Computational Investigations of Mesenchymal Stem Cell Ageing in Mechanobiological Simulations of Tissue Differentiation

Musculoskeletal health is a major determinant of the quality of life for the increasing aged population groups in our society. Improved healthcare is essential to ensure successftil ageing and enhanced musculoskeletal health is pivotal for tackling age-associated diseases such as osteoporosis and osteoarthritis. The primary clinical solutions for treating such diseases are well established for the young population. However, for these therapies to be successftil in elder age groups, for whom tissue repair is mostly needed, it is important to understand the influence of mesenchymal stem cell (MSC) ageing to the tissue differentiation.

A predictive computational model was created using finite element models of single cells implemented with the mechanoregulation theory developed by Prendergast et al. (1997). Two mechanobiological events, the gap tissue formation in reconstructive medicine and the MSC differentiation upon substrate stretching in tissue engineering, were simulated to investigate the effects of MSC ageing on cell-tissue differentiation.

The model was able to capture the sub-cellular changes associated with MSC ageing that is without the reach of other mechanoregulation modelling approaches. Simulation results revealed that changes were evident in the predicted tissue differentiation patterns in response to the application of age-related changes in both events, indicating that MSC ageing affects tissue differentiation and therefore should be considered as a factor when performing MSC-based clinical applications.

Most importantly, it was also demonstrated that the presented cell-based mechanoregulation modelling approach is capable of corroborating mechanoregulation theories with basic in vitro cell experiments. It could also potentially be used to calibrate well-established mechanoregulation algorithms in the ftiture, to give reliable individual-based, and ultimately, patient-specific predictions prior to operation. Mechanoregulation simulation, or computational mechanobiology as a whole, would then realise its true clinical potential.

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Year

Entry

1991

Ingber D. Integrins as mechanochemical transducers. Curr Opin Cell Biol. October 1991;3(5):841-848.

2003

Silver FH, Freeman JW, Seehra GP. Collagen self-assembly and the development of tendon mechanical properties. J Biomech. October 2003;36(10):1529-1553.

2000

Guilak F, Tedrow JR, Burgkart R. Viscoelastic properties of the cell nucleus. Biochem Biophys Res Commun. March 24, 2000;269(3):781-786.

2000

Grodzinsky AJ, Levenston ME, Jin M, Frank EH. Cartilage tissue remodeling in response to mechanical forces. Annu Rev Biomed Eng. 2000;2:691-713.

2002

Lacroix D, Prendergast PJ. A mechano-regulation model for tissue differentiation during fracture healing: analysis of gap size and loading. J Biomech. September 2002;35(9):1163-1171.