STTR Phase I: Novel Wicking Matrix Bioreactor for Pluripotent and Progenitor Cell Expansion

小型企业技术转让（STTR）项目的更广泛影响/商业潜力是开发一种生物反应器，可用于再生医学、组织工程和药物发现的细胞生产和扩增。虽然在多能干细胞培养和分化策略的制定方面取得了重大进展，但在将这些过程扩大到临床和研究应用所需的细胞数量方面存在重大差距。该项目的具体重点是扩大胰岛细胞治疗糖尿病的规模。糖尿病目前影响着全世界4亿人，每年导致500万人死亡。目前尚无治疗方法。可移植胰岛细胞的来源可以减轻许多糖尿病并发症，并恢复数百万人的生活质量。这个STTR一期项目建议开发和测试一种新型的抽吸生物反应器和生物工艺，用于扩增人类多能源β胰岛细胞。更具体地说，这将需要关注3个主要目标：i)通过化学和额外的细胞基质添加来优化排芯基质的纤维素表面，以确保胰岛细胞的附着和增殖；Ii)优化可控制的分化参数，如氧化水平和进料速率，使分化细胞增加10倍；iii)开发一种使用物理和生化手段从基质中去除分化细胞的过程，同时保持细胞在活力和表型方面的完整性。这些研究将作为组织工程和再生医学应用的生物反应器的原理证明。

The broader impact/ commercial potential of the Small Business technology Transfer (STTR) project is to develop a bioreactor that may be used for production and expansion of cells for regenerative medicine, tissue engineering, and drug discovery. While significant advances have been made in developing strategies for the culture and differentiation of pluripotent stem cells, there is a critical gap in scaling these processes up to the number of cells required for clinical and research applications. The specific focus of this project is the scale-up of beta islet cells for the treatment of diabetes. Diabetes currently affects 400 million people worldwide leading to 5 million deaths a year. There is currently no cure. A source of transplantable islet cells could alleviate many diabetic complications and restore the quality of life for millions of individuals.This STTR Phase I project proposes to develop and test a novel wicking bioreactor and bioprocess for expansion of human pluripotent-derived beta islet cells. More specifically, this will require focusing on 3 major objectives: i)Optimizing the cellulosic surface of the wicking matrix with chemical and extra cellular matrix additions to ensure attachment and proliferation of the islet cells; ii)optimizing controlled differentiation parameters such as oxygenation levels and feed rates to achieve a 10 fold increase in differentiated cells; and iii) develop a process using physical and biochemical means to remove the differentiated cells from the matrix while maintaining cellular integrity both in terms of viability and phenotype. These studies will serve as proof-of-principle of the proposed bioreactor for tissue engineering and regenerative medicine applications.