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

小型企业技术转移(STTR)项目更广泛的影响/商业潜力是开发一种生物反应器，可用于生产和扩大再生医学、组织工程和药物发现的细胞。虽然在开发多能干细胞培养和分化策略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仍存在严重差距。该项目的具体重点是扩大胰岛细胞用于治疗糖尿病的规模。糖尿病目前影响全球4亿人，每年导致500万人死亡。目前还没有治愈的方法。一种可移植的胰岛细胞来源可以缓解许多糖尿病并发症，并恢复数百万人的生活质量。这项STTR第一阶段项目建议开发和测试一种新的纤吸生物反应器和生物工艺，用于扩增人类多能性来源的胰岛细胞。更具体地说，这将需要专注于三个主要目标：i)通过添加化学和细胞外基质来优化芯子基质的纤维表面，以确保胰岛细胞的附着和增殖；ii)优化受控的分化参数，如氧合水平和进料速度，以实现已分化细胞的10倍增长；以及iii)开发一种使用物理和生化手段从基质中去除已分化细胞的过程，同时保持细胞活力和表型的完整性。这些研究将作为拟议的生物反应器在组织工程和再生医学应用中的原则证明。

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.