Post thaw assessment of umbilical cord blood

描述（由申请人提供）：项目概述。本研究的长期目标是开发解冻后评估方法，允许移植地点在移植前评估脐带血单位（UCB），并可被脐带血库用作其质量控制计划的一部分。UCB是用于治疗包括血癌在内的多种疾病的造血干细胞（hsc）的重要来源。目前，UCB占美国每年所有HSC移植手术的28%，迄今为止，全球已有14,000例人类移植手术。UCB的优点有很多：它可以在没有风险的情况下收集；银行的即时可用性；更广泛地获得各种HLA基因型，大约有35万单位；较低的免疫反应性和较低的固有病原体传播。所有迹象表明，UCB的临床应用将继续增长。绝大多数UCB单位被收集并冷冻保存以供以后使用。通过规范收集、处理和保存，为提高UCB单位的质量投入了相当大的努力。尽管在标准化UCB处理方面做出了上述努力，但仍有关于UCB单元解冻后恢复不良的报告。目前还没有一个标准的度量或测量来量化UCB产品解冻后的效力。移植研究表明，CD34+和集落形成单位（CFU）含量与移植和长期存活相关。这两种方法都是评估解冻后功能的候选方法。造血细胞产物表现出显著的细胞损失

DESCRIPTION (provided by applicant): Project Summary. The long term objective of this investigation is to develop methods of post-thaw assessment that permit transplant sites to assess umbilical cord blood units (UCB) prior to transplant and can be used by UCB banks as a part of their quality control program. UCB is an important source of hematopoietic stem cells (HSCs) used in the treatment of a variety of diseases including blood cancer. UCB now comprises 28% of all HSC transplants performed in the USA every year, with 14,000 transplants to date performed in humans worldwide. The advantages of UCB are numerous: it can be collected at no risk to the donor; immediate availability in a bank; wider availability of diverse HLA genotypes with approximately 350,000 units banked; lower immune reactivity and lower inherent pathogen transmission. All indications are that the clinical applications for UCB will continue to grow. The vast majority of UCB units are collected and cryopreserved for later use. Considerable effort has been invested to improve the quality of UCB units by standardizing collection, processing and preservation. In spite of the aforementioned efforts in standardizing UCB processing, there have been reports of poor post thaw recovery of UCB units. There is not yet a standard metric or measure by which to quantify post-thaw potency of UCB products. Transplant studies of UCB suggest that both CD34+ and colony forming unit (CFU) content correlate with engraftment and long- term survival. Both of these assays are candidates for assessing post-thaw function. Hematopoietic cell products exhibit significant cell losses resulting from post-thaw apoptosis. More recent studies demonstrated that cells expressing early signs of apoptosis did not engraft in an animal transplant model suggesting significant functional impairment of the cells. Therefore, characterizing post-thaw apoptosis may be a clinically relevant post-thaw quality metric for UCB. Post thaw apoptosis may also be a marker for aging of the cells during storage. It is our hypothesis that post-thaw apoptosis measures can be a clinically relevant metric for damage during the preservation process and storage of UCB units.