14-07-08(10:37:38)
Authors:
Kelly, C.M.1, Precious, S.V.1, Lane, E.1, Scherf, C. 2, Williams, D. 2, Torres, E., Weyrauch, U. 1, Daly, C. 1, Baird, A. 1, Penketh, R. 2, Amso, N.N. 2, Dunnett, S.B. 1, Rosser, A.E. 1,3
Institutions:
1 Brain Repair Group, School of Biosciences, Cardiff University, Museum Avenue, Cardiff, CF10 3US.
2 Department of Obstetrics and Gynaecology, School of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN.
3 Departments of Neurology and Genetics, School of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN.
Title of abstract : Medical termination of pregnancy as a source of tissue for cell replacement therapies.
Abstract text:
Cell replacement therapy for neurodegenerative disorders such as Parkinson’s (PD) and Huntington’s disease (HD) is an attractive therapeutic strategy, with clinical studies using fetal brain tissue as the donor source having demonstrated ‘proof of principle’. However, therapeutic application will be limited by the scarcity of fetal tissue of the appropriate gestational age and quality. To date, the successful clinical studies have used tissue collected from surgical terminations of pregnancy (TOP), which is limited in its availability. An alternative is to collect tissue from medical TOP, which is now becoming the method of choice in most centres in the UK. Medical TOPs are induced by the administration of an anti-progestogen in combination with a prostoglandin 48 hours later, which then leads to the spontaneous expulsion of the products of conception, which usually remain largely intact. This is in contrast to surgical TOPs, which involves manual low-pressure aspiration with a gynaecological syringe and cannula and almost always results in tissue fragmentation, rendering accurate dissection difficult. The delay between initiation of the process of medical TOP and tissue collection raised concerns that cell viability would be affected. We compared retrieval of fetal brain tissue retrieved through medical and surgical TOPs and tested for viability and differentiation potential both in vitro and in vivo in models of HD and PD. We have found that the neural tissues of interest obtained from medical TOPs are more readily identifiable than those collected through the surgical route, thus producing a much higher yield of identifiable CNS regions. The range of cell viability of dissociated tissue tends to be greater, but in our sample approximately 60% had viability over 80% and overall medical TOPs yielded substantially more tissue suitable for transplantation than did surgical TOP. We believe medical TOP may provide a more reliable and readily available source of tissue for cell replacement in neurodegenerative conditions such as HD and PD.
