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，长期目标和具体目的是通过更好地了解脐带血细胞组成，改善接受同种异体血液移植的患者的结果。目的是通过互补的策略（例如脐带血细胞的离体扩张）以及前体细胞或联合血液单位的选定亚群的结合来增强脐带移植物。虽然使用脐带血移植导致选定患者的预后改善，但仍需要进行大量工作以改善所有患者的结果。需要立即改进的两个领域是植入和免疫重建的领域。 我们希望检验的主要假设是，干细胞数量增加（未分化或投入）是否会导致髓样和淋巴样恢复更快。使用离体扩展策略将使我们能够确定我们是否能够扩展多能干细胞以及临床使用的授权前体。该项目的发现将产生重要的影响，这将导致对项目I和III的进一步研究。尽管有数据表明，造血细胞数量越高，通过髓样更快的重建导致预后改善，但我们也特别对更快的淋巴样恢复感兴趣。我们的初步数据表明，CD34+细胞和CD4+细胞恢复之间的重要收集。特定的目标1表征脐带血单位，以确定整体，特别是淋巴前体含量。特定的目标2将定义和优化离体扩展条件。具体目标3将涉及对定义最有希望的条件的重要临床研究。特定的目标4将重点放在脐带血移植后临床免疫重建的速度和程度上。这些联合研究以及与项目I和III的广泛相互作用将使我们能够确定我们是否能够改善患者的临床结果。