EXPANSION OF HUMAN UNBILICAL CORD BLOOD STEM CELLS

脐带血作为造血干细胞来源的应用 干细胞在移植中受到CB中低细胞数量的限制 样品离体扩增CB细胞可以潜在地克服这些问题。 局限性。Aastrom开发了一种临床规模的自动化GMP细胞 生产系统（CPS），可以成功扩展CB样本。在 II期研究、临床试验拟用于测试安全性和 使用扩展CB增强标准CB移植的有效性。在 并行地，CB扩展条件将被优化以获得最大输出 原始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 和中等灌注率，对CD 34 +lin-细胞和LTC-IC的输出 将被审查。 使用优化的条件， 然后使用体内免疫细胞化学法测定造血再生细胞 NOD/scid小鼠模型。根据II期研究结果，III期研究将 在干细胞中使用最佳扩增的CB进行临床试验 移植，采用改良的扩增方案或 替代战略。这些审判的成功完成将导致 用于CB细胞扩增的Aastrom CPS的市场化， 导致CB在干细胞移植中的更广泛使用。 拟议的商业应用： 一个封闭的，自动化的，GMP系统的CB细胞扩增将是伟大的 值CB移植与BM或mPB移植相比具有几个优点， 但是当前受到可用小区数量的限制。CB细胞 扩展将缓解这一限制，从而促进CB 用于多种适应症的移植，包括造血干细胞 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.