SBIR Phase I: Novel partial cellular reprogramming method for the production of ex vivo blood

SBIR 第一阶段：用于生产离体血液的新型部分细胞重编程方法

• 批准号: 1315876
• 负责人: Cristopher Geiler
• 金额: $ 14.95万
• 依托单位: Advanced Life Technologies
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-01 至 2013-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1315876&HistoricalAwards=false
• 关键词: SBIR; Phase; Novel; partial; cellular

This Small Business Innovation Research (SBIR) Phase I project will develop advanced methods to temporarily reprogram hematopoietic stem cells (HSCs) that will enable ex vivo production of blood in quantities suitable for transfusion. A transfection-free method will be used that can be easily translated into clinical use. Every two seconds someone in the U.S. needs blood and more than 38,000 blood donations are needed every day. In order for ex vivo blood production to be clinically relevant, the expansion cell culture must be able to produce red blood cells in the range contained in a unit of blood: 2.5x1012cells. There exists a fundamental obstacle in reaching this number of cells. CD34+(HSCs) and erythroid progenitors are typically only capable of short-term, or restricted ex vivo expansion. The main objective of this project is to reprogram CD34+(HSCs) such that cellular mechanisms are activated to force cellular proliferation. Despite research efforts from around the world, reaching clinical significant quantities of blood in culture has not been previously possible. The goal is to produce clinically relevant quantities of blood and create a shift in clinical practice paradigms for the treatment of the anemic patient as well as the blood banking industry.What are the broader impacts of the proposed activity?The broader impact/commercial potential of this project, if successful, will be to create a viable alternative to allogenic blood transfusion, and compete with traditional blood banking and the use of recombinant erythropoietin (EPO). We expect that successful development of this technique will have a high societal impact on safety and availability of blood for transfusions as well as a reduction in hemolytic transfusion reactions. Although the safety of transfusions has improved markedly there is still a non-zero probability of getting HIV (1:1.8 Million), or Hepatitis C (1:1 Million). This work is expected to significantly enhance the scientific and technological understanding of ex vivo production of blood and provide a pathway to translation into clinical medicine. This project will have a significant impact in the $20 billion global blood transfusion market, as well as the EPO market, which is valued at about $53 Billion.

这个小型企业创新研究（SBIR）第一阶段项目将开发先进的方法来暂时重新编程造血干细胞（HSC），这将使体外生产的血液数量适合输血。 将使用一种无转染的方法，可以很容易地转化为临床使用。在美国，每两秒钟就有一个人需要输血，每天需要献血的人数超过38,000人。为了使离体血液生产具有临床相关性，扩增细胞培养物必须能够产生单位血液中所含范围内的红细胞：2.5x1012个细胞。在达到这个数量的细胞方面存在着一个根本性的障碍。 CD 34+（HSC）和红系祖细胞通常仅能够进行短期或受限的离体扩增。 该项目的主要目标是重新编程CD 34+（HSC），从而激活细胞机制以迫使细胞增殖。 尽管来自世界各地的研究努力，达到临床显着数量的血液在文化以前是不可能的。目标是生产临床相关数量的血液，并为贫血患者的治疗以及血库行业的临床实践模式创造转变。拟议活动的更广泛影响是什么？该项目的更广泛的影响/商业潜力，如果成功的话，将是创造一个可行的替代异体输血，并与传统的血库和重组促红细胞生成素（EPO）的使用竞争。我们预计，这项技术的成功开发将对输血的安全性和可用性以及溶血性输血反应的减少产生很大的社会影响。尽管输血的安全性有了显著改善，但感染艾滋病毒（1：180万）或丙型肝炎（1：1万）的概率仍然不是零。 这项工作预计将显着提高科学和技术的理解离体生产的血液，并提供一个途径，转化为临床医学。该项目将对价值200亿美元的全球输血市场以及价值约530亿美元的EPO市场产生重大影响。