EXPANSION OF HUMAN UNBILICAL CORD BLOOD STEM CELLS

脐带血（CB）作为造血资源的利用

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.