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  • Title: Potential use of embryonic stem cells for the treatment of mouse parkinsonian models: improved behavior by transplantation of in vitro differentiated dopaminergic neurons from embryonic stem cells.
    Author: Nishimura F, Yoshikawa M, Kanda S, Nonaka M, Yokota H, Shiroi A, Nakase H, Hirabayashi H, Ouji Y, Birumachi J, Ishizaka S, Sakaki T.
    Journal: Stem Cells; 2003; 21(2):171-80. PubMed ID: 12634413.
    Abstract:
    BACKGROUND: and Aims. The purpose of the present study was to examine the efficacy of transplantation of mouse embryonic-stem-(ES)-cell-derived tyrosine hydroxylase-positive (TH(+)) cells into Parkinsonian mice using behavioral tests and immunohistochemical evaluation. METHODS: Undifferentiated ES cells carrying the enhanced green fluorescent protein (EGFP) gene were differentiated into a cell population containing TH(+) neurons using a five-step in vitro differentiation method. These ES-cell-derived cells were used as allografts in Parkinsonian mice, made by administering injections of 6-hydroxydopamine (6-OHDA). Fifteen hemiparkinsonian mice were divided into three groups. Four weeks after 6-OHDA injection, mice in groups 1, 2, and 3 received phosphate-buffered saline, 1 x 10(4) graft cells, and 1 x 10(5) graft cells, respectively, into their dopamine-denervated striata. RESULTS: Improved rotational behavior was observed in the graft-transplanted groups (groups 2 and 3) 2 weeks after transplantation. Mice in group 2 displayed a continuous maintenance of reduced rotational behavior, while those in group 3 showed ipsilateral rotation toward the lesioned side at 4, 6, and 8 weeks after transplantation. Tumor formation was observed in one mouse in group 3. TH(+) cells were found at the grafted sites 8 weeks after transplantation in mice in groups 2 and 3, some of which were immunopositive to GFP, demonstrating the presence of dopaminergic neurons derived from the ES cells. CONCLUSION: Transplantation of in vitro differentiated ES cells changed rotational behavior in Parkinsonian mice. Our results suggest the potential availability of ES cells for Parkinson's disease.
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