Article
Multi-tract microtransplantation increases the yield of DARPP-32 positive embryonic striatal cells in a rodent model of Huntington's disease
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Published: | September 16, 2010 |
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Objective: Embryonic striatal tissue mediated functional recovery in the rodent lesion model of Huntington's disease (HD) correlates with the proportion of dopamine- and adenosine 3',5'-monophosphat-regulated phosphoprotein with a molecular weight of 32 kDa (DARPP-32) positive neurones in the graft. The current study investigated the impact of the microtransplantation procedure by comparing the DARPP-32 positive cell numbers in the grafts following either single-tract or multi-tract cell delivery protocols.
Methods: 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 x 1.8 μl deposits in a single-tract, or as 18 x 0.2 μl deposits disseminated over six needle, multi-tract, penetrations. For both groups, an ultra-thin glass capillary with an outer diameter of 50 μm was used.
Results: Histological assessment at 4 months after transplantation showed nearly two-fold increase of DARRP-32 positive striatal like neurons in the multi-tract compared to the single-tract group. Multi-tract grafts tended to have larger overall volumes, increased DARPP-32 positive zones and were more extensively innervated by dopaminergic projections. However, the cellular make-up of the grafts did not translate into functional differences as tested in simple spontaneous behaviour tests.
Conclusions: 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.