@article{12587d5e75b14d3ab367bd22e3fc4d10,
title = "Generation and post-injury integration of human spinal cord neural stem cells",
abstract = "Spinal cord neural stem cells (NSCs) have great potential to reconstitute damaged spinal neural circuitry, but they have yet to be generated in vitro. We now report the derivation of spinal cord NSCs from human pluripotent stem cells (hPSCs). Our observations show that these spinal cord NSCs differentiate into a diverse population of spinal cord neurons occupying multiple positions along the dorso-ventral axis, and can be maintained for prolonged time periods. Grafts into injured spinal cords were rich with excitatory neurons, extended large numbers of axons over long distances, innervated their target structures, and enabled robust corticospinal regeneration. The grafts synaptically integrated into multiple host intraspinal and supraspinal systems, including the corticospinal projection, and improved functional outcomes after injury. hPSC-derived spinal cord NSCs could enable a broad range of biomedical applications for in vitro disease modeling and constitute an improved clinically translatable cell source for {\textquoteleft}replacement{\textquoteright} strategies in several spinal cord disorders.",
author = "Hiromi Kumamaru and Ken Kadoya and Adler, {Andrew F.} and Yoshio Takashima and Lori Graham and Giovanni Coppola and Tuszynski, {Mark H.}",
note = "Funding Information: We thank P. Lu, J. Dulin, C. Lee-Kubli, and E. Staufenberg for experimental assistance; R. Kawaguchi and F. Gao for analysis of RNA-seq data; R.C. Addis (University of Pennsylvania, Philadelphia, PA, USA) for providing lentivirus expressing GCaMP5; S. Fisher (UCSF, San Francisco, CA, USA) for providing UCSF4 hESCs; T. M{\"u}ller and C. Birchmeier (Max Delbr{\"u}ck Center for Molecular Medicine, Berlin, Germany) for providing TLX3 and LBX1 antibodies; S. Ross (University of Pittsburgh, Pittsburgh, PA, USA) for providing BHLHB5 antibody; and R. Darnell (the Rockefeller University, New York, NY, USA) for providing Hu antibody. This work was supported by the Veterans Administration Gordon Mansfield Spinal Cord Injury Consortium (to M.H.T.), the NIH (grants NS042291 and EB014986 to M.H.T.), the Craig H. Neilsen Foundation (to H.K. and K.K.), the Japan Society for the Promotion of Science (to H.K.), the Bernard and Anne Spitzer Charitable Trust (to M.H.T.), and the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (to M.H.T.). Publisher Copyright: {\textcopyright} 2018, The Author(s).",
year = "2018",
month = sep,
day = "1",
doi = "10.1038/s41592-018-0074-3",
language = "English",
volume = "15",
pages = "723--731",
journal = "Nature Methods",
issn = "1548-7091",
publisher = "Nature Publishing Group",
number = "9",
}
