OVERVIEW: The core objective of the PhD is to develop a new pneumatic (hydrostatic) pressure bioreactor for manufacturing mesenchymal stem cells. You will develop our hydrostatic (pulsed pressure) generator module to create a ‘cell factory’ bioreactor which improves both the growth rate and ultimate therapeutic effectiveness of cultured stem cells. This project would suit either a biological sciences or electronic/mechanical engineering student with a strong interest in cross-cutting interdisciplinary research, and full training will be provided.
TRAINING: You will learn and be trained in a wide range of techniques, including stem cell culture, bioreactor design and development, biomaterials, microscopy, FACS, qPCR and Western analysis. A number of specific techniques such as intracellular nanoparticle reporters and mitochondrial analysis are currently being developed in our group, and you will be encouraged to develop your own unique skills portfolio, attend technical training courses and establish novel methods for conducting this highly original research. This project has excellent opportunities for extremely interdisciplinary doctoral training in tissue engineering, mechanical, electrical and systems engineering, clinical translation and fundamental stem cell biology. Our lab regularly attends UK and international conferences, and the successful student will have exceptionally good travel opportunities for collaborating with partner laboratories around the world and presenting their research.
BACKGROUND: Stem cell therapies have the potential to revolutionise the mass treatment of ageing, disease and trauma - but only if manufacturing costs can be substantially decreased. Scaling up regenerative cell therapies requires the introduction of novel techniques such as mechano-culture to harness the physical environment, rather than biochemical factors to drive cell growth. The dynamic mechanical environment in the body is an essential stimulus to drive cell growth – this is how exercise results in strong muscles, bones and joints. However, in laboratory culture and cell manufacturing this essential physical element is almost totally missing – this provides us an exciting opportunity with enormous commercial and clinical potential.
We have previously demonstrated that the mechanical conditions inside the cell culture growth environment can be easily manipulated using dynamic gas pressure to deliver growth stimuli to cells (see references). By harnessing this ‘unused’ extra dimension during culture we can exploit the stem cell’s ability to sense and respond to physical forces (exercise) to stimulate and accelerate cell growth. Therefore the substantial materials costs associated with GMP cell culture may be significantly reduced, cell growth and function enhanced, facilitating the wider availability of affordable cell-based therapies.
Our hypothesis is that hydrostatic pressure stimulates mechanotransduction pathways in the cell that promote growth, division and differentiation of human mesenchymal stem cells (hMSCs). Our aims are to demonstrate that mechanoculture-expanded cells maintain key stem cell markers and have improved functional characteristics (enhanced growth rates, differentiation capacity and a therapeutic secretome) compared to conventional T-flask passaged cells.
WORKPLACE: The Institute of Ageing and Chronic Disease is fully committed to promoting gender equality in all activities. In recruitment we emphasize the supportive nature of the working environment and the flexible family support that the University provides. The Institute holds a silver Athena SWAN award in recognition of on-going commitment to ensuring that the Athena SWAN principles are embedded in its activities and strategic initiatives.
The successful applicant will be expected to provide the funding for tuition fees and all living expenses as well as research and travel costs of £7,500 per year. There is NO funding attached to this project. Details of costs can be found on the University website.
1. Book chapter: Henstock JR (2017) ‘Bioreactors: recreating the biomechanical environment in vitro’ in Rawlinson SC (ed.) Mechanobiology: Exploitation for Medical Benefit, Wiley.
2. Leonard KHL, Henstock JR, El Haj AJ, Waters SL, Whiteley JP, Osborne JM (2016) The influence of hydrostatic pressure on tissue engineered bone development. Journal of Theoretical Biology 394, 149-59.
3. Foster NC, Henstock JR, Reinwald Y, El Haj AJ (2015) Dynamic 3D culture: Models of chondrogenesis and endochondral ossification. Birth Defects Res C: Embryo Today 105, 19-33.
4. Henstock JR, Rotherham M, Rose JB, El Haj AJ (2013) Cyclic hydrostatic pressure stimulates enhanced bone development in the foetal chick femur in vitro. Bone 53, 468 – 477.
How good is research at University of Liverpool in Clinical Medicine?
(joint submission with Liverpool School of Tropical Medicine)
FTE Category A staff submitted: 143.50
Research output data provided by the Research Excellence Framework (REF)
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