Transplantation of motoneurons derived from MASH1-transfected mouse ES cells reconstitutes neural networks and improves motor function in hemiplegic mice

Experimental Neurology
Ritsuko IkedaNoboru Suzuki

Abstract

Mouse embryonic stem (ES) cells were transfected with a MASH1 expression vector and G418-resistant cells were selected. The MASH1-transfected cells became neuron-like appearance and expressed betaIIItubulin and panNCAM. Glial fibrillary acidic protein (GFAP) and galactocerebroside (GalC)-expressing cells were rarely detected. Half of the neural cells differentiated into the Islet1+ motoneuron lineage. Thus, we obtained motoneuron lineage-enriched neuronal cells by transfection of ES cells with MASH1. A hemiplegic model of mice was developed by cryogenic injury of the motor cortex, and motoneuron lineage-enriched neuronal cells were transplanted underneath the injured motor cortex neighboring the periventricular region. The motor function of the recipients was assessed by a beam walking and rotarod tests, whereby the results gradually improved, but little improvement was observed in vehicle injected control mice. We found that the grafted cells not only remained close to the implantation site, but also exhibited substantial migration, penetrating into the damaged lesion in a directed manner up to the cortical region. Grafted neuronal cells that had migrated into the cortex were elongated axon-positive for neurofilament middle ch...Continue Reading

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Citations

Dec 15, 2007·Nature Reviews. Drug Discovery·Irina KlimanskayaRobert Lanza
Sep 20, 2008·Tissue Engineering. Part a·Stephanie M Willerth, Shelly E Sakiyama-Elbert
Apr 11, 2012·International Journal of Molecular Sciences·Nagisa ArimitsuNoboru Suzuki
Sep 11, 2014·Neural Regeneration Research·Daofang DingYongjun Wang
Jul 29, 2008·Journal of the Neurological Sciences·Miroslaw JanowskiBarbara Lukomska
Sep 15, 2007·Neuropathology and Applied Neurobiology·Y A ChristouP N Monk
Sep 14, 2017·Cell Transplantation·Noboru SuzukiTomoko Suzuki
Sep 24, 2005·Gene Therapy·J Polak, L Hench

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