Cord Blood Expansion and Homing to Improve Engraftment

脐带血扩张和归巢以改善植入

• 批准号: 8555381
• 负责人: Elizabeth J Shpall
• 金额: $ 53.44万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-22 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8555381
• 关键词: Adult; Blood Cells; Blood Platelets; Bone Marrow; CD34 gene; Cells; Coculture Techniques; Coupled; Disadvantaged; Dose; Engraftment; Erythrocytes; Failure; Hematologic Neoplasms; Hematopoiesis; Hematopoietic; Hemorrhage; Homing; Infection; Leukocytes; Liquid substance; Mesenchymal Stem Cells; Methods; Mononuclear; Oxygen; Patients; Phase I Clinical Trials; Recovery; Resources; Suspension Culture; System; Testing; Therapeutic; Transplant Recipients; Transplantation; Umbilical Cord Blood; Umbilical Cord Blood Transplantation; base; experience; fighting; graft failure; improved; migration; prevent; progenitor; reconstitution; success

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

脐带血（CB）可以作为缺乏匹配相关供体的患者的替代移植物，但本质上较低的细胞剂量会导致移植延迟和移植失败，严重限制了这一宝贵资源的更广泛使用。因此，项目 1 的中心假设是，与未操作的 CB 细胞相比，在间充质干细胞 (MSC) 上离体扩增的 CB 祖细胞将提供更快的造血重建，以及更少的植入失败。事实上，我们开发的 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着 CD34+ 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，所以应该产生改进的 CB 细胞整体扩张。这一预测将在接受 CB 移植治疗血液恶性肿瘤的患者中进行 1 期临床试验（目标 1.1）进行测试，并结合机制研究以确定特定 CB 是否会抑制最佳扩张