EX VIVO EXPANDED CORD BLOOD CELLS

体外扩增脐带血细胞

• 批准号: 6794065
• 负责人: IAN K MCNIECE
• 金额: $ 44.15万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-02-07 至 2006-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6794065
• 关键词: NOD mouse; SCID mouse; T lymphocyte; clinical research; colony stimulating factor; cord blood; flow cytometry; hematopoietic stem cells; homologous transplantation; human subject; human therapy evaluation; interleukin 3; interleukin 6; leukemia; megakaryocytes; neoplasm /cancer relapse /recurrence; neoplasm /cancer therapy; neutrophil; stem cell factor; stem cell transplantation; tissue /cell culture

Many cancer patients who are candidates for high dose chemotherapy do not have available a suitable related or unrelated donor of bone marrow or peripheral blood progenitor cells. Human umbilical cord blood (CB) is a unique source of transplantable hematopoietic cells that offers an alternative source of hematopoietic cells for these patients. The use of CB cells to date, has primarily been limited to small pediatric patients due to the low cell numbers in CB products. The focus of this proposal is to optimize ex vivo culture of CB to provide increased numbers of cells to enable the use of CB in adult patients. In addition, optimization of the expansion cultures will enable more rapid hematopoietic and immune recovery post transplant and potentially minimize other complications associated with transplantation of CB. The first aim of these studies is to evaluate improved expansion culture conditions in clinical trials. Preclinical studies will also be performed to evaluate other culture conditions that may provide enhanced platelet recovery. In addition, analysis will be performed of primitive cells in the expanded products as an indication of the effect of expansion on long term engrafting cells (stem cells). The second aim will optimize transduction cultures of expanded cells and subsequent clinical studies will incorporate these conditions to use marked expanded cells in patients. This will allow the evaluation of the contribution of expanded cells to long to engraftment. Correlative analysis will be performed comparing the contribution of the marked cells in patients with in vitro assays of primitive progenitor cells to determine the predictive value of the in vitro assays. The third aim will evaluate the immune recovery in patients receiving ex vivo expanded cells. Both phenotypical and functional analysis of T cells subsets will be performed The final goal of these studies is to determine culture conditions for the expansion of T cells in vitro for use a source of donor lympohocytes to induce an anti tumor effect in patients who relapse. In the absence of cultured T cells the patients who relapse have no alternate source of donor lymphocytes and would die from disease progression. The outcome of these studies will provide us with a better understanding of the potential clinical utility of CB. Optimal expansion cultures will enable the use of CB in adults and provide more rapid engraftment. Overall these studies will lead to improved outcome in these patients.

许多候选高剂量化疗的癌症患者没有适当的相关或无关的骨髓或外周血祖细胞的供体。人脐带血（CB）是可移植造血细胞的独特来源，为这些患者提供造血细胞的替代来源。迄今为止，由于CB产物中细胞数量低，CB细胞的使用主要仅限于小儿科患者。该提案的重点是优化CB的离体培养物，以提供更多的细胞数量，以便在成年患者中使用CB。此外，扩张培养物的优化将使移植后更快的造血和免疫恢复能够最大程度地减少与CB移植有关的其他并发症。这些研究的第一个目的是评估临床试验中改善的扩张培养条件。还将进行临床前研究，以评估可能提供增加血小板恢复的其他培养条件。此外，将对扩展产物中的原始细胞进行分析，以表明扩展对长期植入细胞（干细胞）的影响。第二个目的将优化扩展细胞的转导培养物，随后的临床研究将结合这些疾病以使用患者的明显扩展细胞。这将允许评估扩展的细胞对长期植入的贡献。将进行相关分析，以比较原始祖细胞的体外测定患者中明显细胞的贡献，以确定体外测定的预测价值。第三个目标将评估接受过体内扩张细胞的患者的免疫恢复。 T细胞亚群的表型和功能分析都将进行这些研究的最终目标是确定T细胞在体外扩展的培养条件，用于使用供体淋巴细胞的来源，以诱导复发的患者诱导抗肿瘤效应。在没有培养的T细胞的情况下，复发的患者没有供体淋巴细胞的其他来源，并且会死于疾病进展。这些研究的结果将使我们更好地了解CB的潜在临床实用性。最佳扩展培养物将使CB在成人中使用，并提供更快的植入。总体而言，这些研究将导致这些患者的结果改善。