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The Effects of Transforming Growth Factor-β2 on Dopaminergic Graft Survival

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Dopaminergic cell transplantation is a promising therapeutic approach for the treatment of Parkinson’s disease, the potential of which is limited due to poor survival and low dopamine content within engrafted tissue. In this study, the ability of transforming growth factor-β2 (TGF-β2) to influence transplant survival was evaluated. Cell suspensions containing fetal rat ventral mesencephalon (VM) cells were incubated prior to surgery with vehicle (DPBS), varying concentrations of TGF-β2 (5–1000 ng/ml), or a pan-specific antibody against TGF-β (1D11, 100 ng/ml). VM cell suspensions (200,000 cells) were unilaterally implanted into the striatum of adult Sprague-Dawley rats (n = 5–11 animals/group). Following a 3-week survival period, small but viable VM grafts containing tyrosine hydroxylase-positive (TH+) neurons and fibers were present in all animals. Addition of TGF-β2 resulted in a steep, bell-shaped dose–response curve with a significant effect on TH+/dopamine cell survival. At 50 ng/ml TGF-β2, the number of surviving dopamine neurons was increased twofold compared with controls. Addition of TGF-β2 or 1D11 did not significantly influence graft volume. Further studies, possibly in combination with other neurotrophic factors, need to be performed to obtain a greater understanding of the effects of TGF-β on dopamine neurons and fetal VM cell engraftment.

Keywords: Neuroprotection; Neurotrophic; Parkinson’s disease; TGF-β; Transplantation

Document Type: Research Article


Affiliations: 1: *Genzyme Corporation, Framingham, MA 01701 2: †University Hospital Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands 3: ‡VU Medisch Centrum, Amsterdam, The Netherlands

Publication date: January 1, 2004

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  • 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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