High-throughput stem cell bioprocess design - environmental influences on pluripotent stem cell expansion and differentiation

高通量干细胞生物工艺设计——环境对多能干细胞扩增和分化的影响

• 批准号: 239083-2011
• 负责人: Kallos, Michael
• 金额: $ 2.91万
• 依托单位: University of Calgary
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2014
• 资助国家: 加拿大
• 起止时间: 2014-01-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=547198
• 关键词: throughput; stem; cell; bioprocess; design

Regenerative medicine is a rapidly growing billion dollar multidisciplinary field at the intersection of medicine, engineering and science. It aims to create living, functional tissues that can repair or replace damaged, diseased or aging tissues or organs. Stem cells are critical to the success of regenerative medicine therapies, and what are needed are technologies to bridge the gap between basic biology and the clinical application of stem cells. The proposed research program will accelerate the development of these technologies, specifically targeting a reliable, reproducible way to grow stem cells to build tissues. The research will focus on pluripotent stem cells as they have the potential to generate any cell type in the body, i.e. large numbers of specialized (differentiated) cells. They can be derived from the inner cell mass of an early development blastocyst (embryonic stem cells) or from adult cells such as skin cells that are modified by the addition of key factors to be pluripotent (induced pluripotent stem cells). One of the major stumbling blocks on the road to effective regenerative medicine treatments is the limited number of available donor cells, and the small-scale, labour-intensive methods for culturing and differentiating them. The primary objective of the proposed research is to develop engineering methods and technology for efficiently growing human pluripotent stem cells in computer-controlled bioreactors. First, the effect of key bioreactor conditions (such as oxygen level) and the transport of nutrients will be examined for individual stem cell clusters and entire bioreactors. Second, new technology will be developed to accelerate the development of bioprocesses through the use of multiple smaller bioreactors as high-throughput tools to study many conditions quickly. The long term outcomes include innovative bioprocess designs, as well as critical knowledge of how output parameters (i.e. cell type, behaviour) are influenced by cell processing parameters (i.e. bioreactor oxygen level). This is fundamentally necessary for the regulatory approval and clinical application of stem cell technologies, including the generation and transplantation of cells/tissues for the treatment of human ailments (i.e. stroke, Parkinson's disease, diabetes).

再生医学是在医学，工程和科学的交叉点上快速增长的十亿美元多学科领域。 它旨在创建可以修复或替代受损，患病或衰老的组织或器官的活性组织。 干细胞对于再生医学疗法的成功至关重要，需要什么是弥合基本生物学和干细胞临床应用之间差距的技术。 拟议的研究计划将加速这些技术的发展，特别是针对一种可靠的，可再现的方法来种植干细胞建立组织的方法。该研究将集中在多能干细胞上，因为它们具有产生体内任何细胞类型的潜力，即大量的专门（分化）细胞。 它们可以源自早期发育胚泡（胚胎干细胞）的内部细胞质量，也可以源自成年细胞，例如通过添加要多能的关键因素（诱导多能性干细胞）来修饰的皮肤细胞。有效再生医学治疗的道路上的主要绊脚石之一是可用的供体细胞数量有限，以及用于培养和区分它们的小规模，劳动密集型方法。拟议研究的主要目的是开发工程方法和技术，以在计算机控制的生物反应器中有效地生长人类多能干细胞。首先，将检查单个干细胞簇和整个生物反应器的关键生物反应器条件（例如氧水平）和营养素的运输的影响。其次，将开发新的技术，以加快通过使用多个较小的生物反应器作为高通量工具来快速研究许多条件的生物过程的开发。长期结果包括创新的生物普应设计，以及有关输出参数（即细胞类型，行为）如何受细胞处理参数（即生物反应器氧水平）影响的关键知识。这对于干细胞技术的监管批准和临床应用是必不可少的，包括用于治疗人类疾病的细胞/组织的产生和移植（即中风，帕金森氏病，糖尿病）。