A NOVEL FROZEN-STORAGE SYSTEM FOR CORD BLOOD STEM CELLS

本研究的总体目标是开发一种用于冷冻保存和储存人胎盘/脐带血（PCB）来源的造血祖细胞（CD 34+）的改进系统，特别是因为它涉及改善冷冻/解冻细胞的正常结构和功能的保留，从而改善临床结局（植入）。随着针对基础研究（例如，造血早期事件的研究）或临床应用（例如，用于骨髓移植的肿瘤细胞清除和T细胞去除，子宫内干细胞移植和基因治疗的发展以纠正遗传疾病等），对于开发用于这些纯化和/或体外扩增的细胞的改进的保存方法以提供“细胞库”存在相关的增加的需求。此外，随着纯化祖细胞在同种异体移植物中活性的增加，疾病传播的可能性（例如，HIV和B和C型肝炎病毒）的感染，要求在此类程序中仅使用来自感染性疾病筛选的供体材料的细胞。储存冷冻祖细胞的能力将允许有足够的时间进行适当的筛选。本提案的目标是使用新的许可技术并基于合理的生物物理细胞类型特异性特征和数学建模技术来开发封闭的冷冻保存、储存和洗涤系统，这将允许高效且安全地使用冷冻保存的PCB衍生的造血祖细胞。拟议的商业应用：这项研究将为人类PCB提供一个完整的冷冻保存系统，使冷冻保存材料的有效利用和广泛的商业应用在血库操作。该系统的一个特别重要的方面是，它将允许从冷冻，储存，解冻和多氯联苯单位在一个单一的封闭系统输血的完整过程，而无需离心洗涤。

The overall goal of this research is to develop an improved system for cryopreservation and storage of human placental/umbilical cord blood (PCB) derived hematopoietic progenitor cells (CD34+), especially as it relates to improving the retention of normal structure and function of frozen/thawed cells and thereby improve clinical outcome (engraftment). With increasing effort directed toward purification and/or in vitro expansion of CD34+ cells for either fundamental research (e.g. research of early events in hematopoiesis) or clinic applications (e.g.,tumor cell purging and T-cell depletion for bone marrow transplantation, development of in utero stem cell transplantation and gene therapy to correct genetic disorders, etc.), there is an associated, increased need for the development of improved preservation methods for these purified and/or in vitro expanded cells to provide "cell banks". In addition, with the increased activity in allograft of purified progenitor cells, the possibility of disease transmission (e.g., HIV and the hepatitis B and C viruses) from use of contaminated donor material requires that only cells from infectious disease-screened donor material be used in such programs. The ability to store frozen progenitor cells would allow sufficient time for adequate screening to be performed. It is the goal of this proposal to develop a closed cryop reservation, storage, and washing system, using novel licensed technology and based on sound biophysical cell-type specific characteristics and mathematical modeling techniques, which will allow efficient and safe use of cryopreserved PCB derived hematopoietic progenitor cells. PROPOSED COMMERCIAL APPLICATIONS: This research will provide a complete cryopreservation system for human PCB that will allow efficient use of cryopreserved material and widespread commercial application in blood bank operations. A particularly important aspect of this system is that it will allow the complete process from freezing, storage, thawing, and transfusion of PCB units in a single closed system, without centrifugal washing.