Development of an in vitro musculoskeletal model of human ageing

点击翻译按钮获取中文摘要

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.