With more than 200 different cell types in the human body, a key goal of Cellular Dynamics International (CDI), a Fujifilm company, is to continue to expand the portfolio of available human iPSC-derived tissues where possible and where there is a scientific need. For example, CDI’s first-generation GABAergic iCell Neurons are inhibitory cortical neurons that recapitulate many features of human neurons. The utility of this cell type was immediately demonstrated as an alternative model to primary animal-based neuronal preparations for assessing neurite outgrowth as well as developmental and general neuronal cytotoxicity. However, as they are a primarily inhibitory neuronal population, they provided limited utility for assessing networked neuronal electrical activity.
Thus, the second generation of primarily excitatory glutamatergic iCell Glutaneurons were developed. These neurons, when coupled with MEA technology, allow researchers to evaluate networked neuronal electrical activity and spontaneous bursting in vitro, thereby providing a previously unattainable human neuronal model to test excitotoxicity and electrical (seizurogenic) activity. Like iCell Cardiomyocytes and iCell Cardiomyocytes2, iCell Glutaneurons have entered large-scale consortia work. Specifically, the NeuTox HESI initiative aimed at developing a predictive seizurogenic assay. The same success is expected for NeuTox with iPSC-derived neurons as has been observed in the cardiovascular field with iPSC-derived cardiomyocytes and the CiPA and CSAHi initiatives.
iPSC technology has made significant contributions to the biologists’ toolbox and will continue to advance the frontiers of science. Recently, Cynata Therapeutics (ASX:CYP) commenced the world’s first clinical trial involving an allogeneic iPSC-derived therapeutic product, which it derived from CDI’s iPSCs. Similarly, many researches are investigating methods to enhance the functionality of terminally differentiated cells types. Most of this discussion has focused on iPSC-derived cardiomyocytes, hepatocytes, and neurons. Enhanced functionally will likely result from multiple tactics including both pre-and post-differentiation strategies. Toward this goal, one school of thought supports the use of complex culture systems such as 3D culture techniques and co-culture strategies, with multiple cell types, to better recapitulate the in vivo microenvironment (e.g., organ-on-a-chip).
In the case of iPSC-derived cardiomyocytes, 3D culture and continuous pacing has been shown to enhance or provide missing functionality such as positive force-frequency relationship and enhance positive inotropic response (Zhang et al 2017, Feric et al., 2017, Ravenscroft, et al., 2016). In addition, iPSC-derived hepatocytes have shown superiority over many immortalized hepatocyte lines (Gao et al., 2017) and 3D culture strategies improve their functionality including increasing CYP activity (Hancock et al., 2017).
While one of the main characteristic of iPSC technology is the ability to study samples from different genetic backgrounds, the reality is that most commercially available iPSCs are from apparently healthy sources, many groups do not have access to patient samples or the infrastructure to manufacture at scale, or the resources to genetically engineer specific models. Thus, there is a significant need to make more iPSCs and iPSC-derived tissues to better represent healthy and diseased populations and to make these resources available to the larger research community.
Toward this goal, CDI is extending its portfolio to include an array of disease and diverse populations. One effort at CDI is to provide access to diverse populations for personalized toxicity testing or clinical trial “in a dish.” CDI is also committed to developing cell banks for the research community. Together, these efforts will continue to position CDI as a preferred partner for iPSC-based research across academia and industry.