Clinical studies of cord blood

脐带血的临床研究

• 批准号: 6594543
• 负责人: JOANNE KURTZBERG
• 金额: $ 41.84万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-05-01 至 2006-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6594543
• 关键词: CD34 molecule; CD4 molecule; NOD mouse; SCID mouse; blood treatment; cell population study; cell proliferation; cord blood; hematopoietic stem cells; hematopoietic tissue transplantation; homologous transplantation; human subject; human therapy evaluation; patient oriented research; stem cell transplantation; transplantation immunology

The broad, long-term objective and specific aims of this project are to improve the outcome of patients receiving allogeneic cored blood transplantation through a better understanding of the cord blood cell composition. The aims are to augment the cord blood graft through complementary strategies such as ex vivo expansion of cord blood cells and combination of selected sub-populations of precursor cells or combined blood units. While the use of cord blood transplantation has resulted in improved outcome in selected patients, there remains a significant amount of work that needs to be done to improve on the outcome for all patients. Two areas that need immediate improvement are those of engraftment and immune reconstitution. The major hypothesis we wish to test is whether increased numbers of stem cells (undifferentiated or committed) will result in a more rapid myeloid and lymphoid recovery. Using ex vivo expansion strategies will allow us to determine whether we will be able to expand pluripotent stem cells as well as committed precursors for clinical use. The findings in this project will have an important impact that will lead to further studies in projects I and III. While there are data to suggest that higher numbers of hematopoietic cells results in improved outcome through a more rapid myeloid reconstitution, we are specifically also interested in a more rapid lymphoid recovery. Our preliminary data suggests an important collection between CD34+ cells and CD4+ cell recovery. Specific aim 1 characterize the cord blood units to determine the overall and specifically lymphoid precursor content. Specific aim 2 will define and optimize ex vivo expansion conditions. Specific aim 3 will involve the important clinical studies of the most promising conditions defined. Specific aim 4 will focus on the pace and extent of clinical immune reconstitution following the cord blood transplantation. These combined studies and the extensive interactions with Project I and III, will allow us to determine whether we are able to improve the clinical outcome for our patients.

该项目的广泛，长期目标和具体目标是通过更好地了解脐带血细胞成分来改善接受异基因带芯血移植的患者的结局。目的是通过补充策略，如脐带血细胞的体外扩增和选定的前体细胞亚群或组合血液单位的组合来增强脐带血移植物。虽然脐带血移植的使用已经改善了某些患者的预后，但仍有大量的工作需要做，以改善所有患者的预后。需要立即改进的两个领域是植入和免疫重建。 我们希望检验的主要假设是，干细胞（未分化的或定向的）数量的增加是否会导致更快的骨髓和淋巴恢复。使用离体扩增策略将使我们能够确定我们是否能够扩增多能干细胞以及用于临床使用的承诺前体。该项目的研究结果将产生重要影响，导致项目一和项目三的进一步研究。虽然有数据表明，更多数量的造血细胞通过更快的骨髓重建导致改善的结果，但我们特别感兴趣的是更快的淋巴恢复。我们的初步数据表明，CD34+细胞和CD4+细胞恢复之间的重要集合。具体目标1表征脐带血单位，以确定总体和特定淋巴前体含量。具体目标2将定义和优化离体扩增条件。具体目标3将涉及所定义的最有希望的条件的重要临床研究。具体目标4将关注脐带血移植后临床免疫重建的速度和程度。这些联合研究以及与项目I和III的广泛互动将使我们能够确定我们是否能够改善患者的临床结局。