title: Tracking induced pluripotent stem cells-derived neural stem cells in the central nervous system of rats and monkeys.
abstract: Despite of the immense breakthroughs of induced pluripotent stem cells (iPSCs), clinical application of iPSCs and their derivates remains hampered by a lack of definitive in vivo studies. Here, we attempted to track iPSCs-derived neural stem cells (NSCs) in the rodent and primate central nervous system (CNS) and explore their therapeutic viability for stem cell replacement in traumatic brain injury (TBI) rats and monkeys with spinal cord injury (SCI). Superparamagnetic iron oxide (SPIO) particles were used to label iPSCs-derived NSCs in vitro. Labeled NSCs were implanted into TBI rats and SCI monkeys 1 week after injury, and then imaged using gradient reflection echo (GRE) sequence by 3.0T magnetic resonance imaging (MRI) scanner. MRI analysis was performed at 1, 7, 14, 21, and 30 days, respectively, following cell transplantation. Pronounced hypointense signals were initially detected at the cell injection sites in rats and monkeys and were later found to extend progressively to the lesion regions, demonstrating that iPSCs-derived NSCs could migrate to the lesion area from the primary sites. The therapeutic efficacy of iPSCs-derived NSCs was examined concomitantly through functional recovery tests of the animals. In this study, we tracked iPSCs-derived NSCs migration in the CNS of TBI rats and SCI monkeys in vivo for the first time. Functional recovery tests showed obvious motor function improvement in transplanted animals. These data provide the necessary foundation for future clinical application of iPSCs for CNS injury.
authors.affiliation: 1 Department of Neurosurgery, Huashan Hospital, Fudan University , Shanghai, 200040, China .
authors.forename: Hailiang
authors.initials: H
authors.lastname: Tang
authors.forename: Hongying
authors.initials: H
authors.lastname: Sha
authors.forename: Huaping
authors.initials: H
authors.lastname: Sun
authors.forename: Xing
authors.initials: X
authors.lastname: Wu
authors.forename: Liqian
authors.initials: L
authors.lastname: Xie
authors.forename: Pu
authors.initials: P
authors.lastname: Wang
authors.forename: Chengshi
authors.initials: C
authors.lastname: Xu
authors.forename: Christian
authors.initials: C
authors.lastname: Larsen
authors.forename: Helen L
authors.initials: HL
authors.lastname: Zhang
authors.forename: Ye
authors.initials: Y
authors.lastname: Gong
authors.forename: Ying
authors.initials: Y
authors.lastname: Mao
authors.forename: Xiancheng
authors.initials: X
authors.lastname: Chen
authors.forename: Liangfu
authors.initials: L
authors.lastname: Zhou
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Feng
authors.forename: Jianhong
authors.initials: J
authors.lastname: Zhu
mesh_terms: D000818:Animals; D001483:Base Sequence; D001930:Brain Injuries / Q000628:therapy; D002478:Cells, Cultured; D002490:Central Nervous System / Q000166:cytology*; D017931:DNA Primers; D006801:Humans; D008253:Macaca mulatta; D008279:Magnetic Resonance Imaging; D008297:Male; D058953:Neural Stem Cells / Q000166:cytology*; D039904:Pluripotent Stem Cells / Q000166:cytology*; D016133:Polymerase Chain Reaction; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000628:therapy; D033581:Stem Cell Transplantation
chemical_list: D017931:DNA Primers
references.citation: Nat Biotechnol. 2009 Mar;27(3):275-80
references.pmid: 19252484
references.citation: Proc Natl Acad Sci U S A. 2004 Jul 27;101(30):10901-6
references.pmid: 15256592
references.citation: Cell. 2008 Feb 22;132(4):567-82
references.pmid: 18295576
references.citation: Nature. 2012 Jan 18;481(7381):295-305
references.pmid: 22258608
references.citation: Curr Protoc Mol Biol. 2005 Aug;Chapter 28:Unit 28.3
references.pmid: 18265368
references.citation: Nat Protoc. 2007;2(12):3081-9
references.pmid: 18079707
references.citation: Stem Cells. 2008 Feb;26(2):505-16
references.pmid: 17975226
references.citation: Brain Res. 1981 Apr 27;211(1):67-77
references.pmid: 7225844
references.citation: Cell. 2007 Nov 30;131(5):861-72
references.pmid: 18035408
references.citation: Science. 1996 Jul 26;273(5274):510-3
references.pmid: 8662542
references.citation: Neuroimage. 2006 Sep;32(3):1150-7
references.pmid: 16814567
references.citation: Cell Stem Cell. 2008 Jan 10;2(1):10-2
references.pmid: 18371415
references.citation: N Engl J Med. 2006 Nov 30;355(22):2376-8
references.pmid: 17135597
references.citation: Neurosurgery. 2001 Nov;49(5):1196-203; discussion 1203-4
references.pmid: 11846913
references.citation: Cell. 2006 Aug 25;126(4):663-76
references.pmid: 16904174
references.citation: J Neurosci Methods. 1991 Oct;39(3):253-62
references.pmid: 1787745
references.citation: Neuron. 2011 May 26;70(4):614-25
references.pmid: 21609820
references.citation: Neuroscience. 1997 Apr;77(3):875-88
references.pmid: 9070759
references.citation: J Physiol. 2007 Oct 1;584(Pt 1):25-30
references.pmid: 17690140