Cord Blood Expansion and Homing to Improve Engraftment

脐带血（CB）可以作为缺乏匹配的相关供体的患者的替代移植物，但固有的低细胞剂量导致延迟植入和移植失败严重限制了这种宝贵资源的广泛使用。因此，项目1的中心假设是在间充质干细胞（MSC）上离体扩增的CB祖细胞将提供比未操作的CB细胞更快速的造血重建以及更少的植入失败。事实上，我们已经开发的CB单核细胞/MSC共培养系统应该避免我们在早期液体悬浮培养研究中经历的显著的CD 34+细胞损失，并且因为它为CB祖细胞的繁殖提供了替代生态位，所以应该总体上产生改善的CB细胞扩增。这一预测将在接受CB移植治疗恶性血液病的患者中进行1期临床试验（目标1.1），并结合机制研究，以确定特定CB是否抑制最佳扩增

Umbilical cord blood (CB) can serve as an alternative graft for patients lacking a matched related donor, yet intrinsically low cell doses leading to delayed engraftment and graft failure severely restrict wider use of this valuable resource. Hence, the central hypothesis of Project 1 is that CB progenitors expanded ex vivo on mesenchymal stem cells (MSCs) will provide more rapid hematopoietic reconsititution, as well as less engraftment failure, than unmanipulated CB cells. Indeed, the CB mononuclear cell/MSC co-culture system we have developed should avoid the significant CD34+ cell losses we experienced in earlier liquid suspension culture studies and, because it provides a surrogate niche for the propagation of CB progenitors, should yield improved CB cell expansion overall. This prediction will be tested in a phase 1 clinical trial in patients undergoing CB transplantation for hematologic malignancies (Aim 1.1), coupled with mechanistic studies to determine if optimal expansion is inhibited by specific CB