HTS-TEETH-A new preservation solution for avulsed teeth

描述（由申请人提供）：Cell Preservation Services Inc（CPSI）开发用于人体细胞和组织低温储存（40至80 ℃）和冷冻保存（-196 ℃）的生物包装新技术。HypoThermosol（HTS）平台包括HTS-PURGE、HTS-BASE、HTS-DCC、HTS-FRS、HTS-AIE和Gelatron以及再生医学市场客户使用的其他定制解决方案。该公司的无血清CryoGlycoprotein冷冻保存解决方案平台是专为细胞和组织储存在液氮中，并需要降低DMSO水平。CPSI的解决方案是围绕细胞死亡级联反应的分子事件而设计的，这些事件可以由于延长的保存储存而启动。一旦已知，溶液配方以抑制这些细胞死亡过程的方式改变。几种HTS变体已被证明比目前的商业解决方案（例如Viaspan）具有明显的优势。HTS和CryoTherapy溶液现在是FDA批准的几种细胞治疗IND的组成部分。再生医学的这一成功现在提供了临床应用机会，这是CPSI在其商业计划中最初没有设想的。CPSI发现，目前市面上唯一一种可用于短期保存撕脱牙齿的解决方案是Save-A-Tooth，这是Hanks平衡盐溶液（HBSS）的品牌名称。HBSS从未被设计为有效的低温储存溶液，CPSI将其用作阴性对照。鉴于HTS在室温下的稳定性以及CPSI使用其多溶液和竞争性应力途径假设开发细胞匹配保存溶液的能力，CPSI已决定开发一种HTS变体HTS-TEETH，该变体将专门用于撕脱牙齿的短期储存。五个具体目的（SA）如下：SA 1-测试当前HTS变体对牙周膜（PDL）细胞的保存作用，作为HTS-TEETH的候选基础溶液;分析细胞质凋亡途径（SA 2）以及由于PDL细胞的冷藏而激活的基因组应激和凋亡途径（SA 3）; SA 4-用基于来自SA 2，3的数据鉴定的调节剂修饰SA 1 HTS变体; SA 5-比较在SA 1-SA 4中开发的HTS-TEETH作为从NIH采购的PDL干细胞的保存溶液。第二阶段将致力于进行更全面的cDNA微阵列工作，分析细胞功能并在体内测试HTS-TEETH。

DESCRIPTION (provided by applicant): Cell Preservation Services Inc (CPSI) develops new technologies in Biological Packaging for hypothermic storage (40 to 80 C) and cryopreservation (-196C) of human cells and tissues. The HypoThermosol (HTS) platform consists of HTS-PURGE, HTS-BASE, HTS-DCC, HTS-FRS, HTS-AIE and GelStor as well as other custom solutions being utilized by clients in the Regenerative Medicine market. The Company's serum-free CryoStor cryopreservation solution platform is designed for cell and tissue storage in liquid nitrogen and requires reduced DMSO levels. CPSI's solutions are designed around the molecular events underlying cell death cascades that can be launched due to extended preservation storage. Once known, solution formulation is altered in such a manner that inhibits these cell death processes. Several HTS variants have been shown to have a marked benefit over present commercial solutions (e.g.Viaspan). HTS and CryoStor solutions are now components of several FDA-approved INDs in cell therapy. This success in Regenerative Medicine has now provided clinical application opportunities that were not originally envisioned by CPSI in its business plan. CPSI has discovered that the only solution commercially available for the short-term storage of avulsed teeth is Save-A-Tooth, a brand name for Hanks Balanced Salt Solution (HBSS). HBSS was never designed to be an effective hypothermic storage solution and is used by CPSI as its negative control. Given HTS's stability at room temperature and the ability of CPSI to develop cell-matched preservation solutions using its Multisolution and Competitive Stress Pathway hypotheses, CPSI has decided to develop an HTS variant, HTS-TEETH, that will be expressly developed for the short term storage of avulsed teeth. The five Specific Aims (SA) are the following: SA1-Test current HTS variants on the preservation of periodontal ligament (PDL) cells as candidate base solutions for HTS-TEETH; Analyze the cytoplasmic apoptosis pathways (SA2) and genomic stress and apoptosis pathways (SA3) activated as a consequence of chill storage of PDL cells; SA4-Modify the SA1 HTS variant with modulators identified based on data from SA2,3; SA5- Compare HTS-TEETH developed in SA1-SA4 as a preservation solution for PDL stem cells procured from NIH. Phase 2 will be dedicated to performing more comprehensive cDNA microarray work, analyzing cell function and testing HTS-TEETH in vivo.