title: Engrafted human induced pluripotent stem cell-derived anterior specified neural progenitors protect the rat crushed optic nerve.
abstract: BACKGROUND
  Degeneration of retinal ganglion cells (RGCs) is a common occurrence in several eye diseases. This study examined the functional improvement and protection of host RGCs in addition to the survival, integration and neuronal differentiation capabilities of anterior specified neural progenitors (NPs) following intravitreal transplantation.
  
  
  RESULTS
  NPs were produced under defined conditions from human induced pluripotent stem cells (hiPSCs) and transplanted into rats whose optic nerves have been crushed (ONC). hiPSCs were induced to differentiate into anterior specified NPs by the use of Noggin and retinoic acid. The hiPSC-NPs were labeled by green fluorescent protein or a fluorescent tracer 1,1' -dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) and injected two days after induction of ONC in hooded rats. Functional analysis according to visual evoked potential recordings showed significant amplitude recovery in animals transplanted with hiPSC-NPs. Retrograde labeling by an intra-collicular DiI injection showed significantly higher numbers of RGCs and spared axons in ONC rats treated with hiPSC-NPs or their conditioned medium (CM). The analysis of CM of hiPSC-NPs showed the secretion of ciliary neurotrophic factor, basic fibroblast growth factor, and insulin-like growth factor. Optic nerve of cell transplanted groups also had increased GAP43 immunoreactivity and myelin staining by FluoroMyelin™ which imply for protection of axons and myelin. At 60 days post-transplantation hiPSC-NPs were integrated into the ganglion cell layer of the retina and expressed neuronal markers.
  
  
  CONCLUSIONS
  The transplantation of anterior specified NPs may improve optic nerve injury through neuroprotection and differentiation into neuronal lineages. These NPs possibly provide a promising new therapeutic approach for traumatic optic nerve injuries and loss of RGCs caused by other diseases.
authors: Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
authors: Leila
authors: L
authors: Satarian
authors: Mohammad
authors: M
authors: Javan
authors: Sahar
authors: S
authors: Kiani
authors: Maryam
authors: M
authors: Hajikaram
authors: Javad
authors: J
authors: Mirnajafi-Zadeh
authors: Hossein
authors: H
authors: Baharvand
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002465:Cell Movement; D002470:Cell Survival; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D019610:Cytoprotection; D005074:Evoked Potentials, Visual; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000502:physiology*; D008297:Male; D009414:Nerve Growth Factors / Q000378:metabolism; D009416:Nerve Regeneration; D058953:Neural Stem Cells / Q000502:physiology* / Q000637:transplantation; D009900:Optic Nerve / Q000473:pathology / Q000503:physiopathology; D020221:Optic Nerve Injuries / Q000503:physiopathology / Q000628:therapy*; D051381:Rats; D012165:Retinal Ganglion Cells / Q000473:pathology
chemical_list: D017077:Culture Media, Conditioned; D009414:Nerve Growth Factors
references: Cell Rep. 2012 Jun 28;1(6):703-14
references: 22813745
references: Methods Mol Biol. 2010;584:425-43
references: 19907991
references: Cell Transplant. 2012;21(5):827-43
references: 21944670
references: Invest Ophthalmol Vis Sci. 2010 Nov;51(11):5970-8
references: 20484577
references: Cell. 2007 Nov 30;131(5):861-72
references: 18035408
references: Stem Cells. 2006 Feb;24(2):246-57
references: 16123388
references: Invest Ophthalmol Vis Sci. 2008 Aug;49(8):3449-56
references: 18408183
references: Cytokine. 2003 May;22(3-4):101-6
references: 12849709
references: Stem Cells. 2006 Feb;24(2):274-83
references: 16123383
references: Semin Cell Dev Biol. 2004 Feb;15(1):115-23
references: 15036214
references: Eur J Neurosci. 1993 Jun 1;5(6):680-90
references: 8261140
references: Prog Retin Eye Res. 2012 Sep;31(5):351-76
references: 22561546
references: PLoS One. 2011 Apr 29;6(4):e18992
references: 21559507
references: Brain Res. 2010 Sep 10;1351:50-56
references: 20637745
references: Brain. 2006 Feb;129(Pt 2):490-502
references: 16339795
references: Science. 1998 Nov 6;282(5391):1145-7
references: 9804556
references: Exp Eye Res. 2008 Apr;86(4):601-11
references: 18294631
references: Invest Ophthalmol Vis Sci. 2010 Feb;51(2):960-70
references: 19850833
references: Stem Cells. 2010 Apr;28(4):695-703
references: 20166150
references: Stem Cells Dev. 2011 Mar;20(3):503-14
references: 20632795
references: Neurosci Lett. 2009 Jul 24;458(3):126-31
references: 19379795
references: J Exp Biol. 1946 May;22:221-4
references: 20988226
references: Cell Transplant. 2012;21(12):2587-602
references: 22889472
references: PLoS One. 2009 Dec 03;4(12):e8152
references: 19997644
references: Proc Natl Acad Sci U S A. 2009 Sep 29;106(39):16698-703
references: 19706890
references: Stem Cells. 2011 May;29(5):825-35
references: 21480547
references: Mol Cell Neurosci. 2000 Sep;16(3):197-205
references: 10995547
references: Ann Anat. 2002 Mar;184(2):113-23
references: 11936190
references: Biochem Biophys Res Commun. 2009 Mar 6;380(2):230-5
references: 19167364
references: Nature. 2006 Nov 9;444(7116):203-7
references: 17093405
references: Proc Natl Acad Sci U S A. 2009 Mar 3;106(9):3225-30
references: 19218428
references: Glia. 1996 Apr;16(4):351-8
references: 8721675
references: J Cell Biochem. 2008 Oct 15;105(3):633-40
references: 18759328
references: Stem Cell Res. 2012 Jan;8(1):120-33
references: 22099026
references: Stem Cell Rev Rep. 2010 Mar;6(1):96-107
references: 20012714
references: Nature. 2005 Jul 14;436(7048):266-71
references: 16015332
references: Curr Gene Ther. 2011 Apr;11(2):116-31
references: 21291357
references: Eur J Neurosci. 2002 Feb;15(4):637-43
references: 11886444
references: Neurosci Lett. 2001 Jun 8;305(2):139-42
references: 11376903
references: Proc Natl Acad Sci U S A. 2011 Oct 4;108(40):16825-30
references: 21949375
references: Exp Eye Res. 2007 Aug;85(2):234-41
references: 17570362
references: PLoS One. 2011;6(11):e27925
references: 22125639
references: PLoS One. 2010 Jan 20;5(1):e8763
references: 20098701
references: Ophthalmology. 1999 Jul;106(7):1268-77
references: 10406604
references: J Trauma Acute Care Surg. 2012 May;72(5):1350-5
references: 22673265
references: Neuropsychobiology. 1993;28(1-2):62-5
references: 8255411
references: Int J Dev Biol. 2010;54(5):877-86
references: 19876814