EXPANSION OF HUMAN UNBILICAL CORD BLOOD STEM CELLS

脐带血作为造血源的利用 干细胞移植一直受到脐带血细胞数量较少的限制。 样本。体外扩增CB细胞有可能克服这些问题 限制。Astrom已经开发出一种临床规模的自动化GMP细胞 生产系统(CPS)，可以成功地扩大CB样品。在……里面 第二阶段研究，建议进行临床试验，以测试安全性和 扩大的脐带血用于增加标准脐带血移植的疗效。在……里面 并行、CB扩展条件将优化以实现最大产出 原始的造血干细胞。文化变量的影响 例如细胞因子组合、辅助/基质细胞、接种密度 和中等灌流速率对CD34LIN细胞和LTC-IC产量的影响 将会被检查。使用优化的条件，维护 然后将使用体内实验确定造血细胞的再繁殖 NOD/SCID小鼠模型。根据第二阶段的结果，第三阶段的研究将 在干细胞中使用最佳扩增的CB进行临床试验 移植，采用修改后的增强方案或 替代战略。成功完成这些试验将导致 Astrom CPS用于CB细胞扩展的营销，潜在地 这导致了CB在干细胞移植中的更广泛使用。 建议的商业应用： 一个封闭的、自动化的、用于脐带血细胞扩增的GMP系统将是非常好的 价值。CB移植比BM或MPB移植有几个优势， 但目前受到可用电池数量的限制。CB电池 扩展将缓解这一限制，从而促进CB 包括造血干细胞在内的多种适应症的移植 移植和基因治疗。

The utilization of umbilical cord blood (CB) as a source of hematopoietic stem cells in transplantation has been limited by low cell numbers in CB samples. Expanding CB cells ex vivo can potentially overcome these limitations. Aastrom has developed a clinical-scale, automated, GMP cell production system (CPS) which can successfully expand CB samples. In Phase II studies, clinical trials are proposed to test the safety and efficacy of using expanded CB to augment standard CB transplants. In parallel, CB expansion conditions will be optimized for maximal output of primitive hematopoietic stem cells. The effects of culture variables such as cytokine combinations, accessory/stromal cells, inoculum density, and medium perfusion rates, on the output of CD34+lin- cells and LTC-IC will be examined. Using optimized conditions, the maintenance of hematopoietic repopulating cells will then be determined using an in vivo NOD/scid mouse model. Based on phase II results, phase III studies will pursue clinical trials using optimally expanded CB in stem cell transplants, employing either modified augmentation protocols or replacement strategies. Successful completion of these trials would lead to the marketing of the Aastrom CPS for CB cell expansion, potentially leading to more widespread use of CB in stem cell transplantation. PROPOSED COMMERCIAL APPLICATIONS: A closed, automated, GMP system for CB cell expansion would be of great value. CB transplants have several advantages over BM or mPB transplants, but are currently limited by the number of cells available. CB cell expansion would alleviate this limitation, thereby facilitating CB transplants for many indications including hematopoietic stem cell transplantation and gene therapy.