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和其他定制保存解决方案，目前正在为再生医学市场的客户设计。BioLife的CryoGlycoprotein冷冻保存溶液平台设计用于在不含血清和DMSO水平降低的情况下将细胞和组织储存在液氮中。BioLife的解决方案是通过首先了解细胞死亡级联的分子细节来设计的，这些细胞死亡级联可能由于低温储存或冷冻保存而过早启动。一旦已知，溶液配方以抑制这些细胞死亡过程的方式改变。BioLife的HTS-FRS上级于UW解决方案（ViaSpan）-目前用于大多数人体器官储存的解决方案。同样地，BioLife的CryoTherapy系列在冷冻保存方面可能比当前的ATCC行业协议更好。BioLife的解决方案现在是BioHeart的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期提案致力于改进人体血管的低温和冷冻保存。生物生命公司与冷冻生命公司合作，保存的同种异体血管假体的主要供应商，因此可以开发改进的保存溶液，（1）不需要目前包含血清和硫酸软骨素，（2）利用BioLife最近关于细胞凋亡在保存失败中的作用的研究，从而改善保存的同种异体血管移植的结果。本提案的具体目的包括以下内容：（1）确定相对于ViaSpan，储存在HTS和冷冻液中的细胞活力的改善是否反映为功能的类似改善;（2）测试包含的其他调节细胞凋亡的药物改善HTS和冷冻液功效的潜在能力;（3）确定应用Ciphergen蛋白质芯片系统是否可以用于HTS和冷冻变体的高通量评估和/或确定保存的血管是否被细菌肠毒素污染，以及（4）测试可能赋予细胞不寻常的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.