Adult stem cell biology and musculoskeletal tissue engineering: research projects

Regenerative Medicine - Adult stem cell biology and musculoskeletal tissue engineering - Current

Effect of mesenchymal stem cell ageing on the efficacy of musculoskeletal tissue engineering approaches

Abstract

Ageing is associated with an increased number of diseases affecting the skeletal system, such as osteoarthritis (OA), osteoporosis (OP)  and intervertebral disc (IVD) degeneration (one of the leading causes of lower back pain), for which at present there are no successful clinical therapies. Therefore as the population ages, so this translates to increased burdens on the healthcare systems, as well as pain and suffering for an ever increasing proportion of society.

Recently, an increasing range of tissue engineering and regenerative medicine therapies have been proposed for age-related diseases, many using adult autologous MSCs derived from either bone marrow (BM-MSCs) or adipose tissue (AD-MSCs). However, studies have suggested that BM-MSCs from donors with age-related diseases such as osteoporosis have an impaired differentiation capability and shortened lifespan in vitro. Recent studies also suggest that BM-MSCs may undergo a process of ageing (cellular senescence) in vivo which is a similar process to that described during extended culture in vitro. If so, this would make them unsuitable for tissue engineering therapies and while AD-MSCs may present a viable alternative, little is currently known about age-related or disease-related cellular senescence in these cells either in vivo or in vitro. Therefore this application aims to investigate a number of unanswered questions regarding stem cell senescence and their suitability for regenerative medicine. In particular, it will aim to address the following questions:

  1. Do BM-MSCs or AD-MSCs from aged individuals or individuals with musculoskeletal disease show evidence or markers of cellular senescence?
  2. Do these factors affect MSC differentiation or functionality on biomaterials for regenerative medicine applications and do BM-MSCs and AD-MSCs behave differently?
  3. For regenerative medicine applications where expansion is required, does replicative senescence in vitro occur more rapidly in BM-MSCs or AD-MSCs from aged individuals or individuals with musculoskeletal disease and does this affect their subsequent behaviour on biomaterials for musculoskeletal regenerative medicine applications?

Duration of the project

36 months

Funding body

Furlong Research Charitable Foundation

Members of the project

Dr Stephen RichardsonPrincipal investigator
Professor Judith HoylandCo-investigator
Miss Kimberley SwintonPhD student