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(申请人提供)：项目摘要。这项调查的长期目标是开发解冻后评估的方法，允许移植地点在移植前评估脐带血单位(UCB)，并可被UCB银行用作其质量控制计划的一部分。脐血是造血干细胞(HSCs)的重要来源，用于治疗包括血癌在内的多种疾病。UCB目前占美国每年进行的所有造血干细胞移植的28%，迄今在全球范围内进行了14,000例人类移植。脐带血的优点有很多：可以在没有捐献者风险的情况下收集；立即可以在库中获得；可获得更广泛的各种人类白细胞抗原基因型，库中约有350,000个单位；较低的免疫反应性和固有的病原体传播。所有迹象表明，UCB的临床应用将继续增长。绝大多数的脐带血单位被收集并冷冻保存以供以后使用。已投入相当大的努力，通过标准化收集、处理和保存来提高联合信贷机构的质量。尽管在标准化化武处理方面作出了上述努力，但有报告称，化武处理单位解冻后恢复情况不佳。目前还没有一种标准的指标或衡量标准来量化UCB产品的解冻后效力。对脐血的移植研究表明，CD34+和集落形成单位(CFU)含量与植入和长期存活有关。这两种方法都是评估解冻后功能的候选方法。造血细胞产品表现出显著的细胞损失 来自解冻后的细胞凋亡。最近的研究表明，表达早期凋亡迹象的细胞不能移植到动物移植模型中，这表明细胞功能严重受损。因此，解冻后细胞凋亡的特征可能是临床上与解冻后脐带血质量相关的指标。解冻后的细胞凋亡也可能是细胞在储存过程中老化的一个标志。我们的假设是，解冻后的细胞凋亡测量可以作为脐带血单位在保存过程和储存过程中的损害的临床相关指标。