Post thaw assessment of umbilical cord blood

脐带血解冻后评估

• 批准号: 8261833
• 负责人: ALLISON HUBEL
• 金额: $ 11.4万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-04-15 至 2014-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8261833
• 关键词: Adult; Animals; Apoptosis; Biological Assay; Biological Preservation; CD34 gene; Cell Aging; Cell Count; Cells; Collection; Colony-Forming Units Assay; Colony-forming units; Cryopreservation; Development; Disease; Engraftment; Exhibits; Flow Cytometry; Freezing; Genotype; Hematopoietic; Hematopoietic Neoplasms; Hematopoietic stem cells; Human; Immune; Immunotherapy; Investigation; Kinetics; Life; Lymphocyte; Maps; Measures; Membrane; Mesenchymal Stem Cells; Methods; Metric; Modeling; Monitor; Mononuclear; National Heart, Lung, and Blood Institute; Outcome Study; Phase; Process; Quality Control; Recovery; Regenerative Medicine; Reporting; Risk; Site; Source; Staining method; Stains; Stem cell transplant; Temperature; Testing; Therapeutic Uses; Time; Transplantation; Umbilical Cord Blood; United States Food and Drug Administration; Variant; Whole Blood; annexin A5; biobank; caspase-3; cell age; clinical application; clinically relevant; experience; functional disability; improved; monocyte; pathogen; programs; standard measure; transmission process

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.

描述（由申请人提供）：项目摘要。本研究的长期目标是开发解冻后评估方法，允许移植部位在移植前评估脐带血单位（UCB），并可由UCB库用作其质量控制计划的一部分。脐血是造血干细胞（HSC）的重要来源，用于治疗包括血癌在内的多种疾病。UCB现在占美国每年进行的所有HSC移植的28%，迄今为止在全球范围内进行了14，000例移植。UCB的优点很多：它可以在对供体没有风险的情况下收集;在库中立即可用;具有大约350，000个单位的不同HLA基因型的更广泛可用性;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备后用。已投入相当大的努力，通过标准化收集、加工和保存来提高UCB单位的质量。尽管在标准化UCB处理方面做出了上述努力，但仍有报告称UCB单位的解冻后回收率较差。目前还没有一个标准的指标或措施来量化UCB产品的解冻后效价。脐带血的移植研究表明，CD 34+和集落形成单位（CFU）含量与植入和长期生存相关。这两种测定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， 解冻后的细胞凋亡最近的研究表明，表达细胞凋亡的早期迹象的细胞没有在动物移植模型中移植，表明细胞的显著功能损伤。因此，表征解冻后细胞凋亡可能是UCB的临床相关解冻后质量指标。解冻后细胞凋亡也可能是储存期间细胞老化的标志。这是我们的假设，解冻后的凋亡措施可以是一个临床相关的指标，在保存过程中的损害和存储的脐带血单位。