title: Fate of amnion-derived stem cells transplanted to the fetal rat brain: migration, survival and differentiation.
abstract: We have recently characterized a stem cell population isolated from the rodent amniotic membrane termed amnion-derived stem cells (ADSCs). In vitro ADSCs differentiate into cell types representing all three embryonic layers, including neural cells. In this study we evaluated the neuroectodermal potential of ADSCs in vivo after in utero transplantation into the developing rat brain. A clonal line of green fluorescent protein-expressing ADSCs were infused into the telencephalic ventricles of the developing embryonic day 15.5 rat brain. At E17.5 donor cells existed primarily as spheres in the ventricles with subsets fused to the ventricular walls, suggesting a mode of entry into the brain parenchyma. By E21.5 green fluorescent protein (GFP) ADSCs migrated to a number of brain regions. Examination at postnatal time points revealed that donor ADSCs expressed vimentin and nestin. Subsets of transplanted ADSCs attained neuronal morphologies, although there was no immunohistochemical evidence of neural or glial differentiation. Some donor cells migrated around blood vessels and differentiated into putative endothelial cells. Donor ADSCs transplanted in utero were present in recipients into adulthood with no evidence of immunological rejection or tumour formation. Long-term survival may suggest utility in the treatment of disorders where differentiation to a neural cell type is not required for clinical benefit.
authors.affiliation: The Ira B. Black Center for Stem Cell Research and the Department of Neuroscience and Cell Biology, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway NJ 08854-5635, USA. marcusak@umdnj.edu
authors.forename: A J
authors.initials: AJ
authors.lastname: Marcus
authors.forename: T M
authors.initials: TM
authors.lastname: Coyne
authors.forename: I B
authors.initials: IB
authors.lastname: Black
authors.forename: D
authors.initials: D
authors.lastname: Woodbury
mesh_terms: D000650:Amnion / Q000166:cytology*; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000166:cytology*; D002454:Cell Differentiation; D002465:Cell Movement; D002470:Cell Survival; D004622:Embryo, Mammalian / Q000166:cytology; D005333:Fetus / Q000166:cytology*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D019579:Neocortex / Q000166:cytology; D009474:Neurons / Q000166:cytology; D010641:Phenotype; D051381:Rats; D017207:Rats, Sprague-Dawley; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology*; D013997:Time Factors
chemical_list: D049452:Green Fluorescent Proteins
references.citation: J Neurosci. 2006 Nov 29;26(48):12497-511
references.pmid: 17135412
references.citation: J Neurosci. 2004 May 12;24(19):4585-95
references.pmid: 15140930
references.citation: Neuron. 1995 Dec;15(6):1259-73
references.pmid: 8845151
references.citation: Blood. 2001 Mar 15;97(6):1625-34
references.pmid: 11238101
references.citation: Invest Ophthalmol Vis Sci. 2005 Mar;46(3):900-7
references.pmid: 15728546
references.citation: Neuron. 1995 Dec;15(6):1275-85
references.pmid: 8845152
references.citation: Biochem Biophys Res Commun. 2006 May 19;343(4):1045-52
references.pmid: 16574067
references.citation: Biochem Biophys Res Commun. 2007 Mar 16;354(3):700-6
references.pmid: 17257581
references.citation: Cell Transplant. 2002;11(3):265-74
references.pmid: 12075992
references.citation: Stem Cells. 2005;23(1):3-9
references.pmid: 15625118
references.citation: Neuroscience. 2006 Sep 29;142(1):287-304
references.pmid: 17120358
references.citation: J Exp Med. 2004 Jul 19;200(2):123-35
references.pmid: 15263023
references.citation: Proc Natl Acad Sci U S A. 1997 Dec 23;94(26):14809-14
references.pmid: 9405695
references.citation: Proc Natl Acad Sci U S A. 2006 Nov 14;103(46):17438-43
references.pmid: 17088535
references.citation: J Neurosurg. 2006 Aug;105(2 Suppl):127-33
references.pmid: 16922074
references.citation: Br J Haematol. 2000 Apr;109(1):235-42
references.pmid: 10848804
references.citation: Clin Pharmacol Ther. 2007 Sep;82(3):241-3
references.pmid: 17700588
references.citation: Differentiation. 2008 Feb;76(2):130-44
references.pmid: 17608732
references.citation: J Neuropathol Exp Neurol. 2005 Aug;64(8):681-8
references.pmid: 16106216
references.citation: Invest Ophthalmol Vis Sci. 2001 Jun;42(7):1539-46
references.pmid: 11381058
references.citation: J Clin Invest. 1982 Dec;70(6):1324-8
references.pmid: 7174797
references.citation: Blood. 1974 Mar;43(3):357-61
references.pmid: 4811820
references.citation: Proc Natl Acad Sci U S A. 2007 Jun 26;104(26):11002-7
references.pmid: 17569781
references.citation: Blood Cells Mol Dis. 2001 May-Jun;27(3):632-6
references.pmid: 11482877
references.citation: J Pediatr Surg. 2002 Jul;37(7):995-9; discussion 995-9
references.pmid: 12077757
references.citation: Stem Cells. 2003;21(2):181-9
references.pmid: 12634414
references.citation: Nat Neurosci. 2000 Jun;3(6):537-44
references.pmid: 10816308
references.citation: Proc Natl Acad Sci U S A. 2005 Dec 13;102(50):18171-6
references.pmid: 16330757
references.citation: Transplantation. 2005 Jun 15;79(11):1607-14
references.pmid: 15940052