Transplanted Human Neural Precursor Cells Migrate Widely But Show no Lesion-Specific Tropism in the 6-Hydroxydopamine Rat Model of Parkinson's Disease

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Abstract:

Parkinson's disease (PD), while primarily associated with degeneration of nigrostriatal dopamine neurons, is now increasingly recognized to have more widespread cell loss and so the most effective cell replacement therapy should target all these neuronal losses. Neural precursor cells might be ideal in this regard as in certain circumstances they have been shown to migrate widely following transplantation into the CNS. The aim of this study was to investigate whether transplanted human expanded neural precursor cells (hENPs) could migrate to sites of established or evolving pathology in the adult brain using the 6-hydroxydopamine (6-OHDA) rat model of PD. hENPs were grafted into the striatum prior to, at the same time as, or after the animals received a 6-OHDA lesion to the medial forebrain bundle. The presence of donor cells was then assessed in a distant site of cell loss (substantia nigra) or sites where cell death would not be expected (frontal cortex and globus pallidus). Donor cells were found distant from the site of implantation but the migration of these hENPs was not significantly greater in the 6-OHDA-lesioned brain and the cells did not specifically target the site of cell loss in the substantia nigra. The temporal relationship of grafting relative to the lesion, and therefore dopaminergic cell death, did not affect the migration of hENPs nor their differentiation. We conclude that while transplanted hENPs are capable of migration away from the site of implantation, they show no specific tropism for sites of ongoing or established nigral dopaminergic cell loss in this lesion model. Therefore, the use of such cells to replace the range of neurons lost in PD is likely to require a deeper understanding of the migratory cues in the damaged adult brain and some manipulation of these cells prior to transplantation.

Keywords: Cortex; Migration; Neural stem cells; Neural transplantation; Progenitor cells; Substantia nigra

Document Type: Research Article

DOI: http://dx.doi.org/10.3727/000000006783981684

Affiliations: 1: Cambridge University Centre for Brain Repair, Forvie Site, Robinson Way, Cambridge CB2 2PY, UK 2: Department of Obstetrics and Gynaecology, Level 2, The Rosie Hospital, Robinson Way, Cambridge, CB2 2SW, UK 3: Cambridge University Centre for Brain Repair, Forvie Site, Robinson Way, Cambridge CB2 2PY, UK, Department of Neurology, Addenbrookes Hospital, Hills Road, Cambridge, CB2 2QQ, UK

Publication date: July 1, 2006

More about this publication?
  • Cell Transplantation publishes original, peer-reviewed research and review articles on the subject of cell transplantation and its application to human diseases. To ensure high-quality contributions from all areas of transplantation, separate section editors and editorial boards have been established. Articles deal with a wide range of topics including physiological, medical, preclinical, tissue engineering, and device-oriented aspects of transplantation of nervous system, endocrine, growth factor-secreting, bone marrow, epithelial, endothelial, and genetically engineered cells, among others. Basic clinical studies and immunological research papers are also featured. To provide complete coverage of this revolutionary field, Cell Transplantation will report on relevant technological advances, and ethical and regulatory considerations of cell transplants. Cell Transplantation is now an Open Access journal starting with volume 18 in 2009, and therefore there will be an inexpensive publication charge, which is dependent on the number of pages, in addition to the charge for color figures. This will allow work to be disseminated to a wider audience and also entitle the corresponding author to a free PDF, as well as prepublication of an unedited version of the manuscript.
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