SBIR Phase II: Unique Biomaterial for Extended Culture, Expansion and Transduction of Hematopoietic Stem Cells in Vitro

*9800926 PYKETT这个小企业创新研究第二阶段项目将延长泡沫细胞造血干细胞培养系统的开发，以进行长期维护，旨在推进骨髓移植和造血干细胞基因治疗程序。第一阶段的研究表明，在不需要补充细胞因子的环境中，纤维泡沫能够在较长时间内保持和扩大原始的、多潜能的造血干细胞。在第一阶段研究确立的原则证明的基础上，第二阶段将通过解决以下具体目标来开发先进的纤维素泡沫应用：大规模纤维素泡沫-HSC培养系统的临床前优化；使用SCID小鼠动物模型评估大规模纤维素泡沫系统中培养的HSC的体内植入能力；检测在大规模纤维素泡沫系统中转导的HSC的转导率和体内植入能力。这项工作将展示纤维素泡沫在临床相关规模上促进多潜能造血干细胞在无细胞因子系统中延长存活、扩增和转导的能力，以增强骨髓移植和基因治疗，这是目前现有技术无法实现的目标，并将显著提高治疗各种造血疾病的能力。商业应用的目标是骨髓移植和造血疾病的基因治疗的临床市场。美国每年的骨髓移植市场规模为45亿美元，而造血干细胞基因治疗市场才刚刚兴起。***

*** 9800926 Pykett This Small Business Innovation Research Phase II project will extend the development of Cellfoam hematopoietic stem cell (HSC) culture systems for long-term maintenance aimed at advancing bone marrow transplantation and HSC gene therapy procedures. Phase I research demonstrated the ability of Cellfoam to maintain and expand primitive, multipotent HSCs for extended periods in an environment in which no supplemented cytokines are required. Building on the proof of principle established in Phase I research, Phase II will develop advanced Cellfoam applications by addressing the following specific aims: Pre-clinical optimization of large scale Cellfoam-HSC culture systems; Evaluation of the in vivo engraftment capabilities of HSCs cultured in large scale Cellfoam systems using a SCID mouse animal model; Examination of transduction rates and in vivo engraftment capabilities of HSCs transduced in large scale Cellfoam systems. This work will demonstrate the ability of Cellfoam to promote, on a clinically relevant scale, the extended survival, expansion and transduction of multipotent HSCs in a cytokine-free system for enhanced bone marrow transplantation and gene therapy, goals which are currently not possible with existing technologies and which would markedly enhance the ability to treat individuals with various hematopoietic disorders. Commercial applications are aimed at clinical markets for bone marrow transplantation and gene therapy of hematopoietic disorders. The annual US market for bone marrow transplantation stands at $4.5 billion; markets for HSC gene therapy are just emerging. ***