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。这项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)，并可由 UCB 银行用作其质量控制计划的一部分。 UCB 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。目前，UCB 占美国每年进行的所有 HSC 移植手术的 28%，迄今为止，全世界已进行了 14,000 例人类移植手术。 UCB 的优点有很多：可以在对捐赠者没有风险的情况下收集它；银行可立即提供服务；多样化 HLA 基因型的更广泛可用性，已储存约 350,000 个单位；较低的免疫反应性和较低的固有病原体传播。所有迹象都表明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。我们投入了大量精力，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 加工方面做出了上述努力，但有报道称 UCB 装置解冻后恢复情况不佳。目前尚无量化 UCB 产品解冻后功效的标准指标或措施。 UCB 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相关。这两种测定都是评估解冻后功能的候选方法。造血细胞产品表现出显着的细胞损失 来自解冻后的细胞凋亡。最近的研究表明，表达细胞凋亡早期迹象的细胞没有植入动物移植模型中，这表明细胞存在显着的功能损伤。因此，表征解冻后细胞凋亡可能是临床相关的 UCB 解冻后质量指标。解冻后细胞凋亡也可能是储存过程中细胞老化的标志。我们假设解冻后细胞凋亡测量可以作为 UCB 单位保存过程和储存过程中损伤的临床相关指标。