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Harnessing clay nano-particles for stem-cell driven tissue regeneration

利用粘土纳米颗粒进行干细胞驱动的组织再生

基本信息

批准号：
EP/L010259/1
负责人：
Jonathan Dawson
金额：
$ 133.67万
依托单位：
University of Southampton
依托单位国家：
英国
项目类别：
Fellowship
财政年份：
2014
资助国家：
英国
起止时间：
2014 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=EP%2FL010259%2F1
关键词：
Harnessing clay nano particles stem

项目摘要

Gels made from clay could provide an environment able to stimulate stem-cells due to their ability to bind biological molecules. That molecules stick to clay has been known by scientists since the 1960s. Doctors observed that absorption into the blood stream of certain drugs was severely reduced when patients were also receiving clay-based antacid or anti-diarrhoeal treatments. This curious phenomenon was realized to be due to binding of the drugs by clay particles. This interaction is now routinely harnessed in the design of tablets to carefully control the release and action of a drug. Dr Dawson now proposes to use this property of clay to create micro-environments that could stimulate stem cells to regenerate damaged tissues such as bone, skin, heart, spinal cord, liver, pancreas and cornea.The rich electrostatic properties of nano (1 millionth of a millimetre) -scale clay particles which mediate these interactions could allow two hurdles facing the development of stem-cell based regenerative therapies to be overcome simultaneously.The first challenge - to deliver and hold stem cells at the right location in the body - is met by the ability of clays to self-organise into gels via the electrostatic interactions of the particles with each other. Cells mixed with a low concentration (less than 4%) of clay particles can be injected into the body and held in the right place by the gel, eliminating, in many situations, the need for surgery. Clay particles can also interact with large structural molecules (polymers) which are frequently used in the development of materials (or 'scaffolds'), designed to host stem cells. These interactions can greatly improve the strength of such structures and could be applied to preserve their stability at the site of injury until regeneration is complete.While several gels and scaffold materials have been designed to deliver and hold stem cells at the site of regeneration, the ability of clay nanoparticles to overcome a second critical hurdle facing stem-cell therapy is what makes them especially exciting. Essential to directing the activity of stem-cells is the carefully controlled provision of key biological signalling molecules. However, the open structures of conventional scaffolds or gels, while essential for the diffusion of nutrients to the cells, means their ability to hold the signalling molecules in the same location as the cells is limited. The ability of clay nano-particles to bind biological molecules presents a unique opportunity to create local environments at a site of injury or disease that can stimulate and control stem-cell driven repair. Dr Dawson's early studies investigated the ability of clay gels to stimulate the growth of new blood vessels by incorporating a key molecular signal that stimulates this process, vascular endothelial growth factor (VEGF). In a manner reminiscent of the observations made in the 60s, Dr Dawson and colleagues observed that adding a drop of clay gel to a solution containing VEGF caused, after a few hours, the disappearance of VEGF from the solution as it became bound to the gel. When placed in an experimental injury model, the gel-bound VEGF stimulated a cluster of new blood vessels to form. These exciting results indicate the potential of clay nanoparticles to create tailor-made micro-environments to foster stem cell regeneration. Dr Dawson is developing this approach as a means of first exploring the biological signals necessary to successfully control stem cell behaviour for regeneration and then, using the same approach, to provide stem cells with these signals to stimulate regeneration in the body.The project will seek to test this approach to regenerate bone lost to cancer or hip replacement failure. If successful the same technology may be applied to harness stem cells for the treatment of a whole host of different scenarios, from burn victims to those suffering with diabetes or Parkinson's.

由粘土制成的凝胶可以提供一个能够刺激干细胞的环境，因为它们具有结合生物分子的能力。自20世纪60年代以来，科学家们就知道分子会粘在粘土上。医生们观察到，当病人同时接受粘土制酸剂或抗腹泻治疗时，某些药物在血液中的吸收会严重减少。这种奇怪的现象被认为是由于粘土颗粒对药物的结合。现在，这种相互作用在片剂设计中被常规利用，以仔细控制药物的释放和作用。道森博士现在提出利用粘土的这种特性来创造微环境，刺激干细胞再生受损组织，如骨骼、皮肤、心脏、脊髓、肝脏，胰腺和角膜。纳米材料丰富的静电特性（百万分之一毫米）规模的粘土颗粒，调解这些相互作用可能会允许两个障碍面临的发展，茎-第一个挑战--将干细胞输送并保持在体内的正确位置--是通过粘土颗粒之间的静电相互作用自组织成凝胶的能力来解决的。与低浓度（小于4%）粘土颗粒混合的细胞可以被注射到体内，并通过凝胶保持在正确的位置，在许多情况下，消除了手术的需要。粘土颗粒也可以与大的结构分子（聚合物）相互作用，这些分子经常用于开发设计用于宿主干细胞的材料（或“支架”）。这些相互作用可以极大地提高这种结构的强度，并可用于保持其在损伤部位的稳定性，直到再生完成。虽然已经设计了几种凝胶和支架材料来将干细胞输送和保持在再生部位，但粘土纳米颗粒克服干细胞治疗面临的第二个关键障碍的能力是使它们特别令人兴奋的。指导干细胞活动的关键是仔细控制关键生物信号分子的供应。然而，传统支架或凝胶的开放结构虽然对于营养物质向细胞的扩散至关重要，但意味着它们将信号分子保持在与细胞相同位置的能力有限。粘土纳米颗粒结合生物分子的能力提供了一个独特的机会，可以在损伤或疾病部位创造局部环境，刺激和控制干细胞驱动的修复。Dawson博士的早期研究调查了粘土凝胶刺激新血管生长的能力，通过结合刺激这一过程的关键分子信号，血管内皮生长因子（VEGF）。Dawson博士和他的同事们以一种让人想起60年代所做的观察的方式观察到，在含有VEGF的溶液中加入一滴粘土凝胶，几个小时后，当它与凝胶结合时，溶液中的VEGF就会消失。当置于实验损伤模型中时，凝胶结合的VEGF刺激了一簇新血管的形成。这些令人兴奋的结果表明，粘土纳米颗粒有潜力创造量身定制的微环境，以促进干细胞再生。道森博士正在开发这种方法，首先探索成功控制干细胞再生行为所必需的生物信号，然后使用同样的方法为干细胞提供这些信号，以刺激体内再生。该项目将试图测试这种方法，以再生因癌症或髋关节置换术失败而丢失的骨骼。如果成功的话，同样的技术可以应用于利用干细胞治疗各种不同的情况，从烧伤患者到糖尿病或帕金森病患者。