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Neuron. 2014 Aug 20;83(4):789-96. doi: 10.1016/j.neuron.2014.07.014. Epub 2014 Aug 7.

Long-distance axonal growth from human induced pluripotent stem cells after spinal cord injury.

Author information

1
Veterans Administration Medical Center, San Diego, CA 92161, USA; Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: plu@ucsd.edu.
2
Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
3
Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA.
4
Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
5
Veterans Administration Medical Center, San Diego, CA 92161, USA; Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: mtuszynski@ucsd.edu.

Abstract

Human induced pluripotent stem cells (iPSCs) from a healthy 86-year-old male were differentiated into neural stem cells and grafted into adult immunodeficient rats after spinal cord injury. Three months after C5 lateral hemisections, iPSCs survived and differentiated into neurons and glia and extended tens of thousands of axons from the lesion site over virtually the entire length of the rat CNS. These iPSC-derived axons extended through adult white matter of the injured spinal cord, frequently penetrating gray matter and forming synapses with rat neurons. In turn, host supraspinal motor axons penetrated human iPSC grafts and formed synapses. These findings indicate that intrinsic neuronal mechanisms readily overcome the inhibitory milieu of the adult injured spinal cord to extend many axons over very long distances; these capabilities persist even in neurons reprogrammed from very aged human cells.

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PMID:
25123310
PMCID:
PMC4144679
DOI:
10.1016/j.neuron.2014.07.014
[Indexed for MEDLINE]
Free PMC Article

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