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，致力于开发用于人体细胞和组织的低温（4至8 ℃）和冷冻保存（-196 ℃）的改进解决方案。该公司通过直接销售其两个平台解决方案HypoThermosol（HTS）和CryoThermosol以及与细胞治疗和组织工程公司执行定制解决方案优化计划合同来获得收入。HTS平台由HTS-BASE（原始HTS制剂）、HTS-DCC（一种控制阳离子通量的制剂）、HTS-FRS（一种控制自由基蓄积的制剂）和HTS-LIVER（一种控制肝细胞凋亡的制剂）组成。前三种HTS配方可通过MediaTech Inc获得，而第四种目前正在开发中。CryoGlycol是一种HTS溶液，设计用于改善冷冻保存，需要减少冷冻保护剂（例如DMSO）的量。BioLife还推出了一项包装和Downloading Diagnostics计划，该计划将允许目前使用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，冲击和压力变化的历史。BioLife的HTS平台解决方案最初设计用于保护基质附着细胞。但是，最近在BioHeart Inc成功的欧洲细胞心肌成形术试验中使用的悬浮人成肌细胞的HTS-FRS保存的临床成功，加上CryoLife在冷冻保存ATCC人杂交瘤方面的明显优势，最近由ATCC人员进行的实验，要求BioLife启动一项新的研究计划，以了解在保存前悬浮细胞发生的应力机制。提出了以下四个具体目标：SAI：通过占据整合素受体来改善保存，整合素受体反过来可以阻断失巢凋亡; SA 2：通过抑制由于悬浮过程发生的细胞形状变化来改善保存; SA 3：通过阻断FAS活化来改善保存，FAS活化是一种已知的死亡受体，公司将其与保存功效联系起来; SA 4：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。 这个第一阶段SBIR项目的目的是更好地了解需要控制的应力机制，以改善悬浮细胞的保存，这将导致HTS-SUSP的第二阶段开发。

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.