High throughput Electrophysiological Purification Array (HEPA) for cell based therapies Abstract: Patient-specific reprogrammed somatic cells (induced pluripotent stem cells or iPSCs) have raised hope for revolutionary regenerative treatments for heart, lung and blood diseases and drug development applications. For example, these iPS cells can be differentiated into cardiomyocytes and have the capability to regenerate and undergo extensive repair after myocardial infarction. However, the differentiation efficiency is low and differentiated cardiomyocytes are heterogeneous, containing mainly ventricular cardiomyocytes with varying maturation states. Since these iPSCs differentiate in vitro into a mixture of different lineages, purification of the differentiated cells, as well as their separatio from tumor-forming progenitors, is essential. But establishment of effective separation methods to isolate differentiated cells and exclude cells that lead to teratoma formation is the major challenge in translating advances in stem cell biology into tissue replacement therapies. Conventional separation techniques, such as microscope-assisted manual isolation is time consuming whereas fluorescence-activated cell sorting, and magnetic-activated cell sorting, require intensive labor, exogenous labeling or genetic modification and, as such, are not readily adaptable to clinical applications. To address these issues, therefore, Biopico Systems teams with the University of California, Irvine to develop High throughput Electrophysiological Purification Array (HEPA) system for label-free cell sorting of induced pluripotent stem cells and their differentiated progeny based on their response to electrical stimulation. This Phase I effort will provide the foundation for deriving patient specific cells for potential clinical use in phaseII with a goal of obtaining 100% specificity at high viability, high throughput and a capacity to sort multiple cell phenotypes for therapeutic applications. In order to demonstrate the feasibility of the proposed platform, we will combine the technologies of flow- based field potential sensing in an electrode array with high speed signal processing and high throughput cell sorting to rapidly detect, identify, and sort millions of specific cells that will allow the successful translation of advances in stem cell biology into therapies for cardiac diseases.

Public Health Relevance

The development of a novel label free high-throughput iPSC sorting technology of Biopico systems will contribute to the goals of Directed Stem Cell Differentiation for Cell-Based Therapies in avoiding the potential serious side-effects of teratoma formation, aberrant reprogramming, and the presence of transgenes. Our endeavor to overcome the barriers that prevent successful translation of advances in stem cell biology into clinical therapy is highly significant for the improvement of human health and the control of human diseases. In particular, the system can be a potential tool for generating cells of required lineages and in the quantities for the replacement of lost progenies, remyelination, and support of adjacent cells at risk in cardiac disorders such as myocardial infarction as well as for studyin development and the progression of such diseases.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Small Business Innovation Research Grants (SBIR) - Phase I (R43)
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Special Emphasis Panel (ZRG1-IMST-K (14))
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Lee, Albert
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United States
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