Imanis Life Sciences, LLC — Department of Health and Human Services SBIR Phase I: 200

Description

DESCRIPTION provided by applicant Induced pluripotent stem cells iPSC derived from somatic cells can be differentiated into various cell lineages They are valuable tools in basic cell and developmental biology research and as a potential source of regenerative cells for clinical applications However numerous challenges remain in the field of iPSC research including the need for methods that allow longitudinal noninvasive in vivo monitoring of transplanted cells in multiple animal species and in humans The reporter gene used for this type of cell marking should encode a protein that is non immunogenic can be monitored by noninvasive imaging using clinically approved radiotracers that are readily available can be used in small and large animal models and does not interfere with cellular function NIS the thyroidal sodium iodide symporter is an ideal reporter gene for cell tracking applications NIS is endogenously expressed in thyroid follicular cells where its role is to concentrate iodine for the synthesis of thyroid hormones For more than years thyroidal NIS expression has been clinically exploited providing the basis for I gamma camera or SPECT CT imaging in thyroid disorders and for I tumor ablation of metastatic thyroid cancer Imanis Life Sciences was founded in to accelerate research in regenerative medicine by providing a comprehensive set of reagents and imaging services to facilitate NIS reporter gene labeling and noninvasive monitoring of cellular therapies The overall goal of this grant is to develop NIS expressing stem cells and iPSC whose differentiated progeny can be serially imaged noninvasively in small and large animal models During the Phase I period we will introduce the NIS gene into either of two genomic safe harbors AAVS and ROSA of a human iPSC line with NIS gene expression controlled by EF a or CAG promoters The iPSC will be differentiated into cells of the three germ layers cardiomyocytes mesoderm insulin producing beta cells endoderm and neuronal cells ectoderm and NIS expression will be monitored We hypothesize that NIS gene expression will be constitutively expressed and will not be silenced in undifferentiated or differentiated progeny regardless of lineage thus enabling long term monitoring of the gene marked cells in vivo PUBLIC HEALTH RELEVANCE Stem cells capable of differentiating into various tissues for repair and regeneration are being developed in animal models but it is difficult to monitor the fate of these therapeutic cells We thus need a reliable and quantitative method that allows cell fate monitoring in small and large animal models In this grant we will develop the NIS imaging technology as a solution for cell fate monitoring with the goal of accelerating research and development of these therapies into the clinic Reagents generated here will also be a valuable resource for the research community in general