Hypothermic and Cryopreservation of Human Blood Vessels

描述（由申请人提供）：BioLife Solutions Inc .是一家生物包装公司，致力于开发人类细胞和组织的低温储存（4至8摄氏度）和低温保存（-196摄氏度）的改进解决方案。HTS平台包括HTS- base、HTS- dcc、HTS- frs以及目前正在为再生医学市场客户设计的其他定制保存解决方案。BioLife的CryoStor冷冻保存溶液平台专为在无血清和DMSO水平降低的液氮中储存细胞和组织而设计。BioLife的解决方案是通过首先了解细胞死亡级联的分子细节而设计的，这种级联可能由于低温储存或低温保存而过早启动。一旦知道，溶液配方就会改变，从而抑制这些细胞死亡过程。BioLife的HTS-FRS优于UW溶液（ViaSpan）——目前用于大多数人体器官储存的溶液。同样，BioLife的CryoStor系列可能比目前的ATCC工业协议在低温保存方面更好。BioLife的解决方案现在是BioHeart获得fda批准的细胞心肌成形术IND的一部分，这是一个成功的心脏再生医学国际项目，部分原因是BioLife的HTS-FRS。该II期计划致力于改进人体血管的低温和低温保存。BioLife已经与crylife公司合作，crylife公司是保存同种异体移植血管假体的主要供应商，因此可以开发出改进的保存溶液，(1)不需要目前的血清和硫酸软骨素，(2)利用BioLife最近关于细胞凋亡在保存失败中的作用的研究，从而改善保存同种异体移植血管的移植结果。本提案的具体目标包括以下内容：(1)确定相对于ViaSpan， HTS和CryoStor溶液中细胞活力的提高是否反映在功能的类似改善上；(2)检测其他调节细胞凋亡的药物是否有可能提高HTS和CryoStor的疗效；(3)确定使用Ciphergen ProteinChip系统是否可以用于高通量评估HTS和CryoStor变体和/或确定保存的血管是否被细菌肠毒素污染；(4)测试可能赋予细胞异常低温恢复能力的自然因素。

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 other custom 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 without serum and with reduced levels of DMSO. BioLife's solutions are designed by first understanding the molecular details of cell death cascades that can be prematurely launched as a consequence of hypothermic storage or cryopreservation. Once known, solution formulation is altered in such a manner that inhibits these cell death processes. BioLife's HTS-FRS is superior to UW Solution (ViaSpan) - the solution currently being used for most human organ storage. Similarly, BioLife's CryoStor series may be better at cryopreservation than the current ATCC industry protocol. BioLife's solutions are now a part of BioHeart's FDA-approved IND in cellular cardiomyoplasty - a successful international program in cardiac Regenerative Medicine made possible, in part, by BioLife's HTS-FRS. This Phase II proposal is dedicated to the improved hypothermic and cryopreservation of human blood vessels. BioLife has teamed with CryoLife Inc., a major supplier of preserved, allograft vascular prostheses, so that improved preservation solutions can be developed that (1) do not necessitate the current inclusion of serum and chondroitin sulfate and (2) harness BioLife's recent research on the role of apoptosis in preservation failure so that outcome is improved in the transplant of preserved allograft vessels. The Specific Aims of this proposal include the following: (1) Determine if the improvement in viability of cells stored in HTS and CryoStor solutions relative to ViaSpan is mirrored by a similar improvement in function; (2) Test the inclusion of other agents that modulate apoptosis for their potential abilities to improve HTS and CryoStor efficacy; (3) Determine if applying the Ciphergen ProteinChip system can be used for either high throughput assessment of HTS and CryoStor variants and/or determining whether preserved vessels are contaminated with bacterial enterotoxins and (4) test for natural factors that may confer unusual hypothermic resilience in cells.