Notch Mediated Expansion of Hematopoietic Precursors

描述（由申请人提供）： 本R24申请的目标是建立一种资源，该资源将提供临床级试剂和方法，用于人造血再生细胞的离体扩增，以改善脐带血移植。 脐带血已被确定为需要干细胞移植的患者的替代干细胞来源，这些患者没有其他合适的供体。 然而，由于干细胞数量不足，结果受到限制，导致植入延迟，这通常与致命感染有关。 最近，我们的实验室开发了新的方法，使用Noth ligan，一种已知的细胞命运决定调节剂，以提高脐带血前体细胞的再生能力。 因此，为了将这些发现扩展到临床并为未来的临床试验提供资源，我们建议优化这些用于扩增脐带血前体细胞的方法，并开发符合cGMP的程序方法并制备临床试验所需的临床级试剂。 这些目标的成功完成将为未来的努力奠定基础，以确定我们在I期临床试验中方法的可行性和安全性，然后提供cGMP试剂和程序作为多机构II期和III期试验的资源。

DESCRIPTION (provided by applicant): The goal of this R24 application is to establish a resource that will provide clinical grade reagents and methods for ex vivo expansion of human hematopoietic repopulating cells to improve cord blood transplantation. Umbilical cord blood has been established as an alternative source of stem cells for patients in need of stem cell transplantation who do not have an otherwise suitable donor identified. However, results have been limited due to inadequate stem cell numbers, leading to delayed engraftment that is often associated with lethal infection. Recently, our laboratory has developed novel methods, using Noth ligan, a known regulator of cell fate determination, to enhance the repopulating capacity of cord blood precursor cells. Thus, to extend these findings into the clinic and provide a resource for future clinical trials, we propose to optimize these methods for expanding cord blood precursor cells, and to develop cGMP compliant procedures methods and prepare the clinical grade reagents necessary for clinical trials. Successful completion of these aims will provide the basis for future efforts to establish the feasibility and safety of our approach in a phase I clinical trial, and then to provide the cGMP reagents and procedures as a resource for multi-institutional phase II and III trials.