CAN THE OXYGEN TENSION IN A MICROFLUIDIC STEM CELL CULTURE DEVICE BE PRECISELY CONTROLLED DURING BOTH CONTINUOUS AND INTERMITTENT MEDIA EXCHANGE?

在连续和间歇培养基交换过程中，微流控干细胞培养装置中的氧张力能否得到精确控制？

• 批准号: EP/I005471/1
• 负责人: Nicolas Szita
• 金额: $ 12.76万
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2010
• 资助国家: 英国
• 起止时间: 2010 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FI005471%2F1
• 关键词: OXYGEN; TENSION; MICROFLUIDIC; STEM; CELL

Therapies using human cells have great promise for addressing serious medical conditions for which we lack effective treatments. These include particularly those chronic degenerative diseases of old age such as stroke, heart failure, age-related blindness and later stages of both insulin dependent diabetes and Parkinson's disease. In particular, stem cells that can be converted to a variety of specialised cells are especially important. The chemical, biological and physical cues needed for such conversions are complex and it is necessary to examine a large number of permutations to achieve a good outcome. Because many of the biochemical cues required are of very high cost, even basic discovery research and early translational studies in culture flasks are often restricted such that optimal conditions can be missed. In principle it is possible to address this problem by smaller and smaller flasks but in practice the necessary manipulations including removal of spent nutrient and the addition of fresh nutrient becomes difficult to manage. The proposed research addresses this by using micro-fabrication methods to create chambers with gas permeable membranes to provide the oxygen cells need. We will use such microfluidic systems and further develop them to enable best possible control over oxygen which is an important cue for the conversion from stem cells to specialised cells. The project will provide the foundation for a technology with which it will ultimately be possible to achieve more rapid and comprehensive examination of the best conditions for human cell culture to produce the quantities needed for both basic and applied research. Because mouse stem cells are particularly well defined they will be used in this study as a surrogate for human cells to establish the proof of principle.

使用人类细胞的疗法在解决我们缺乏有效治疗方法的严重疾病方面有很大的希望。这些疾病特别包括老年慢性退行性疾病，如中风、心力衰竭、与年龄有关的失明以及胰岛素依赖型糖尿病和帕金森病的晚期。特别是，可以转化为各种特化细胞的干细胞尤为重要。这种转化所需的化学、生物和物理线索是复杂的，必须检查大量的排列才能取得良好的结果。由于所需的许多生化线索的成本非常高，甚至在培养瓶中进行的基础发现研究和早期转化研究也经常受到限制，从而可能错过最佳条件。原则上，通过越来越小的烧瓶可以解决这个问题，但在实践中，必要的操作，包括去除废营养物质和添加新鲜营养物质变得难以管理。提出的研究解决了这个问题，通过使用微制造方法来制造带有气体渗透膜的腔室，以提供所需的氧气细胞。我们将使用这种微流体系统，并进一步开发它们，以实现对氧气的最佳控制，这是干细胞向特化细胞转化的重要线索。该项目将为一项技术奠定基础，有了这项技术，最终有可能更迅速和全面地检查人类细胞培养的最佳条件，以产生基础研究和应用研究所需的数量。由于小鼠干细胞的定义特别明确，因此它们将在本研究中用作人类细胞的替代品，以建立原理证明。

项目成果

Removal and dispersal of biofluid films by powered medical devices: Modeling infectious agent spreading in dentistry.

• DOI: 10.1016/j.isci.2021.103344
• 发表时间: 2021-11-19
• 期刊: iScience
• 影响因子: 5.8
• 作者: Eames I;D'Aiuto F;Shahreza S;Javanmardi Y;Balachandran R;Hyde M;Ng YL;Gulabivala K;Watson S;Davies H;Szita N;Khajeh J;Suvan J;Moeendarbary E
• 通讯作者: Moeendarbary E

Stem Cell Manufacturing

干细胞制造

• DOI: 10.1016/b978-0-444-63265-4.00008-x
• 发表时间: 2016
• 作者: Marques M

Robust, microfabricated culture devices with improved control over the soluble microenvironment for the culture of embryonic stem cells.

• DOI: 10.1002/biot.201300245
• 发表时间: 2014-06
• 期刊: Biotechnology journal
• 影响因子: 4.7
• 作者: Macown RJ;Veraitch FS;Szita N
• 通讯作者: Szita N

Automated and online characterization of adherent cell culture growth in a microfabricated bioreactor.

• DOI: 10.1177/2211068214529288
• 发表时间: 2014-10
• 期刊: Journal of laboratory automation
• 作者: Jaccard N;Macown RJ;Super A;Griffin LD;Veraitch FS;Szita N
• 通讯作者: Szita N

Quantifying cell-generated forces: Poisson's ratio matters.

• DOI: 10.1038/s42005-021-00740-y
• 发表时间: 2021-11-04
• 期刊: Communications physics
• 影响因子: 5.5
• 作者: Javanmardi Y;Colin-York H;Szita N;Fritzsche M;Moeendarbary E
• 通讯作者: Moeendarbary E