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）可以用作缺乏相关供体但本质上低细胞剂量的患者的替代移植物，导致植入延迟和移植失败严重限制了对这一宝贵资源的更广泛使用。因此，项目1的中心假设是CB祖细胞在间充质干细胞上的离体扩展（MSC）将提供比未经操纵的CB细胞更快的造血再耐药，植入率较少。实际上，我们开发的CB单核细胞/MSC共培养系统应避免我们在早期的液体悬浮培养研究中经历的明显的CD34+细胞损失，并且因为它为CB祖细胞的繁殖提供了替代的生态位，应产生CB细胞扩张的总体扩张。该预测将在1期临床试验中对接受CB移植的血液学恶性肿瘤（AIM 1.1）的患者进行测试，并与机械研究相结合，以确定特定CB是否抑制了最佳扩张。