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The use of microRNAs and nanotopography to modulate skeletal stem cell fate and function

使用 microRNA 和纳米形貌来调节骨骼干细胞的命运和功能

基本信息

批准号：
BB/L021072/1
负责人：
Richard Oreffo
金额：
$ 49.56万
依托单位：
University of Southampton
依托单位国家：
英国
项目类别：
Research Grant
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=BB%2FL021072%2F1
关键词：
use microRNAs nanotopography modulate skeletal

项目摘要

Medical advances have led to a welcome increase in life expectancy. However, increased aging populations pose new challenges and emphasize the need for novel approaches to aid and repair tissue lost through damage or disease. By 2020 approximately 20% of the UK population will be over 65 and the numbers of hip fractures worldwide will increase from 1.7 million in 1990 to 6.3 million in 2050. Thus, there is now an urgent need to understand how to maintain stem cells and then how to direct them into cell types we want such as bone and cartilage to enhance bone repair and improve quality of life for the patient. However, despite intensive research interest there is limited information on how to reproducibly maintain the bone stem cells (known as skeletal or mesenchymal stem cells); or indeed how to tell a bone stem cell to make bone or cartilage. Fortunately, human bone marrow contains these special skeletal stem cells. These stem cells can easily be obtained from these tissues and have the potential to form a variety of tissue types such as cartilage, bone, muscle, tendon, ligament and fat (for this reason, skeletal stem cells are currently one of the most exciting and promising areas for tissue engineering and reparative medicine and in the future this will allow stem cell-based therapies to be developed to treat or cure diseases).We are particularly interested in understanding how to maintain stem cells and to switch (differentiate) these bone stem cells to new bone and cartilage fat for regenerative medicine. For this approach to be successful, it is crucial to understand the way in which these skeletal stem cells change to become mature bone or retain their stem characteristics. Unlocking the molecular signals is the key to developing understanding and being able to undertake these studies in the absence of chemical cues is critical (to avoid confusing signals due to the chemicals used); we have powerful early data showing small nucleotides called microRNAs are key.MicroRNAs (miRNAs), are very small (only 18-25 nucleotides) non-protein-coding single-stranded RNAs that have the ability to regulate gene transcription. They have important and varied roles in many biological and disease related processes. There is new and exciting data to suggest i) a number of miRNAs are specifically expressed in stem cells, ii) they can control stem cell self-renewal, and, iii) they can control the ability of stem cells to form different tissue types. In addition we have data on nanotopographical surfaces (surfaces that can change or maintain our stem cells without any chemical cues) indicating the key role of microRNAs in keeping or changing bone stem cells. We will look at how these microRNAs affect cell behaviour and cytoskeleton (proteins involved in cell adhesion, spreading, metabolism and signalling), cell growth and differentiation.The results of this proposed project will open the way to modulate bone stem cells and thus drive the stems cells towards the desired cell type and provides exciting healthcare opportunities that will benefit many.

医学的进步使人们的预期寿命得到了可喜的延长。然而，人口老龄化的增加带来了新的挑战，并强调需要新的方法来帮助和修复因损伤或疾病而丢失的组织。到2020年，大约20%的英国人口将超过65岁，全球髋部骨折的数量将从1990年的170万增加到2050年的630万。因此，现在迫切需要了解如何维持干细胞，然后如何将它们引导成我们想要的细胞类型，如骨和软骨，以增强骨修复并提高患者的生活质量。然而，尽管研究兴趣浓厚，但关于如何可再生地维持骨干细胞（称为骨骼或间充质干细胞）的信息有限；或者确切地说，如何告诉骨干细胞生成骨或软骨。幸运的是，人类骨髓中含有这些特殊的骨骼干细胞。这些干细胞可以很容易地从这些组织中获得，并且有可能形成各种组织类型，如软骨、骨骼、肌肉、肌腱、韧带和脂肪（因此，骨骼干细胞是目前组织工程和修复医学中最令人兴奋和最有前途的领域之一，未来这将允许开发基于干细胞的疗法来治疗或治愈疾病）。我们特别感兴趣的是了解如何维持干细胞，并将这些骨干细胞转换（分化）为新的骨和软骨脂肪，用于再生医学。为了使这种方法取得成功，了解这些骨骼干细胞转变为成熟骨骼或保持其干细胞特征的方式至关重要。解开分子信号是发展理解的关键，能够在没有化学线索的情况下进行这些研究是至关重要的（避免由于使用的化学物质而导致信号混淆）；我们有强大的早期数据表明，被称为microrna的小核苷酸是关键。MicroRNAs （miRNAs）是非常小的（只有18-25个核苷酸）非蛋白质编码单链rna，具有调节基因转录的能力。它们在许多生物和疾病相关过程中发挥着重要而多样的作用。新的令人兴奋的数据表明，1)许多mirna在干细胞中特异性表达，2)它们可以控制干细胞的自我更新，3)它们可以控制干细胞形成不同组织类型的能力。此外，我们有纳米形貌表面（可以在没有任何化学线索的情况下改变或维持干细胞的表面）的数据，表明microrna在保持或改变骨干细胞方面的关键作用。我们将研究这些microrna如何影响细胞行为和细胞骨架（参与细胞粘附、扩散、代谢和信号传导的蛋白质）、细胞生长和分化。这个项目的结果将为调节骨干细胞开辟道路，从而推动干细胞向所需的细胞类型发展，并提供令人兴奋的医疗保健机会，这将使许多人受益。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Quantitative temporal interrogation in 3D of bioengineered human cartilage using multimodal label-free imaging.

DOI：
10.1039/c8ib00050f
发表时间：
2018-10
期刊：
Integrative biology : quantitative biosciences from nano to macro
影响因子：
0
作者：
Catarina Costa Moura;S. Lanham;Tual Monfort;K. Bourdakos;Rahul S. Tare;R. Oreffo;S. Mahajan
通讯作者：
Catarina Costa Moura;S. Lanham;Tual Monfort;K. Bourdakos;Rahul S. Tare;R. Oreffo;S. Mahajan

Harnessing Nanotopography to Enhance Osseointegration of Clinical Orthopedic Titanium Implants-An in Vitro and in Vivo Analysis.