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Open Access Multitract Microtransplantation Increases the Yield of DARPP-32-Positive Embryonic Striatal Cells in a Rodent Model of Huntington's Disease

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Abstract:

Embryonic striatal graft-mediated functional recovery in the rodent lesion model of Huntington's disease (HD) has been shown to correlate with the proportion of dopamine- and adenosine 3′,5′-monophosphate-regulated phosphoprotein with a molecular weight of 32 kDa (DARPP-32)-positive neurons in the graft. The current study investigated the impact of graft distribution on the yield of DARPP-32-positive cells in the grafts following either single-tract or multitract cell delivery protocols using the microtransplantation approach. Cells derived from the whole ganglionic eminence of E15 rat embryos, ubiquitously expressing green fluorescent protein (GFP), were implanted into unilaterally QA-lesioned rat striatum either as 2 × 1.8 μl macrodeposits in a single tract, or as 18 × 0.2 μl microdeposits disseminated over six needle, multitract, penetrations. For both groups, an ultrathin glass capillary with an outer diameter of 50 μm was used. Histological assessment at 4 months after transplantation showed nearly twofold increase of DARRP-32-positive striatal-like neurons in the multitract compared to the single-tract group. However, the cellular make-up of the grafts did not translate into functional differences as tested in a basic spontaneous behavior test. Furthermore, the volumetric values for overall volume, DARPP-32-positive patches, and dopaminergic projection zones were similar between both groups. The results show that distribution of fetal striatal tissue in multiple submicroliter deposits provides for an increased yield of striatal-like neurons, potentially due to the enlargement of the graft‐host border area intensifying the graft's exposure to host-derived factors. Furthermore, the use of embryonic tissue from GFP donors was validated in cell-based therapy studies in the HD model.

Keywords: Embryonic striatal neurons; Green fluorescent protein (GFP); Huntington's disease model; Microtransplantation; Multitract

Document Type: Research Article

DOI: https://doi.org/10.3727/096368910X547435

Affiliations: Laboratory of Molecular Neurosurgery, Department of Stereotactic and Functional Neurosurgery, Neurocentre, Albert-Ludwigs-University of Freiburg, Freiburg, Germany

Publication date: 2011-10-01

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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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