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Human adipose-Derived Mesenchymal Stem Cells Improve Motor Functions and are Neuroprotective in the 6-Hydroxydopamine-Rat Model for Parkinson’s Disease when Cultured in Monolayer Cultures but Suppress Hippocampal Neurogenesis and Hippocampal Memory Function when Cultured in Spheroids

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Abstract

Adult human adipose-derived mesenchymal stem cells (MSC) have been reported to induce neuroprotective effects in models for Parkinson´s disease (PD). However, these effects strongly depend on the most optimal application of the transplant. In the present study we compared monolayer-cultured (aMSC) and spheroid (sMSC) MSC following transplantation into the substantia nigra (SN) of 6-OHDA lesioned rats regarding effects on the local microenvironment, degeneration of dopaminergic neurons, neurogenesis in the hippocampal DG as well as motor and memory function in the 6-OHDA-rat model for PD. aMSC transplantation significantly increased tyrosine hydroxylase (TH) and brain-derived neurotrophic factor (BDNF) levels in the SN, increased the levels of the glial fibrillary acidic protein (GFAP) and improved motor functions compared to untreated and sMSC treated animals. In contrast, sMSC grafting induced an increased local microgliosis, decreased TH levels in the SN and reduced numbers of newly generated cells in the dentate gyrus (DG) without yet affecting hippocampal learning and memory function. We conclude that the neuroprotective potential of adipose-derived MSC in the rat model of PD crucially depends on the applied cellular phenotype.

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Acknowledgments

The authors thank Renate Winter for excellent technical assistance. The study was funded by the EFRE grant of the Investitionsbank Berlin to BS.

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Authors and Affiliations

  1. Department of Neurology, Charité University Medicine Berlin, CCM, Charitéplatz 1, D-10117, Berlin, Germany

    Jürgen Berg, Jennifer Altschüler, Anne Schwerk & Barbara Steiner

  2. Institute for Immunology, Charité University Medicine Berlin, Augustenburger Platz 1, D-13353, Berlin, Germany

    Manfred Roch & Andreas Kurtz

  3. Department of Psychiatry, University Hospital Carl Gustav Carus, Technical University Dresden, Fetscherstr. 74, D-01307, Dresden, Germany

    Christine Winter

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  1. Jürgen Berg
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Correspondence to Barbara Steiner.

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Berg, J., Roch, M., Altschüler, J. et al. Human adipose-Derived Mesenchymal Stem Cells Improve Motor Functions and are Neuroprotective in the 6-Hydroxydopamine-Rat Model for Parkinson’s Disease when Cultured in Monolayer Cultures but Suppress Hippocampal Neurogenesis and Hippocampal Memory Function when Cultured in Spheroids. Stem Cell Rev and Rep 11, 133–149 (2015). https://doi.org/10.1007/s12015-014-9551-y

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