Methods to Improve Reproducibility of Human iPSC Derivation, Growth and Differentiation (SBIR) (R44 Clinical Trial Not Allowed)

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Human induced pluripotent stem cells (iPSCs) have been used with great success to mimic the differentiation of a variety of tissues, understand early development and study human diseases. Despite approaches that have made the derivation, growth and differentiation of iPSCs more efficient, there remains significant variability in reprogramming efficacy, genomic integrity and developmental potential of iPSCs derived from a single fibroblast or tissue sample. Thus, iPSCs derived from the same sample may differ in their in vitro growth characteristics and their ability to re-differentiate into the desired tissue type. A variety of issues may affect derivation of the iPSCs and their growth, stability and differentiation, including the specific characteristics of the starting cell or tissue sample (e.g., age of donor, tissue type and anatomical location, physiological and disease state), the methods and protocols used to induce pluripotency (e.g., transcription factors, small molecules, cell fusion), the choice of growth factors and other culture conditions, method of storage of cell lines, etc. Further challenges include growing and maintaining sufficient quantities of iPSC lines in culture without changes in their properties, as well as the ability of multiple investigators to identify and authenticate iPSC lines as part of their research. This Funding Opportunity Announcement (FOA) will support SBIR projects to develop novel, reliable and cost-effective methods to standardize and increase the utility and reproducibility of iPSCs at all stages, from their derivation to their research and clinical applications.

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