Development of an in vitro musculoskeletal model of human ageing

人类衰老体外肌肉骨骼模型的开发

• 批准号: 2590408
• 金额: --
• 依托单位: University of Sheffield
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2590408
• 关键词: Development; vitro; musculoskeletal; model; human

Globally, musculoskeletal (MSK) conditions are the leading contributor to disability and are commonly linked with depression and negative impacts on quality of life. MSK conditions have a significant economic impact worldwide and their prevalence is predicted to rise with an increasingly ageing global population.Currently drug treatments for MSK conditions are screened using monocultures or, at best, co-cultures of cells growing in monolayers in vitro. However, the cell-cell and cell-matrix interactions within the tissues together with the differing mechanical and structural properties of these tissues at the interface between muscle, bone and cartilage mean that monolayer models fail to capture these interactions. MSK ageing also induces extracellular matrix changes but simple 2D monocultures are incapable of recapitulating these changes in any meaningful way. As a consequence, researchers often turn to animal models. However, important differences in size, anatomy and biomechanics limit their relevance and hinder successful outcomes in the MSK drug development. Attempts to develop 3D models have been described in the literature, but success in this area is limited with many versions incorporating the cells from only one tissue type and therefore omitting the interactions between cell types. There is therefore an unmet need for a reliable, biologically relevant in vitro model of the MSK interface that can reduce and replace animal models, reflect the ageing process and thereby accelerate the development of MSK treatments.

在全球范围内，肌肉骨骼（MSK）疾病是导致残疾的主要因素，通常与抑郁症和对生活质量的负面影响有关。MSK条件有显着的经济影响世界各地和他们的患病率预计将上升与日益老龄化的全球population.Currently MSK条件的药物治疗筛选使用单一培养或，最好的，在体外单层细胞生长的共培养物。然而，组织内的细胞-细胞和细胞-基质相互作用以及这些组织在肌肉、骨和软骨之间的界面处的不同机械和结构特性意味着单层模型未能捕获这些相互作用。MSK老化也会诱导细胞外基质的变化，但简单的2D单一培养物无法以任何有意义的方式重现这些变化。因此，研究人员经常求助于动物模型。然而，尺寸、解剖结构和生物力学方面的重要差异限制了它们的相关性，并阻碍了MSK药物开发的成功结果。在文献中已经描述了开发3D模型的尝试，但是在该领域的成功受到限制，许多版本仅包含来自一种组织类型的细胞，因此省略了细胞类型之间的相互作用。因此，存在对MSK界面的可靠的、生物学相关的体外模型的未满足的需求，该模型可以减少和替代动物模型，反映老化过程，从而加速MSK治疗的发展。