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Comparison of Embryonic Stem Cell-Derived Dopamine Neuron Grafts and Fetal Ventral Mesencephalic Tissue Grafts: Morphology and Function

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Abstract:

In this study we compared the function and morphology of two types of neural grafts: allografts of fetal ventral mesencephalic (VM) tissue and xenografts of embryonic stem cell (ESC)-derived dopamine neurons. Mouse embryonic stem cells were cultured and exposed to differentiation factors that induced approximately 10% of the cells to express a dopaminergic phenotype. These cells were then harvested and implanted into the denervated striatum of rats with unilateral lesions of the nigrostriatal pathway. Another group of lesioned rats received allografts of fetal ventral mesencephalic tissue. While both types of grafts yield a similar number of tyrosine hydroxylase (TH)-positive cells, amphetamine-induced rotational behavior was differentially affected by these grafts: rotational behavior was significantly reduced in lesioned rats receiving allografts of fetal VM tissue while ESC grafts had slight but insignificant effects on rotational scores. Densitometry measures of TH+ fiber outgrowth revealed a similar area of reinnervation and a comparable number of TH+ cells for ESC graft when compared with VM grafts. These data suggest there are similarities and also distinct differences in the manner in which ESC and VM grafts interact with the denervated striatum.

Keywords: Dopamine; Neural transplantation; Parkinson’s disease; Rodent; Stem cells

Document Type: Research Article

DOI: http://dx.doi.org/10.3727/000000004783983954

Affiliations: Department of Surgery/Neurosurgery, University of Kentucky College of Medicine, Lexington, KY

Publication date: January 1, 2004

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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