Scheme: University Research Fellowship
Organisation: Cardiff University
Dates: Oct 2010-Sep 2014
Summary: Stem cells are special cells with unlimited self-renew capacity and can differentiate into diverse lineages and cell types. Stem cells replacement therapy has long been suggested to be potentially beneficial in treating central nervous system diseases, for example spinal cord injury.
3 main cellular events must be precisely regulated before any meaningful clinical stem cell based replacement therapy can take place, namely cell migration, division and differentiation. This can sometimes proves to be very difficult due to: 1).cell migration / division / differentiation are largely coordinated events (one depending on the regulating of the other); 2). The complex molecular mechanisms involved in such regulation; and 3). How to optimise the most suitable stem cell types for transplantation in order to bypass the ethical issue.
In our previous studies, we demonstrated that electric signals could effectively regulate the directed cell migration of neural stem cells, and we proved that this can be precisely controlled in not only single cells, cluster of cells as collective cell migration, and in a 3D spinal cord tissue culture model. We demonstrated that both neural stem cell migration and differentiation can be controlled under the treatment of physiological electric stimulation in both 2D and 3D environment, which is closely regulated by multiple signalling pathways, which have been previously proved to be essential in the regulation of multiple cellular events in neuronal development.
We also demonstrated that not only the migration / differentiation of neural stem cells are regulated by electric signals, but also the cell division orientation as well. Modulating electric signals strength could accordingly regulate the neural stem cells division, which potentially could have profound effect in the determination of the stem cells differentiation. We are currently investigating the genetic / molecular regulators of such events.
Dates: Oct 2005-Sep 2010
Summary: Millions of people worldwide suffer from central nervous system injury, leading to subsequent poor quality of lives. The treatment of brain and spinal cord injury (SCI) is extremely difficult, due to the limited capacity of brain / spinal cord to self-renew themselves. Stem cells replacement has huge potential in treating SCI or brain injury, we propose to investigate the control mechanisms of cell division / migration of the neural stem cells, in order to optimise their potential in stem cell replacement therapy. This is a highly challenging and rewarding project using unconventional approaches of multi-disciplinary studies combining electric signalling and nanotechnology, to investigate the molecular and genetic control mechanisms of neural stem cell division and migration. This project will have extraordinary impact into both basic scientific research of neural stem cell division and migration control, and potential clinical treatments using stem cells replacement therapies for neurodegenerative diseases. This project will fully reveal the role of electric signals in regulating division and migration of neural stem cells in both 2D and 3D cultures, and dissect the division / migration behaviours of transplanted neural stem cells in several wound models. It will provide extensive information on molecular and genetic mechanisms of electric signals controlled division / migration of stem cells, and the potential interactions between electric signals and chemical guidance cues. This project will establish the ground rules of electrical-based therapies in treating devastating central nervous system injury, and bring an exciting new tool to the clinical treatment for neurodegenerative diseases using a combination of nanotechnology and electric signals, and neural stem cells replacement therapies.