Abstract
Primary cell transplantation is currently the gold standard for cell replacement in Parkinson’s disease. However, the number of donors needed to treat a single patient is high, and the functional outcome is sometimes variable. The present work explores the possibility of enhancing the viability and/or functionality of small amounts of ventral mesencephalic (VM) donor tissue by reducing its perturbation during preparation and implantation. Briefly, unilaterally lesioned rats received either: (1) an intact piece of half an embryonic day 13 (E13) rat VM; (2) dissociated cells from half an E13 rat VM; or (3) no transplant. D-amphetamine- induced rotations revealed that animals receiving pieces of VM tissue or dissociated cells showed significant improvement in ipsilateral rotation 4 weeks post transplantation. By 6 weeks post transplantation, animals receiving pieces of VM tissue showed a trend for further improvement, while those receiving dissociated cells remained at their 4 week scores. Postmortem cell counts showed that the number of dopaminergic neurons in dissociated cell transplants was significantly lower than that surviving in transplants of intact tissue. When assessing the correlation between the number of dopamine cells in each transplant, and the improvement in rotation bias in experimental animals, it was shown that transplants of whole pieces of VM tissue offered greater predictability of graft function based on their dopamine cell content. Such results suggest that maintaining the integrity of VM tissue during implantation improves dopamine cell content, and that the dopamine cell content of whole tissue grafts offers a more predictable outcome of graft function in an animal model of Parkinson’s disease.
Highlights
The development of primary cell transplantation as a therapeutic treatment for Parkinson’s disease (PD) has evolved a great deal since early studies provided proof for its potential efficacy in treating the disease clinically [1,2,3,4,5]
Though hopes remain for the generation of an unlimited source of dopamine neurons from a stem cell line [6,7], primary cell transplantation currently remains the gold standard for a cell replacement strategy in late stages of the disease, when the efficacy of pharmacological therapy wanes [2,3,8]
Animals were placed in groups so that the average rotation scores of the 3 groups before transplantation were: 12.2 tpm (+/21.42) for animals to be transplanted with pieces of tissue; 12.2 tpm (+/20.84) for those to be transplanted with dissociated cells; and 12.3 tpm (+/20.78) for control animals (Figure 1)
Summary
The development of primary cell transplantation as a therapeutic treatment for Parkinson’s disease (PD) has evolved a great deal since early studies provided proof for its potential efficacy in treating the disease clinically [1,2,3,4,5]. Have indicated that anywhere between 1 to 8 embryonic donors might be needed to treat a single patient via primary cell transplantation [12], each of which should be within a narrow time window of gestation. If primary cell transplantation is to become more practical for widespread use, the yield of tissue from each donor will have to be maximised, and the transplanted tissue will have to provide more consistent outcomes
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