HTS/CryoStor-Liver- Is Viability Linked to Function?

HTS/CryoStor-肝脏 - 活力与功能相关吗？

• 批准号: 6740529
• 负责人: Robert G Van Buskirk
• 金额: $ 13.93万
• 依托单位: CELL PRESERVATION SERVICES, INC.
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-08-15 至 2005-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6740529
• 关键词: apoptosis; bioinformatics; cell component structure /function; cell population study; cryopreservation; cytotoxicity; enzyme linked immunosorbent assay; high performance liquid chromatography; liver cells; proteomics; technology /technique development; western blottings

DESCRIPTION (provided by applicant): BioLife Solutions Inc is a Biological Packaging company dedicated to developing improved solutions for hypothermic storage (4 to 8C) and cryopreservation (-196C) of human cells and tissues. The HTS platform consists of HTS-BASE, HTS-DCC, HTS-FRS and custom hypothermic preservation solutions currently being designed for clients in the Regenerative Medicine market. BioLife's CryoStor cryopreservation solution platform is designed for storage of cells and tissues in liquid nitrogen. BioLife's solutions are designed by f_ understanding the molecular details of cell death cascades that can be activated as a consequence of hypothermic storage or cryopreservation. Once understood, solution formulation is altered such that these cell death processes are inhibited. As a consequence of this rational, molecular approach, BioLife's HTSFRS is superior to LIW Solution (ViaSpan), the solution currently used for hypothermic preservation of most human organs for transplantation. Similarly, BioLife's serum-free CryoStor series may be better for cryopreservation than the current ATCC industry protocol. BioLife's solutions are now FDA-approved as part of BioHea_'s IND in cellular cardiomyoplasty. This success captured the interest of Tissue Transformation Technologies (T3), which plans cell therapy applications with primary human hepatocytes to treat liver disease. BioLife developed a prototype HTS-LIVER platform that preserves the viability of a human hepatoma cell line several-fold longer than UW. The development of CryoStor-BASE suggests that the development of a CryoStor-LIVER platform is also probable. The Specific Aims of this proposal are to determine if: (1) HTS-LIVER works equally as well with primary human hepatocytes as it does with a human hepatoma cell line; (2) viability and function of hypothermically preserved primary human hepatocytes are linked; (3) the same modifications to HTS-BASE that generated HTS-LIVER can result in the development of CryoStor-LIVER; (4) modifications to HTS-LIVER or CryoStor-LIVER can improve their abilities to protect cell viability and function during preservation. Development of HTS-LIVER and CryoStor-LIVER are critical to support T3's human hepatocyte cell therapy applications in Regenerative Medicine. In addition, development of improved hypothermic and cryogenic preservation platforms will immediately benefit T3 by providing a means to reach larger national and international research markets with primary human hepatocytes.

描述（由申请人提供）：BioLife Solutions Inc是一家生物包装公司，致力于开发用于人体细胞和组织低温储存（4至8 ℃）和冷冻保存（-196 ℃）的改进解决方案。HTS平台包括HTS-BASE、HTS-DCC、HTS-FRS和定制低温保存解决方案，目前正在为再生医学市场的客户设计。BioLife的CryoLife冷冻保存解决方案平台设计用于在液氮中储存细胞和组织。BioLife的解决方案是通过理解细胞死亡级联的分子细节而设计的，这些细胞死亡级联可以作为低温储存或冷冻保存的结果而被激活。一旦理解，溶液配方被改变，使得这些细胞死亡过程被抑制。由于这种合理的分子方法，BioLife的HTSFRS上级LIW溶液（ViaSpan），LIW溶液目前用于大多数人体器官移植的低温保存。同样，BioLife的无血清冷冻系列可能比当前ATCC行业方案更适合冷冻保存。BioLife的解决方案现已获得FDA批准，作为BioHea_细胞心肌成形术IND的一部分。这一成功引起了组织转化技术公司（T3）的兴趣，该公司计划用原代人肝细胞进行细胞治疗应用，以治疗肝脏疾病。BioLife开发了一个原型HTS-LIVER平台，该平台保留了比UW长几倍的人类肝癌细胞系的活力。CryoStor-BASE的开发表明，CryoStor-LIVER平台的开发也是可能的。本提案的具体目的是确定：（1）HTS-LIVER与原代人肝细胞的作用是否与其与人肝癌细胞系的作用相同;（2）低温保存的原代人肝细胞的活力和功能是否相关;（3）对HTS-BASE进行的与生成HTS-LIVER相同的修饰是否可导致CryoStor-LIVER的开发;（4）对HTS-LIVER或CryoStor-LIVER的修饰可以提高它们在保存期间保护细胞活力和功能的能力。HTS-LIVER和CryoStor-LIVER的开发对于支持T3在再生医学中的人类肝细胞治疗应用至关重要。此外，改进的低温和低温保存平台的开发将通过提供一种利用原代人肝细胞进入更大的国内和国际研究市场的手段，立即使T3受益。