Clinical studies of cord blood

该项目广泛的、长期的目标和具体的目标是通过更好地了解脐带血的组成来改善接受异基因脐带血移植的患者的预后。其目的是通过补充策略来扩大脐带血移植，例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。虽然脐带血移植的使用改善了选定患者的预后，但仍有大量工作需要做，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，干细胞数量的增加(未分化或定向)是否会导致更快的髓系和淋巴系恢复。使用体外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的承诺前体。这个项目的发现将产生重要的影响，将导致项目I和项目III的进一步研究。虽然有数据表明，更多的造血细胞会通过更快的髓系重建而改善预后，但我们也特别对更快的淋巴系恢复感兴趣。我们的初步数据表明，CD34+细胞和CD4+细胞恢复之间存在着重要的联系。具体目标1确定脐带血单位的特征，以确定总体和特定的淋巴前体含量。具体目标2将定义和优化体外扩增条件。具体目标3将涉及对确定的最有希望的情况进行重要的临床研究。具体目标4将侧重于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和项目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果。

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.