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

STTR 第一阶段：用于多能细胞和祖细胞扩增的新型芯吸基质生物反应器

• 批准号: 1722384
• 负责人: Vinit Saxena
• 金额: $ 22.5万
• 依托单位: Sepragen Corporation
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-06-15 至 2018-11-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1722384&HistoricalAwards=false
• 关键词: STTR; Phase; Novel; Wicking; Matrix

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.

小企业技术转让（STTR）项目更广泛的影响/商业潜力是开发一种生物反应器，可用于再生医学，组织工程和药物发现的细胞生产和扩增。 虽然在开发多能干细胞的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存在关键差距。 该项目的具体重点是扩大β胰岛细胞治疗糖尿病的规模。糖尿病目前影响全球4亿人，每年导致500万人死亡。目前没有治愈方法。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。STTR第一阶段项目提出开发和测试一种新的毛细生物反应器和生物过程，用于扩增人多能性胰岛β细胞。更具体地，这将需要集中于3个主要目标：i）用化学和细胞外基质添加物优化芯吸基质的纤维素表面，以确保胰岛细胞的附着和增殖; ii）优化受控的分化参数，例如氧合水平和进料速率，以实现分化细胞的10倍增加;和iii）开发一种使用物理和生物化学手段从基质中除去分化细胞同时保持细胞在活力和表型方面的完整性的方法。 这些研究将作为组织工程和再生医学应用的拟议生物反应器的原理证明。