UKRMP Hub: The Engineered Cell Environment.

UKRMP 中心：工程细胞环境。

• 批准号: MR/R015635/1
• 负责人: Stuart Forbes
• 金额: $ 537.51万
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FR015635%2F1
• 关键词: UKRMP; Hub; Engineered; Cell; Environment.

Stem cells have great potential in medicine as they can grow into many different cell types in the body. Our aim is to create a research network of scientists and clinicians working towards understanding how stem cells behave within their normal tissue environment. The environment or "Niche" within the body that surrounds stem cells has a profound effect on the behaviour of stem cells and whether they can repair damaged organs. By understanding how the Niche influences stem cells in tissues we aim to use this knowledge to develop future treatments for serious untreatable diseases.To promote "healthy regeneration" in tissues and organs, we will use 2 main strategies: (1) test drugs and small synthetic molecules in experimental models of organ injury. We hope to influence the behaviour of the stem cells within their Niche environment by adding drugs. (2) Another way of treating damaged tissue and organs is to transplant stem cells or cells from stem cells into the damaged organ - this kind of treatment is known as a cell therapy and an example of this used today to treat patients is bone marrow transplantation. Whilst this treatment is successful for many diseases, in some cases this treatment does not work and the cells do not grow well. Our network wants to understand why the Niche environment does not always allow cells to grow well. We hope to develop novel treatments using cell transplantation to promote healthy regeneration of tissue and organs.We aim to develop treatments for patients who are currently suffering from untreatable diseases affecting the (a) liver, (b) joints and the (c) lungs. (a) Liver disease is the 5th most common cause of death in the UK. The current treatment for patients with end-stage cirrhosis and acute liver failure is a liver transplant, however organ availability cannot meet demand and many patients die waiting for an organ. Those who do undergo transplantation require lifelong immunosuppression with concomitant risks of infection, cancer, renal and cardiovascular disease. Thus, there is a clear imperative to identify alternatives treatments. One of our research themes will investigate healthy regeneration of the liver using drugs or cell therapies. (b) Another research theme from our Hub investigates new treatments for Osteoarthritis (OA) which is one of the fastest most rapidly increasing major health conditions, with over 8 million people affected in the UK alone. Whilst end-stage disease is suited to joint replacement, there is an urgent need to address earlier disease stages with repair and regenerative strategies. (c) We are also investigating regeneration of the lung; chronic lung disease is responsible for 6 million inpatient bed days a year in the UK. There is a clear unmet need for this research to be carried out.We will bring together scientists with the different kinds of expertise that we think are required to tackle these scientific and medical challenges. By linking these experts with doctors working in these clinical areas and helping them to collaborate together we hope to make more rapid progress in the development of new treatments for these chronic diseases.

干细胞在医学上具有巨大的潜力，因为它们可以在体内生长成许多不同的细胞类型。我们的目标是建立一个科学家和临床医生的研究网络，致力于了解干细胞在正常组织环境中的行为。身体内围绕干细胞的环境或“生态位”对干细胞的行为以及它们是否可以修复受损器官有着深远的影响。通过了解生态位如何影响组织中的干细胞，我们的目标是利用这些知识来开发未来治疗严重无法治愈的疾病的方法。为了促进组织和器官的“健康再生”，我们将使用两种主要策略：（1）在器官损伤的实验模型中测试药物和小合成分子。我们希望通过添加药物来影响干细胞在其生态位环境中的行为。(2)治疗受损组织和器官的另一种方法是将干细胞或干细胞中的细胞移植到受损器官中-这种治疗被称为细胞疗法，今天用于治疗患者的一个例子是骨髓移植。虽然这种治疗对许多疾病都是成功的，但在某些情况下，这种治疗不起作用，细胞生长不好。我们的网络想了解为什么利基环境并不总是让细胞生长良好。我们希望通过细胞移植开发新的治疗方法，以促进组织和器官的健康再生。我们的目标是为目前患有无法治愈的疾病的患者开发治疗方法，这些疾病影响（a）肝脏，（B）关节和（c）肺部。(a)肝病是英国第五大常见的死亡原因。目前对终末期肝硬化和急性肝功能衰竭患者的治疗是肝移植，但器官供应无法满足需求，许多患者因等待器官而死亡。那些接受移植的人需要终身免疫抑制，伴随着感染、癌症、肾脏和心血管疾病的风险。因此，确定替代治疗方法显然势在必行。我们的研究主题之一将研究使用药物或细胞疗法的肝脏健康再生。(b)我们中心的另一个研究主题是研究骨关节炎（OA）的新疗法，这是增长最快的主要健康状况之一，仅在英国就有超过800万人受到影响。虽然终末期疾病适合关节置换，但迫切需要通过修复和再生策略来解决早期疾病阶段。(c)我们还在研究肺的再生;慢性肺病在英国每年造成600万住院日。这项研究显然有未满足的需求，我们将召集具有我们认为应对这些科学和医学挑战所需的不同专业知识的科学家。通过将这些专家与在这些临床领域工作的医生联系起来，并帮助他们共同合作，我们希望在开发这些慢性疾病的新疗法方面取得更快的进展。

项目成果

Human osteoblasts obtained from distinct periarticular sites demonstrate differences in biological function in vitro.

从不同关节周围部位获得的人成骨细胞在体外表现出生物学功能的差异。

• DOI: 10.17863/cam.76398
• 发表时间: 2021
• 作者: Ali E

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

Early human lung immune cell development and its role in epithelial cell fate

早期人肺免疫细胞发育及其在上皮细胞命运中的作用

• DOI: 10.1101/2022.12.13.519713
• 发表时间: 2022
• 作者: Barnes J

Rat liver ECM incorporated into electrospun polycaprolactone scaffolds as a platform for hepatocyte culture.

• DOI: 10.1002/jbm.b.35115
• 发表时间: 2022-12
• 期刊: JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS
• 影响因子: 3.4
• 作者: Bate, Thomas S. R.;Shanahan, William;Casillo, Joseph P.;Grant, Rhiannon;Forbes, Stuart J.;Callanan, Anthony
• 通讯作者: Callanan, Anthony

Response differences of HepG2 and Primary Mouse Hepatocytes to morphological changes in electrospun PCL scaffolds.

HEPG2和原代小鼠肝细胞对电纺PCL支架的形态变化的反应差异。

• DOI: 10.1038/s41598-021-81761-z
• 发表时间: 2021-02-04
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Bate TSR;Gadd VL;Forbes SJ;Callanan A
• 通讯作者: Callanan A