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允许移植部位的移植点评估的方法，以评估移植前的脐带血单位（UCB），并可以由UCB银行用作其质量控制计划的一部分。 UCB是用于治疗包括血液癌在内的多种疾病的造血干细胞（HSC）的重要来源。 UCB现在占美国每年在美国进行的所有HSC移植物的28％，迄今为止在全球人类进行的14,000次移植。 UCB的优势很多：可以对捐助者无风险收集；银行立即供应；大约350,000个单位的多种HLA基因型的可用性更广泛；降低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单元都是收集和冷冻保存的，以供以后使用。通过标准化收集，处理和保存，已经投入了大量努力来提高UCB单元的质量。尽管在标准化UCB处理方面做出了上述努力，但有报道称UCB单元的融化后恢复不良。目前尚无标准度量或量度来量化UCB产品的后效力。 UCB的移植研究表明，CD34+和菌落形成单元（CFU）含量均与植入和长期生存有关。这两种测定法都是评估截止后功能的候选者。造血细胞产物表现出明显的细胞损失，导致 来自诊断后的细胞凋亡。最新的研究表明，表达凋亡早期迹象的细胞并未在动物移植模型中植入，表明细胞的功能障碍很大。因此，表征后凋亡的表征可能是UCB临床相关的诊断后质量指标。解冻后的凋亡也可能是储存过程中细胞衰老的标志物。我们的假设是，在保存过程和储存UCB单元期间，诊断后的凋亡措施可能是临床上相关的损害指标。