SBIR Phase II: Clinical-Scale Suspension Bioreactor for Primary Hematopoietic Culture

这个小型企业创新研究第二阶段项目描述了一个一次性的，高效的悬浮生物反应器的初级造血（血细胞形成）细胞培养的发展。这些培养物的独特挑战（异质性、供体可变性和剪切敏感性）使得传统的烧瓶或悬浮培养物不能经济地且一致地产生大量细胞。在第一阶段，一次性悬浮生物反应器的可行性和特点进行了证明。在第II阶段，将构建、表征并测试用于临床使用（干细胞移植）的大型搅拌一次性生物反应器的放大原型的可靠性和耐久性。在第一阶段建立的气体和质量传递相关性将得到验证和扩展。将研究使用培养基光密度作为细胞密度的替代测量，最终产品将是一个系统，该系统将烧瓶培养的简单、一次性性质与悬浮生物反应器的控制和监测能力相结合。由此产生的系统将能够成本有效地生产大量的原代造血细胞，并将提高移植、免疫治疗和基因治疗领域的医疗程序的有效性并降低其成本。

This Small Business Innovation Research Phase II project describes thedevelopment of a disposable, highly efficient suspension bioreactor for primary hematopoietic (blood cell-forming) cell culture. The unique challenges (heterogeneous nature, donor variability, and shear-sensitivity)of these cultures render traditional flask or suspension cultures unable to economically and consistently produce large quantities of cells. In Phase I, the feasibility and characteristics of a disposable suspension bioreactor was demonstrated. In Phase II, a scaled-up prototype of a large, agitated disposable bioreactor designed for clinical use (stem cell transplantation) will be constructed, characterized, and tested for reliability and durability. Gas and mass transfer correlations established in Phase I will be verified and extended. The use of medium optical density as a surrogate measure for cell density will be investigated.The final product will be a system that combines the simple, disposable nature of flask culture with the control and monitoring capabilities of a suspension bioreactor. The resulting system will enable the cost-effective production of large numbers of primary hematopoietic cells and will improve the effectivenessand decrease the cost of medical procedures in the fields of transplantation, immunotherapy, and gene therapy.