Use of bioactive polymers to regulate differentiation of embryonic stem cells in three-dimensional bioreactors

利用生物活性聚合物调控三维生物反应器中胚胎干细胞的分化

• 批准号: BB/D014824/1
• 负责人: Leonard Seymour
• 金额: $ 53.98万
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2006
• 资助国家: 英国
• 起止时间: 2006 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FD014824%2F1
• 关键词: Use; bioactive; polymers; regulate; differentiation

Human embryonic stem (hES) cells, isolated from very early stage embryos, are able to become any cell in the body and have great potential for the treatment of many serious diseases. However there is a practical problem in producing a sufficient number of hES cells to treat human diseases, such as heart disease and cancer. At present hES cells must be grown under specialised conditions as a 2-dimensional (2-D) culture. This severely limits the number of cells that can be obtained and our project will allow the culture of hES cells in 3-dimensions (3-D). To allow you to appreciate the significance of 2-D and 3-D growth of hES cells, imagine how many more tennis balls you could squeeze into your living room compared to those you could only place on the floor. The bigger the volume of the room the more tennis balls you can fit in, irrespective of the area of the floor. Therefore, 3-D growth of hES cells allows us to grow a lot more cells than we can at the present time. However, it's not that easy! If we grow hES cells in 3-D they will either die or turn into other cell types (called differentiation) therefore we need to stop them from differentiating. We will use two methods to stop the hES cells differentiating in 3-D culture. First we will use sugars. These are different to the sugar you put in your coffee since they consist of a long chain containing areas that can regulate biological activities. All the cells in your body naturally contain these sugars and they are very important in maintaining healthy and viable cells. Basically, we will use these sugars to help keep the hES cells feeling well in 3-D culture. The other method we will develop uses oligopeptides. All proteins in your body are made up of amino acids and an oligopeptide is simply a chain of amino acids. Like sugars, peptides can regulate what happens in your body. We will use oligopeptides that make hES cells healthy and allow them to grow in 3-D culture. Sugars and oligopeptides can work well together and we hope that by combining them together we can make the hES cells grow very well in 3-D. In this way we will engineer bioreactors of cells in 3-dimensions that can produce large numbers of hES cells. This will allow us to provide a new technology for mass production of hES cells and then turn them into specific cell types that may help to treat patients with serious diseases.

从非常早期的胚胎中分离出来的人类胚胎干（hES）细胞能够成为体内的任何细胞，并且具有治疗许多严重疾病的巨大潜力。然而，产生足够数量的hES细胞来治疗人类疾病（例如心脏病和癌症）存在实际问题。目前，hES 细胞必须在特殊条件下以二维 (2-D) 培养物的形式生长。这严重限制了可以获得的细胞数量，我们的项目将允许在 3 维 (3-D) 中培养 hES 细胞。为了让您了解 hES 细胞 2-D 和 3-D 生长的重要性，想象一下与只能放在地板上的网球相比，您可以在客厅里多塞多少个网球。房间的体积越大，可以容纳的网球就越多，无论地板面积如何。因此，hES 细胞的 3D 生长使我们能够比目前培养更多的细胞。然而，这并不容易！如果我们以 3D 方式培养 hES 细胞，它们要么死亡，要么转变为其他细胞类型（称为分化），因此我们需要阻止它们分化。我们将使用两种方法来阻止 hES 细胞在 3-D 培养中分化。首先我们将使用糖。它们与您在咖啡中添加的糖不同，因为它们由一条长链组成，其中含有可以调节生物活动的区域。您体内的所有细胞天然都含有这些糖，它们对于维持健康和活力的细胞非常重要。基本上，我们将使用这些糖来帮助 hES 细胞在 3-D 培养中保持良好状态。我们将开发的另一种方法使用寡肽。你体内的所有蛋白质都是由氨基酸组成的，而寡肽只是一条氨基酸链。与糖一样，肽可以调节体内发生的情况。我们将使用寡肽使 hES 细胞保持健康并使其在 3D 培养物中生长。糖和寡肽可以很好地协同工作，我们希望通过将它们结合在一起，我们可以使 hES 细胞在 3D 中生长得很好。通过这种方式，我们将设计出能够产生大量 hES 细胞的 3 维细胞生物反应器。这将使我们能够提供一种大规模生产 hES 细胞的新技术，然后将其转化为可能有助于治疗患有严重疾病的患者的特定细胞类型。

项目成果

Quantitative characterization of cell transduction by HSV-1 amplicons using flow cytometry and real-time PCR.

使用流式细胞术和实时 PCR 对 HSV-1 扩增子的细胞转导进行定量表征。

• DOI: 10.1016/j.jviromet.2009.03.018
• 发表时间: 2009
• 期刊: Journal of virological methods
• 影响因子: 3.1
• 作者: El-Sherbini YM

Enhancement of cell recovery for dissociated human embryonic stem cells after cryopreservation.

冷冻保存后解离的人类胚胎干细胞的细胞恢复增强。

• DOI: 10.1002/btpr.358
• 发表时间: 2010-05
• 期刊: BIOTECHNOLOGY PROGRESS
• 影响因子: 2.9
• 作者: Xu, Xia;Cowley, Sally;Flaim, Christopher J.;James, William;Seymour, Lenard W.;Cui, Zhanfeng
• 通讯作者: Cui, Zhanfeng

The roles of apoptotic pathways in the low recovery rate after cryopreservation of dissociated human embryonic stem cells.

• DOI: 10.1002/btpr.368
• 发表时间: 2010-05
• 期刊: BIOTECHNOLOGY PROGRESS
• 影响因子: 2.9
• 作者: Xu, Xia;Cowley, Sally;Flaim, Christopher J.;James, William;Seymour, Leonard;Cui, Zhanfeng
• 通讯作者: Cui, Zhanfeng