professor; Director of Translational Medicine
  Dept of Stem Cell and Regenerative Biology, Harvard University; Harvard Stem Cell Institute

The foundational idea for the use of patient-specific induced pluripotent stem cells (iPSCs) in disease modeling was that this approach would result in a significant improvement in the efficiency of drug discovery and, eventually, in more success in the clinic. Whether this is true depends heavily on the predictive power of this human cell-centric approach, compared to that using cell lines of the types more widely employed in industry. This is a reasonable time to assess the amount of progress that has been made thus far.

Most of the work in my laboratory has focused on studying neurodegenerative and neuropsychiatric diseases using human neurons and other cells derived from iPSCs. Our work, as well as that from numerous other labs, has shown that some, but not all, aspects of these disorders can be reproduced in rather simple tissue culture environments. Moreover, recent studies have demonstrated that iPSC-based research can provide new information concerning previously unrecognized disease features, as well as generate data supporting the use of specific therapeutics on defined patient populations. On the other hand, it seems increasingly likely that more complex in vitro systems, particularly those in which neurons differentiate in 3-dimensional conditions, will be required to model other disease-associated features. These include changes that either require significant amounts of time to occur or are associated with modified neural circuit behavior. I will present several examples of work showing the advantages and limitations of iPSC-derived neuronal work.