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Identifying the skeletal stem cell for regeneration: harnessing smart nanoparticles and single cell DropSeq molecular profiling platforms

识别用于再生的骨骼干细胞：利用智能纳米粒子和单细胞 DropSeq 分子分析平台

基本信息

批准号：
BB/P017711/1
负责人：
Richard Oreffo
金额：
$ 86.08万
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：
2017
资助国家：
英国
起止时间：
2017 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FP017711%2F1
关键词：
Identifying skeletal stem cell regeneration

项目摘要

We are now living much longer than we used to. These are exciting times in medical research and indeed, medical advances have led to a welcome increase in life expectancy. However, an unfortunate consequence of this is that as we reach later life the chances that we can become ill or injured increase dramatically. One big problem that elderly people face is illness and injury associated with the bones and joints. Diseases like osteoporosis and arthritis cause pain, cause bone fractures and lead to immobility and distress to tens of thousands of people each year, costing the taxpayer tens of millions of pounds (in the UK there are some 150,000 osteoporosis-associated wrist, spine and hip fractures, with an estimated healthcare cost of £1.7 billion per annum). So new treatments that enable the skeleton to heal better are urgently required. Cell-based therapies are currently some of the most exciting and promising areas for bone disease treatment and reparative medicine. However, despite intensive research interest there are currently no reliable methods to isolate (or enrich sufficiently) the rare bone stem cells (known as skeletal stem cells) needed for these strategies. Thus, it is critical that new technologies be generated to enable the robust isolation of bone stem cells from patients (from their bone marrow) for clinical use. We propose that new approaches, which combine stem cell biology with the latest approaches to identify and cells together with innovative statistical methods will allow us to enrich and isolate the bone stem cell. In this unique programme of work we will be able, for the first time, to use very small (nanoscale) probes to further refine our cell selection and identification strategy. In particular, we will combine a novel single cell identification procedure (which produces a "barcode" for each cell) with unique cell sorting devices to allow us to isolate bone stem cells. We will combine the unique bar codes (derived from the molecular (RNA) machinery) in the individual cells in combination with the smart nano-probes to allow us to tag cells that will separate and examine if they are stem cells and their ability to make bone and cartilage. Through this unique approach we will enrich for bone stem cells that we will characterise and examine if they are stem cells and test their ability to make bone and cartilage.This exciting programme of research offers the ability to isolate the bone stem cell and provide substantially enriched, and potentially pure populations of bone stem cells. This will advance considerably our understanding of bone stem cell basic biology and offer significant therapeutic impact for bone repair and the treatment of bone disorders in our ageing population.

我们现在的寿命比以前长得多。这是医学研究的激动人心的时代，事实上，医学进步带来了预期寿命的可喜增长。然而，这样做的一个不幸的后果是，随着我们晚年的生活，我们生病或受伤的机会急剧增加。老年人面临的一大问题是与骨骼和关节相关的疾病和损伤。骨质疏松症和关节炎等疾病每年都会导致数万人疼痛、骨折、行动不便和痛苦，从而使纳税人损失数千万英镑（在英国，约有 15 万例与骨质疏松症相关的手腕、脊柱和髋部骨折，每年的医疗费用估计为 17 亿英镑）。因此，迫切需要新的治疗方法，使骨骼能够更好地愈合。基于细胞的疗法是目前骨病治疗和修复医学中最令人兴奋和最有前途的领域之一。然而，尽管研究兴趣广泛，但目前还没有可靠的方法来分离（或充分富集）这些策略所需的稀有骨干细胞（称为骨骼干细胞）。因此，至关重要的是开发新技术，以实现从患者（从他们的骨髓）中强有力地分离骨干细胞以供临床使用。我们提出，将干细胞生物学与最新的细胞识别方法和创新的统计方法相结合的新方法将使我们能够富集和分离骨干细胞。在这个独特的工作计划中，我们将首次能够使用非常小的（纳米级）探针来进一步完善我们的细胞选择和识别策略。特别是，我们将把一种新颖的单细胞识别程序（为每个细胞生成一个“条形码”）与独特的细胞分选设备结合起来，使我们能够分离骨干细胞。我们将单个细胞中独特的条形码（源自分子（RNA）机制）与智能纳米探针结合起来，使我们能够标记细胞，分离并检查它们是否是干细胞及其制造骨骼和软骨的能力。通过这种独特的方法，我们将富集骨干细胞，我们将表征和检查它们是否是干细胞，并测试它们制造骨骼和软骨的能力。这项令人兴奋的研究计划提供了分离骨干细胞并提供充分富集且可能纯的骨干细胞群的能力。这将大大增进我们对骨干细胞基础生物学的理解，并对骨修复和老年人群骨疾病的治疗产生重大的治疗影响。

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）

Cell-controlled dynamic surfaces for skeletal stem cell growth and differentiation.

DOI：
10.1038/s41598-022-12057-z
发表时间：
2022-05-17
期刊：
SCIENTIFIC REPORTS
影响因子：
4.6
作者：
Anderson, Hilary J.;Sahoo, Jugal Kishore;Wells, Julia;van Nuffel, Sebastiaan;Dhowre, Hala S.;Oreffo, Richard O. C.;Zelzer, Mischa;Ulijn, Rein V.;Dalby, Matthew J.
通讯作者：
Dalby, Matthew J.

DNA Gold Nanoparticle Motors Demonstrate Processive Motion with Bursts of Speed Up to 50 nm Per Second

DOI：
10.1021/acsnano.0c10658
发表时间：
2021-05-06
期刊：
ACS NANO
影响因子：
17.1
作者：
Bazrafshan, Alisina;Kyriazi, Maria-Eleni;Salaita, Khalid
通讯作者：
Salaita, Khalid

Modelling skeletal pain harnessing tissue engineering.

DOI：
10.1007/s44164-022-00028-7
发表时间：
2022
期刊：
In vitro models
影响因子：
0
作者：
通讯作者：

Chemically modified nucleic acids and DNA intercalators as tools for nanoparticle assembly.

DOI：
10.1039/d1cs00632k
发表时间：
2021-11-29
期刊：
Chemical Society reviews
影响因子：
46.2
作者：
De Fazio AF;Misatziou D;Baker YR;Muskens OL;Brown T;Kanaras AG
通讯作者：
Kanaras AG

A blueprint for translational regenerative medicine.

DOI：
10.1126/scitranslmed.aaz2253
发表时间：
2020-12-02
期刊：
Science translational medicine
影响因子：
17.1
作者：
Armstrong JPK;Keane TJ;Roques AC;Patrick PS;Mooney CM;Kuan WL;Pisupati V;Oreffo ROC;Stuckey DJ;Watt FM;Forbes SJ;Barker RA;Stevens MM
通讯作者：
Stevens MM