Increased Validation of a First Method for Counting Tissue Stem Cells Specifically

7. Project Summary The applicant, Asymmetrex, is a pre-finance biotechnology start-up company. Asymmetrex is applying for a Small Business Innovation Research Phase I grant to achieve technical benchmarks that will enhance its commercial development of a new technology that addresses a major unmet need in stem cell research and stem cell medicine. Currently, there are no methods that provide a specific and accurate count of perinatal or postnatal tissue stem cells. Molecular biomarkers for tissue stem cells lack sufficient specificity to count them without also counting committed progenitor cells that outnumber tissue stem cells by several orders of magnitude. The best available, and most well-regarded, method for estimating tissue stem cell number is the limiting dilution NOD/SCID mouse repopulation cell (LDSRC) assay. However, the LDSRC assay has several shortcomings. It is expensive and labor-intensive, requiring many animals and several months to perform; it conflates differences in stem cell engraftment with differences in stem cell number; and it only works for hematopoietic stem cells (HSCs). Asymmetrex has developed a new, patented technology called the AlphaSTEM Test™ that is able to specifically count tissue stem cells from many different perinatal and postnatal tissues, including clinically significant tissues like bone marrow, cord blood, liver, and mesenchymal tissues. The AlphaSTEM Test™ employs computational simulation to extract stem cell- specific counts and cell kinetics factors from simple cell count data from serially passaged cultures. The basic principle for the AlphaSTEM Test™ is mathematical detection of cells undergoing asymmetric self- renewal, which is an exclusive property of perinatal and postnatal tissue stem cells. The AlphaSTEM Test™ can also be used to detect drug candidate effects on tissue stem cells. This capability provides a new innovative drug evaluation assay, in particular for early detection of stem cell-toxic drugs. Such drugs cause chronic organ failure, which is a major cause of drug failure in expensive late clinical trials. Asymmetrex has performed initial validations of the AlphaSTEM Test™ for cell therapy and drug development applications by, respectively, comparison to published LDSRC data and evaluation of several well-known drugs. Though positive, so far, these early validations have not proved adequate to gain the level of industry and market buy-in needed for commercial success. Asymmetrex will employ well-vetted, expert contract research organizations to make a head-to-head comparison of AlphaSTEM Test™ HSC count results to LDSRC HSC estimation results; and evaluate sufficient drug candidates to estimate the positive predictive value (PPV) of the AlphaSTEM Test™ for identifying drug candidates that are likely to fail later in expensive clinical trials due to inducing chronic organ failure. Success in this research will increase industry and market confidence that the AlphaSTEM Test™ is, in fact, the long-needed method for specific and accurate quantification of perinatal and postnatal tissue stem cells for research and medicine.8. Project Narrative Many areas of human health will benefit from a method to count perinatal and postnatal tissue stem cells specifically and accurately for the first time. Areas of application are stem cell research, cancer cell research, stem cell transplantation medicine, environmental health science, and drug development.