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

7.项目总结 申请者Asymmetrex是一家融资前的生物技术初创公司。Asymmetrex正在申请一项 小型企业创新研究第一阶段拨款，以达致技术基准，以加强其 一项新技术的商业开发，以满足干细胞研究中尚未得到满足的主要需求 干细胞医学。目前，还没有一种方法可以提供对围产儿的具体和准确的计数 或出生后组织干细胞。组织干细胞的分子生物标记物缺乏足够的特异性来计数 不包括承诺的祖细胞，这些祖细胞的数量比组织干细胞多几个数量级 震级。估计组织干细胞数量的最好、最受推崇的方法是 极限稀释法检测NOD/SCID小鼠再生细胞(LDSRC)。然而，LDSRC检测已经 有几个缺点。这是昂贵的和劳动密集型的，需要许多动物和几个月的时间来 它将干细胞植入的差异与干细胞数量的差异混为一谈；而且它只是 对造血干细胞(HSCs)有效。Asymmetrex开发了一种新的专利技术，名为 AlphaSTEM检测™能够特异性地计数来自许多不同围产期和 出生后组织，包括具有临床意义的组织，如骨髓、脐带血、肝脏和 间充质组织。AlphaSTEM测试™使用计算模拟来提取干细胞- 来自连续传代培养的简单细胞计数数据的特定计数和细胞动力学因子。这个 AlphaSTEM测试™的基本原理是对经历不对称自我检测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专有属性。AlphaSTEM 测试™也可用于检测候选药物对组织干细胞的影响。此功能提供了一个 新的创新药物评价方法，特别是用于干细胞毒性药物的早期检测。这类药物 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已经对阿尔法干细胞测试™进行了初步验证，用于细胞治疗和药物 开发应用，分别与已公布的LDSRC数据进行比较，并对几个 众所周知的毒品。尽管是积极的，但到目前为止，这些早期的验证被证明不足以获得 商业成功所需的行业和市场买入水平。Asymmetrex将聘用经过良好审查的 专家签约研究机构将与AlphaSTEM测试™HSC进行正面比较 将结果计数到LDSRC HSC估计结果；并评估足够的候选药物以估计 AlphaSTEM试验™用于识别可能失败的候选药物的阳性预测值 后来由于导致慢性器官衰竭而进行了昂贵的临床试验。这项研究的成功将会增加 业界和市场相信，AlphaSTEM测试™实际上是特定情况下长期需要的方法 用于研究和医学的围产期和出生后组织干细胞的准确定量。

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.