SBIR Phase II: Selection and Storage of Hematopoietic Stem Cells in a Novel Bioreactor

这个小型企业创新研究第二阶段项目将利用Cytomatrix的三维生物基质CellFoam作为干细胞冷冻保存系统的基础，该系统在单个集成设备中预先选择和冷冻保存造血祖细胞(HPC)。第一阶段的研究表明，在预培养过程中，纤维泡沫可以促进未分离的、Ficoll纯化的单个核细胞和CD34+细胞中的HPC的浓缩，并在冷冻保存期间保持其活性和功能。在这些可行性研究结果的基础上，第二阶段将开发一个纤维素泡沫低温保存原型，以解决以下目标：1)优化预培养试剂，包括培养基；2)优化冷冻保存方案，包括低温保存溶液；3)使用NOD/SCID小鼠模型评估HPC在体内的植入能力。这项工作将展示纤维素泡沫促进HPC浓缩和冷冻保存的能力，用于临床应用，如长期干细胞存储和骨髓移植，目前的方法对这些应用并不是最佳的。用于HPC的第一个综合选择、储存和改性系统的纤维泡沫系统有望商业化，以满足脐带血储存、骨髓移植和基因治疗不断增长的市场的需求。预计未来十年，这些市场的年销售额将超过6亿美元。

This Small Business Innovation Research Phase II project will utilize Cytomatrix's three-dimensional biomatrix, Cellfoam, as the foundation of a stem cell cryopreservation system that pre-selects and cryopreserves hematopoietic progenitor cells (HPCs) in a single, integrated device. Phase I research demonstrated that Cellfoam mediates the enrichment of HPCs from unfractionated, ficoll purified mononuclear, and CD34+ selected cells during pre-culture and maintains their viability and functional capacity during cryopreservation. Building on these feasibility findings, Phase II will develop a Cellfoam cryopreservation prototype by addressing the following aims: 1) Optimization of pre-culture reagents, including culture media; 2) Optimization of cryopreservation protocols, including cryopreservation solutions; 3) Evaluation of the in vivo engraftment capabilities of HPCs using an NOD/SCID mouse model. The work will demonstrate the ability of Cellfoam to foster HPC enrichment and cryopreservation for clinical applications, such as long-term stem cell storage and bone marrow transplantation, for which current approaches are not optimal. Commercialization of Cellfoam systems for the first-ever integrated selection, storage and modification system for HPCs is anticipated to meet the needs of growing markets in cord blood storage, bone marrow transplantation and gene therapy. The markets are forecast to exceed US$600 million annually in the next decade.