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.

小型企业技术转移（STTR）项目的更广泛的影响/商业潜力是开发一种生物反应器，该生物反应器可用于生产和扩展用于再生医学，组织工程和药物发现的细胞。 尽管在制定多能干细胞的培养和分化策略方面取得了重大进展，但将这些过程扩展到临床和研究应用所需的细胞数量时，存在危险的差距。 该项目的具体重点是β小岛细胞的扩大用于治疗糖尿病。目前，糖尿病在全球影响4亿人，每年可死亡500万人。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个个人的生活质量。该STTR I期项目提议开发和测试一种新型的Wicking Bioreactor和Bioprocess，以扩大人类多能衍生的Beta beta islet细胞。更具体地说，这将需要关注3个主要目标：i）使用化学和额外的细胞基质添加芯片矩阵的纤维素表面，以确保胰岛细胞的附着和增殖； ii）优化受控分化参数，例如氧合水平和进料速率，以使分化细胞的10倍增加； iii）使用物理和生化手段开发一个过程，以从基质中去除分化细胞，同时在生存力和表型方面保持细胞完整性。 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则证明。