Improved Preservation of Suspended Cells

描述(由申请人提供)： BioLife Solutions Inc.是一家生物包装公司，致力于为人类细胞和组织的低温(4至8摄氏度)和低温保存(-196摄氏度)开发改进的解决方案。该公司通过直接销售其两个平台解决方案HypoThermosol(HTS)和CryoStor以及执行与细胞治疗和组织工程公司的定制解决方案优化计划合同而获得收入。HTS平台由HTS-BASE(最初的HTS配方)、HTS-DCC(控制阳离子流量的配方)、HTS-FRS(控制自由基积累的配方)和HTS-Liver(控制肝细胞凋亡的配方)组成。前三个HTS配方可通过Mediatech Inc.获得，而第四个配方目前正在开发中。CryoStor是一种高温超导解决方案，旨在改善低温保存，从而减少低温保护剂(如DMSO)的用量。BioLife还推出了一项包装和可下载诊断程序，允许目前使用HTS的细胞治疗/组织工程公司跟踪细胞产品运输过程中发生的温度、休克和压力变化的历史。BioLife的HTS平台解决方案最初是为了保护衬底附着细胞而设计的。但是，生物心脏公司在欧洲成功的细胞性心肌成形术试验中使用HTS-FRS保存悬浮的人类成肌细胞最近在临床上取得了成功，再加上CryoStor在冷冻保存ATCC人类杂交瘤方面的明显优势，ATCC人员最近进行的实验要求BioLife启动一项新的研究计划，以了解在保存之前悬浮细胞所受到的压力机制。他们提出了四个具体目标如下：SAI：通过占据整合素受体进而阻断失巢凋亡来提高保存率；SA2：通过抑制悬浮过程中细胞形状的变化来提高保存率；SA3：通过阻断Fas的激活来提高保存率；SA4：测试双功能自由基抑制剂Emblica，以确定自由基/金属螯合剂的组合是否可以改善悬浮细胞的保存性。 这个第一阶段SBIR项目的目的是更好地了解需要控制的压力机制，以改善悬浮细胞的保存，这将导致HTS-SUSP第二阶段的开发。

DESCRIPTION (provided by applicant): BioLife Solutions Inc. is a Biological Packaging Company dedicated to developing improved solutions for hypothermic (4 to 8C) and cryopreservation (-196C) of human cells and tissues. The Company generates revenues from direct sales of its two platform solutions, HypoThermosol (HTS) and CryoStor as well as executing Custom Solution Optimization Program contracts with cell therapy and tissue engineering companies. The HTS platform consists of HTS-BASE (the original HTS formulation); HTS-DCC (a formulation that controls cation flux); HTS-FRS (a formulation that controls free radical accumulation) and HTS-LIVER (a formulation that controls apoptosis in hepatocytes). The first three HTS formulations are available through MediaTech Inc, whereas the fourth is currently under development. CryoStor is an HTS solution designed for improved cryopreservation necessitating reduced amounts of cryoprotective agent (e.g. DMSO). BioLife has also launched a program in Packaging and Downloadable Diagnostics that will allow cell therapy/tissue engineering companies who currently use HTS to track the history of temperature, shock, and pressure changes that occur during cell product transit. BioLife's HTS platform solutions were designed originally to protect substrate-attachment cells. But the recent clinical success of HTS-FRS preservation of suspended human myoblasts used in BioHeart Inc's successful European cellular cardiomyoplasty trials, coupled with CryoStor's apparent superiority in cryopreserving ATCC human hybridomas, experiments recently performed by ATCC personnel, has demanded that BioLife launch a new research program to understand the stress mechanisms that occur to suspended cells prior to preservation. Four Specific Aims are proposed as follows: SAI: Improving preservation by occupying integrin receptors that, in turn, could block anoikis; SA2: Improving preservation through inhibiting cell shape change that occurs due to the suspension process; SA3: Improving preservation by blocking FAS activation, a known death receptor that the Company has linked to preservation efficacy; SA4: Test the dual-function free radical inhibitor, Emblica, to determine if a combination free radical/metal chelator can improve the preservation of suspended cells. The intent of this Phase I SBIR project is to better understand the stress mechanisms that need to be controlled for improved preservation of suspended cells that will lead to the Phase II development of HTS-SUSP.