Brain Advance Access originally published online on March 29, 2007
Brain 2007 130(5):1317-1329; doi:10.1093/brain/awm053
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Striatal graft projections are influenced by donor cell type and not the immunogenic background
1Brain Repair Group, School of Biosciences, Museum Avenue, Cardiff, CF10 3US, 2Department of Obstetrics and Gynaecology, University of Wales College of Medicine, Heath Park, Cardiff, CF14 4XN and 3Department of Neurology and Medical Genetics, University of Wales College of Medicine, Heath Park, Cardiff, CF14 4XN, UK
Correspondence to: Claire M. Kelly, Brain Repair Group, School of Biosciences, Museum Avenue, Cardiff, CF10 3US, UK E-mail: kellycm{at}cf.ac.uk
Reconstruction of CNS circuitry is a major aim of neural transplantation, and is currently being assessed clinically using foetal striatal tissue in Huntington's disease. Recent work suggests that neuronal precursors derived from foetal striatum may have a greater capacity than primary foetal striatum to project to the usual striatal target areas such as the globus pallidus and substantia nigra, raising the possibility that they have a greater potential for circuit reconstruction. However, comparing the reconstructive capacity of the two donor cells types is confounded by the fact that many precursor experiments have been carried out in a xenogeneic background in order to utilize species-specific markers for tracking the donor cells, whereas most primary foetal transplant studies have utilized an allograft paradigm. Thus, differences in immunogenic background could influence the findings; for example, xenogeneic grafts may not recognize host inhibitory signals, thereby encouraging more profuse and extensive projections. We have addressed this issue directly by comparing foetal neural precursor and primary foetal grafts in both allo- and xenograft environments using several labelling techniques, including GFP-transgenic mice and LacZ-labelled cells as donor tissue and iontophoretic injection of the anterograde tracers BDA, neurobiotin and PHA-L in the host. We present clear evidence that foetal neural precursors produce grafts with richer axonal outgrowth than primary foetal grafts, and that this is independent of the immunogenic background. Furthermore, both neural precursor and primary grafts derived from human foetal tissue produced a significantly richer outgrowth than do grafts of mouse donor tissue, which may relate to their large final graft volume and the greater intrinsic potential of human CNS neurons for greater axon elongation.
Key Words: allograft; xenograft; transplantation; precursor cells
Abbreviations: BDA, biotynilated dextran amine; FNP, foetal neural precursor; NBT, neurobiotin
Received October 30, 2006. Revised February 23, 2007. Accepted February 26, 2007.
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