Stem and progenitor cells for brain repair
The stem cell project is coordinated by Professor Anne Rosser, in collaboration with Steve Dunnett, Nick Allen and Professor Sir Martin Evans, all within the School of Biosciences.
To develop alternative sources of stable quality-assured cells for
application in human clinical transplantation programmes.
Present clinical transplantation trials are based on use of primary human fetal tissues. This source of donor cells is impractical for widespread application, not only because of ethical concerns but also because of their limited availability, difficult logistics and quality-control issues.
We seek to develop alternative sources of cells, most probably based on embryonic stem, germ line or fetal progenitor cell lines that can be expanded long-term and differentiated into neurones in vitro. The major focus of the research projects of the lab is to understand the principles associated with normal development to identify phenotypic markers and signals that can be used to drive cell differentiation down the precise and specific lineages required for the cells to be suitable for functional repair, first in experimental studies and subsequently for clinical application.
Studies are undertaken in rodent and human cells in parallel. This has required establishing an ethically approved programme for human fetal donor tissue donation (SWIFT, the South Wales Initiative for Transplantation) in collaboration with the Department of Obstetrics & Gynaecology at the Wales University Hospital, alongside the implementation and validation of a GMP (‘Good Manufacturing Practice’) laboratory, for processing cells for clinical application under pharmaceutical grade conditions, pending MHRA accreditation.
Selected recent publications
- Rosser AE, Allen ND (2006) Help for Huntington's: stem cells for neurodegenerative disease. The Biochemist 28: 19-24.
- Kelly CM, Tyers P, ter Borg M, Svendsen CN, Dunnett SB, Rosser AE (2005) EGF and FGF-2 responsiveness of rat and mouse neural precursors derived from embryonic CNS. Brain Res Bull 68: 83-94.
- Zietlow R, Pekarik V, Armstrong RJE, Tyers P, Dunnett SB, Rosser AE (2005) The survival of neural precursor cell grafts is influenced by in vitro expansion. J Anat 207: 227-240.
- Armstrong RJE, Tyers P, Jain M, Richards A, Dunnett SB, Rosser AE, Barker RA (2003) Transplantation of expanded neural precursor cells from the developing pig ventral mesencephalon in a rat model of Parkinson's disease. Exp Brain Res 151: 204-217.
- Jain M, Armstrong RJE, Elneil S, Rosser AE, Barker RA (2003) Migration and differentiation of transplanted human neural precursor cells. NeuroReport 14: 1257-1262.
- Jain M, Armstrong RJE, Tyers P, Barker RA, Rosser AE (2003) GABAergic immunoreactivity is predominant in neurons derived from expanded human neural precursor cells in vitro. Exp Neurol 182: 113-123.
- Kelly CM, Zietlow R, Dunnett SB, Rosser AE (2003) The effects of various concentrations of FGF-2 on the proliferation and neuronal yield of murine embryonic neural precursor cells in vitro. Cell Transplant 12: 215-223.
- Rosser AE, Tyers P, ter Borg M, Caldwell M, Svendsen CN (2003) Gestational age determines the response in vitro of rat embryonic neural precursor cells to epidermal growth factor and fibroblast growth factor-2. Mol Cell Neurosci in press.
- Armstrong RJE, Hurelbrink CB, Tyers P, Ratcliffe EL, Richards A, Dunnett SB, Rosser AE, Barker RA (2002) The potential for circuit reconstruction by expanded neural precursor cells explored through porcine xenografts in a rat model of Parkinson's disease. Exp Neurol 175: 98-111.
- Armstrong RJE, Harrower TP, Mclaughlin M, Hurelbrink CB, Ratcliffe EL, Tyers P, Richards A, Dunnett SB, Rosser AE, Barker RA (2001) Porcine neural xenograftsin the immunocompetent rat: immune response following grafting of expanded neural precursor cells. Neuroscience 106: 201-216.
- Armstrong RJE, Watts C, Svendsen CN, Dunnett SB, Rosser AE (2000) Survival, neuronal integration and fibre outgrowth of propagated human neural precursor grafts in an animal model of Huntington's disease. Cell Transplant 9: 55-64.
- Rosser AE, Tyers P, Dunnett SB (2000) The morphological development of neurons derived from EGF- and FGF-2-driven human CNS precursors depends on their site of integration in the neonatal rat brain. Eur J Neurosci 12: 2405-2413.
- Svendsen CN, ter Borg M, Armstrong RA, Rosser AE, Chandran S, Ostenfeld T, Caldwell MA (1998) A new method for the rapid and long term growth of human neural precursor cells. J Neurosci Meth 85: 141-152.