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

7.项目摘要 申请人Asymmetrex是一家生物技术初创公司，尚未获得融资。Asymmetrex正在申请 小企业创新研究第一阶段赠款，以实现技术基准，将提高其 一项新技术的商业开发，解决了干细胞研究中未满足的主要需求， 干细胞医学目前，还没有方法提供具体和准确的围产期计数， 或者是出生后的组织干细胞。组织干细胞的分子生物标志物缺乏足够的特异性来计数 他们没有计算定向祖细胞，其数量超过组织干细胞几个数量级。 大小估计组织干细胞数量的最佳方法是 有限稀释NOD/SCID小鼠再增殖细胞（LDSRC）测定。然而，LDSRC测定具有 几个缺点。这是昂贵和劳动密集型，需要许多动物和几个月， 它将干细胞植入的差异与干细胞数量的差异混为一谈;它只 对造血干细胞（HSC）有效。Asymmetrex开发了一种新的专利技术， AlphaSTEM Test™能够特异性计数来自许多不同围产期的组织干细胞， 出生后组织，包括临床上重要的组织，如骨髓、脐带血、肝脏，以及 间充质组织AlphaSTEM Test™采用计算机模拟来提取干细胞- 从连续传代培养物的简单细胞计数数据得到的特定计数和细胞动力学因子。的 AlphaSTEM Test™的基本原理是对经历不对称自显影的细胞进行数学检测。 更新，这是围产期和出生后组织干细胞的独有特性。AlphaSTEM Test™也可用于检测候选药物对组织干细胞的影响。此功能提供了 新的创新药物评估分析，特别是用于干细胞毒性药物的早期检测。此类药物 导致慢性器官衰竭，这是昂贵的后期临床试验中药物失败的主要原因。 Asymmetrex已经对AlphaSTEM Test™进行了初步验证，用于细胞治疗和药物治疗。 开发应用程序，分别与已公布的LDSRC数据进行比较，并评估几个 众所周知的毒品虽然积极的，但到目前为止，这些早期的验证还不足以获得 商业成功所需的行业和市场认可水平。阿斯美曲斯会聘请经过严格审查的 专家合同研究组织，对AlphaSTEM Test™ HSC进行头对头比较 将结果计数为LDSRC HSC估计结果;并评估足够的候选药物以估计 AlphaSTEM Test™的阳性预测值（PPV），用于识别可能失败的候选药物 后来在昂贵的临床试验中，由于诱导慢性器官衰竭。这项研究的成功将增加 行业和市场的信心，AlphaSTEM测试™是，事实上，长期需要的方法，为特定的 以及对围产期和出生后组织干细胞进行精确定量，用于研究和医学。

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.