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March 08, 2016

One step closer to cell therapy for motor neurons

Scientists at CiRA discover a new molecule that induces motor neurons from pluripotent stem cells and has implications in cell therapies

The degeneration or death of cortical motor neurons (CMNs) is associated with diseases like amyotrophic lateral sclerosis and other forms of paralysis. Continuing evidence has suggested that stem cell therapy offers a way to recover the lost CMNs and help patients acquire normal movement. Before transplantation, the stem cells are differentiated into CMN progenitors that then go on to produce ample CMNs in the body. However, protocols for this differentiation are not suitable for patient care. "No lab has had good success inducing CMNs from stem cells," explains Professor Jun Takahashi of CiRA. Using human induced pluripotent stem (iPS) cells, the Takahashi lab has discovered a new molecule, C59, significantly enhances the differentiation efficiency. The scientists compared protocols that used C59 with other chemicals commonly used to prepare cortical neurons. When transplanted into the brains of living mice, those made with C59 showed more axonal extensions to the spinal cord. They further showed that at the molecular level, C59 inhibits canonical and non-canonical Wnt signaling, whereas the chemicals used in other protocols only inhibit canonical Wnt signaling. "This finding gives a new explanation on how CMNs develop," says Takahashi, and is expected to improve CMN differentiation from stem cells for cell therapies.

Paper Details
Journal: Stem Cells Translational Medicine
DOI: 10.5966/sctm.2015-0261
Title: Induction of anterior cortex from stem cells
Authors: Makoto Motono(1), Yoshihiko Ioroi(1), Takenori Ogura(1), Jun Takahashi(1,2)
Author Affiliations:
1. Center for iPS Cell Research and Application (CiRA), Kyoto University
2. Department of Neurosurgery, Graduate School of Medicine, Kyoto University
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