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

增强对组织干细胞特异性计数方法的验证

• 批准号: 10080303
• 负责人: JAMES L SHERLEY
• 金额: $ 42万
• 依托单位: ASYMMETREX, LLC
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-23 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10080303
• 关键词: Acute; Address; Adoption; Animals; Area; Benchmarking; Biological; Biological Assay; Biological Markers; Biotechnology; Blood specimen; Bone Marrow; CD34 gene; Cell Count; Cell Culture Techniques; Cell Cycle Kinetics; Cell Fraction; Cell Therapy; Cells; Cellular Assay; Chronic; Clinical Trials; Collaborations; Computer Simulation; Data; Detection; Development; Drug Evaluation; Drug Industry; Early Diagnosis; Engraftment; Environmental Health; Evaluation; Excision; Failure; Grant; Health; Hematopoietic stem cells; Human; Industry; Kinetics; Legal patent; Literature; Liver; Mathematics; Medical; Medicine; Membrane Proteins; Mesenchymal; Methods; Misinformation; NOD/SCID mouse; Organ failure; Perinatal; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Phase II Clinical Trials; Phase III Clinical Trials; Predictive Value; Production; Property; Publishing; Reporting; Research; Research Contracts; Research Proposals; Serial Passage; Small Business Innovation Research Grant; Specificity; Stem Cell Research; Stem cell transplant; Technology; Test Result; Testing; Therapeutic; Time; Tissues; Toxic effect; Umbilical Cord Blood; Validation; Work; base; bone cell; cancer cell; clinically significant; drug candidate; drug development; drug testing; head-to-head comparison; innovation; molecular marker; new technology; postnatal; process optimization; self-renewal; stem cell population; stem cell therapy; stem cells; success; therapy development; tissue preparation; tissue stem cells; tool; transplantation medicine

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.

七、项目概要 申请人Asymmetrex是一家预融资生物技术初创公司Asymmetrex正在申请。 小型企业创新研究第一阶段拨款，用于实现技术基准，从而增强其 一项新技术的商业开发，解决干细胞研究中未满足的主要需求 目前，还没有方法可以提供特定且准确的围产期细胞计数。 或出生后组织干细胞的分子生物标志物缺乏足够的特异性来计数。 他们没有同时计算定型祖细胞，其数量比组织干细胞高出几个数量级 估计组织干细胞数量的最佳可用且最受好评的方法是。 有限稀释 NOD/SCID 小鼠再增殖细胞 (LDSRC) 测定 然而，LDSRC 测定有。 它有几个缺点，即成本昂贵且劳动强度大，需要许多动物和几个月的时间才能完成。 执行；它将干细胞植入的差异与干细胞数量的差异混为一谈； Asymmetrex 开发了一种名为造血干细胞 (HSC) 的新型专利技术。 AlphaSTEM Test™ 能够对来自许多不同围产期和不同阶段的组织干细胞进行特异性计数 产后组织，包括具有临床意义的组织，如骨髓、脐带血、肝脏和 AlphaSTEM Test™ 采用计算模拟来提取干细胞- 来自连续传代培养物的简单细胞计数数据的特定计数和细胞动力学因素。 AlphaSTEM Test™ 的基本原理是对经历不对称自噬的细胞进行数学检测。 更新，这是围产期和产后组织干细胞的专有特性。 Test™ 还可用于检测候选药物对组织干细胞的影响。 新的创新药物评价试验，特别是用于早期检测干细胞毒性药物此类药物。 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 已对细胞疗法和药物的 AlphaSTEM Test™ 进行了初步验证 开发应用程序分别通过与已发布的 LDSRC 数据进行比较并评估几个 尽管是众所周知的药物，但到目前为止，这些早期验证还不足以获得批准。 Asymmetrex 将采用经过严格审查的、商业成功所需的行业和市场支持水平。 专家合同研究组织对 AlphaSTEM Test™ HSC 进行面对面比较 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 Test™ 的阳性预测值 (PPV)，用于识别可能失败的候选药物 稍后在昂贵的临床试验中由于诱发慢性器官衰竭，这项研究的成功率将会增加。 行业和市场相信 AlphaSTEM Test™ 实际上是特定领域长期需要的方法 以及用于研究和医学的围产期和产后组织干细胞的准确定量。