权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Combining stem cell science and tissue engineering to study the development and repair of human skeletal tissue

结合干细胞科学和组织工程学研究人体骨骼组织的发育和修复

基本信息

批准号：
BB/G010579/1
负责人：
Richard Oreffo
金额：
$ 203.97万
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：
2009
资助国家：
英国
起止时间：
2009 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FG010579%2F1
关键词：
Combining stem cell science tissue

项目摘要

With an ever increasing ageing population, strategies that allow the simple repair and enhancement of bone tissue, lost due to diseases such as osteoporosis and osteoarthritis or with ageing or after an accident, are urgently needed. Whilst there are a number of surgical techniques that can be used to repair bone and to aid fracture healing, there is a great need for the development of alternative bone and cartilage repair and regeneration strategies. To try and solve the lack of bone a patient may have at one site, the surgeon can try and harvest and use existing bone from another site (known as autogenous bone) in the patient although, naturally, the amounts available to use are limited. Other options include the use of donor bone from a different individual (known as allogeneic bone). However donor bone carries risks of rejection and infection. Tissue engineering aims to make tissues and organs - including bone tissue - using stem and precursor cells, scaffolds upon which the cells can grow and be guided, and necessary mechanical cues to create bone tissue in the laboratory for transplantation to replace damaged or diseased tissues. Within all our bone marrow are stem cells (called skeletal or mesenchymal stem cells), which can be isolated using selective markers and which can be grown up to give lots of cells, while retaining their ability to form a variety of tissues like bone and fat. Similarly we have expertise in the ability to create structures (scaffolds) for the cells to grow on and these scaffolds can be tailored to release select growth factors and proteins needed to guide and tell the stem cells to make bone and cartilage. In addition, we know that mechanical cues are very important in stimulating new bone growth (for example we know excessive bed rest or weightlessness leads to loss of bone). Thus the application of stem cells, select scaffolds and the use of signalling cues to generate new bone tissue is currently one of the most exciting and promising areas for disease treatment and bone repair. We propose as well as combining these key ingredients, that, critically, a new way of thinking as to how scientists currently try to create skeletal tissue is urgently needed if we are to meet the challenges of new skeletal formation for an increasing ageing population. We propose that it is vital to understand bone development and formation and that if we can harness the information of how bone develops and if we can understand bone biology, this will set the foundation and inform us how to repair and make new skeletal tissue. Thus, we propose an ambitious programme of research to significantly advance the state-of-the-art in developmental biology, stem cells, materials chemistry, mechanical signalling and loading and translational medicine to generate new models of skeletal development that can be used to inform skeletal repair strategies for clinical use in bone repair and regeneration. To achieve our goal we will use a multidisciplinary strategy that brings together stem cell biologists, developmental biologists, materials scientists, mechanobiologists and clinicians with an ability to draw lessons from skeletal developmental biology to inform our tissue engineering strategy for skeletal formation and repair.

随着人口老龄化的不断增加，迫切需要允许简单修复和增强由于骨质疏松症和骨关节炎等疾病或衰老或事故后丢失的骨组织的策略。虽然有许多手术技术可用于修复骨和帮助骨折愈合，但非常需要开发替代性骨和软骨修复和再生策略。为了尝试解决患者在一个部位可能存在的骨缺乏问题，外科医生可以尝试从患者的另一个部位（称为自体骨）采集和使用现有的骨，尽管自然地，可供使用的量是有限的。其他选择包括使用来自不同个体的供体骨（称为同种异体骨）。然而，供体骨具有排斥和感染的风险。组织工程旨在利用干细胞和前体细胞、细胞可以生长和被引导的支架以及必要的机械线索来制造组织和器官-包括骨组织-以在实验室中创建骨组织用于移植以替换受损或患病的组织。在我们所有的骨髓中都有干细胞（称为骨骼或间充质干细胞），它们可以使用选择性标记分离出来，并且可以生长为大量细胞，同时保留它们形成各种组织如骨骼和脂肪的能力。同样，我们有能力创造细胞生长的结构（支架），这些支架可以被定制以释放选择的生长因子和蛋白质，这些生长因子和蛋白质需要引导和告诉干细胞制造骨骼和软骨。此外，我们知道机械刺激在刺激新骨生长方面非常重要（例如，我们知道过度卧床休息或失重会导致骨丢失）。因此，应用干细胞，选择支架和使用信号线索来产生新的骨组织是目前疾病治疗和骨修复最令人兴奋和最有前途的领域之一。我们建议，以及结合这些关键成分，即，至关重要的是，一种新的思维方式，科学家目前如何试图创造骨骼组织是迫切需要的，如果我们要满足新的骨骼形成的挑战，为日益老龄化的人口。我们认为，了解骨骼发育和形成至关重要，如果我们能够利用骨骼发育的信息，如果我们能够了解骨骼生物学，这将为我们提供基础，并告知我们如何修复和制造新的骨骼组织。因此，我们提出了一个雄心勃勃的研究计划，以显着推进最先进的发育生物学，干细胞，材料化学，机械信号和负载和转化医学，以产生新的骨骼发育模型，可用于通知骨骼修复策略，用于骨修复和再生的临床应用。为了实现我们的目标，我们将采用多学科策略，将干细胞生物学家，发育生物学家，材料科学家，机械生物学家和临床医生聚集在一起，能够从骨骼发育生物学中吸取教训，为我们的骨骼形成和修复组织工程策略提供信息。

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）

Osteogenic lineage restriction by osteoprogenitors cultured on nanometric grooved surfaces: the role of focal adhesion maturation.

DOI：
10.1016/j.actbio.2013.11.008
发表时间：
2014-02
期刊：
ACTA BIOMATERIALIA
影响因子：
9.7
作者：
Cassidy, John W.;Roberts, Jemma N.;Smith, Carol-Anne;Robertson, Mary;White, Kate;Biggs, Manus J.;Oreffo, Richard O. C.;Dalby, Matthew J.
通讯作者：
Dalby, Matthew J.

Synthesis of scaffold-free, three dimensional, osteogenic constructs following culture of skeletal osteoprogenitor cells on glass surfaces.

DOI：
10.1016/j.bonr.2021.101143
发表时间：
2021-12
期刊：
Bone reports
影响因子：
2.5
作者：
Alghfeli L;Parambath D;Manzoor S;Roach HI;Oreffo ROC;El-Serafi AT
通讯作者：
El-Serafi AT

A tissue engineering strategy for the treatment of avascular necrosis of the femoral head.

DOI：
10.1016/j.surge.2013.02.008
发表时间：
2013-12
期刊：
SURGEON-JOURNAL OF THE ROYAL COLLEGES OF SURGEONS OF EDINBURGH AND IRELAND
影响因子：
2.5
作者：
Aarvold, A.;Smith, J. O.;Tayton, E. R.;Jones, A. M. H.;Dawson, J. I.;Lanham, S.;Briscoe, A.;Dunlop, D. G.;Oreffo, R. O. C.
通讯作者：
Oreffo, R. O. C.

Bone Tissue Engineering.