title: Long-distance axonal growth from human induced pluripotent stem cells after spinal cord injury.
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.
authors.affiliation: 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.
authors.forename: Paul
authors.initials: P
authors.lastname: Lu
authors.affiliation: Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Grace
authors.initials: G
authors.lastname: Woodruff
authors.affiliation: Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Yaozhi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Lori
authors.initials: L
authors.lastname: Graham
authors.affiliation: Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Matt
authors.initials: M
authors.lastname: Hunt
authors.affiliation: Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Di
authors.initials: D
authors.lastname: Wu
authors.affiliation: Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Eileen
authors.initials: E
authors.lastname: Boehle
authors.affiliation: Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Ruhel
authors.initials: R
authors.lastname: Ahmad
authors.affiliation: Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Poplawski
authors.affiliation: Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: John
authors.initials: J
authors.lastname: Brock
authors.affiliation: 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.
authors.forename: Lawrence S B
authors.initials: LS
authors.lastname: Goldstein
authors.affiliation: 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.
authors.forename: Mark H
authors.initials: MH
authors.lastname: Tuszynski
mesh_terms: D000369:Aged, 80 and over; D000818:Animals; D001369:Axons / Q000502:physiology* / Q000648:ultrastructure; D002454:Cell Differentiation / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D002574:Cervical Vertebrae; D005260:Female; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000637:transplantation* / Q000648:ultrastructure; D008297:Male; D009416:Nerve Regeneration / Q000502:physiology*; D051381:Rats; D013119:Spinal Cord Injuries / Q000601:surgery*