title: Isolation and characterization of neural crest-derived stem cells from dental pulp of neonatal mice.
abstract: Dental pulp stem cells (DPSCs) are shown to reside within the tooth and play an important role in dentin regeneration. DPSCs were first isolated and characterized from human teeth and most studies have focused on using this adult stem cell for clinical applications. However, mouse DPSCs have not been well characterized and their origin(s) have not yet been elucidated. Herein we examined if murine DPSCs are neural crest derived and determined their in vitro and in vivo capacity. DPSCs from neonatal murine tooth pulp expressed embryonic stem cell and neural crest related genes, but lacked expression of mesodermal genes. Cells isolated from the Wnt1-Cre/R26R-LacZ model, a reporter of neural crest-derived tissues, indicated that DPSCs were Wnt1-marked and therefore of neural crest origin. Clonal DPSCs showed multi-differentiation in neural crest lineage for odontoblasts, chondrocytes, adipocytes, neurons, and smooth muscles. Following in vivo subcutaneous transplantation with hydroxyapatite/tricalcium phosphate, based on tissue/cell morphology and specific antibody staining, the clones differentiated into odontoblast-like cells and produced dentin-like structure. Conversely, bone marrow stromal cells (BMSCs) gave rise to osteoblast-like cells and generated bone-like structure. Interestingly, the capillary distribution in the DPSC transplants showed close proximity to odontoblasts whereas in the BMSC transplants bone condensations were distant to capillaries resembling dentinogenesis in the former vs. osteogenesis in the latter. Thus we demonstrate the existence of neural crest-derived DPSCs with differentiation capacity into cranial mesenchymal tissues and other neural crest-derived tissues. In turn, DPSCs hold promise as a source for regenerating cranial mesenchyme and other neural crest derived tissues.
authors.affiliation: Department of Oral Health Sciences, School of Dentistry, University of Washington, Seattle, Washington, United States of America.
authors.forename: Kajohnkiart
authors.initials: K
authors.lastname: Janebodin
authors.forename: Orapin V
authors.initials: OV
authors.lastname: Horst
authors.forename: Nicholas
authors.initials: N
authors.lastname: Ieronimakis
authors.forename: Gayathri
authors.initials: G
authors.lastname: Balasundaram
authors.forename: Kanit
authors.initials: K
authors.lastname: Reesukumal
authors.forename: Busadee
authors.initials: B
authors.lastname: Pratumvinit
authors.forename: Morayma
authors.initials: M
authors.lastname: Reyes
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D019070:Cell Lineage; D003782:Dental Pulp / Q000166:cytology*; D053595:Embryonic Stem Cells / Q000166:cytology; D059630:Mesenchymal Stem Cells; D051379:Mice; D009432:Neural Crest / Q000166:cytology*; D013234:Stem Cells / Q000166:cytology*
references.citation: J Investig Dermatol Symp Proc. 2001 Nov;6(1):1-5
references.pmid: 11764276
references.citation: Cell Death Differ. 2007 Jun;14(6):1162-71
references.pmid: 17347663
references.citation: J Anat. 2005 Dec;207(6):687-93
references.pmid: 16367796
references.citation: Cell Tissue Res. 2003 Mar;311(3):393-9
references.pmid: 12658447
references.citation: Proc Natl Acad Sci U S A. 2000 Dec 5;97(25):13625-30
references.pmid: 11087820
references.citation: Int J Paediatr Dent. 2009 Jan;19(1):61-70
references.pmid: 19120509
references.citation: J Histochem Cytochem. 1997 Jun;45(6):883-93
references.pmid: 9199674
references.citation: Neuron. 2002 Aug 15;35(4):657-69
references.pmid: 12194866
references.citation: J Dent Res. 2002 Aug;81(8):531-5
references.pmid: 12147742
references.citation: PLoS One. 2009;4(5):e5435
references.pmid: 19415111
references.citation: Exp Cell Res. 1998 Jan 10;238(1):265-72
references.pmid: 9457080
references.citation: Development. 1997 Jan;124(2):505-14
references.pmid: 9053326
references.citation: Stem Cells. 2010 Aug;28(8):1435-45
references.pmid: 20572012
references.citation: J Neurobiol. 1997 Jun 20;32(7):722-46
references.pmid: 9183749
references.citation: Arch Oral Biol. 2001 Mar;46(3):221-8
references.pmid: 11165568
references.citation: Development. 1993 Feb;117(2):769-78
references.pmid: 8101169
references.citation: Cell. 1997 May 30;89(5):747-54
references.pmid: 9182762
references.citation: Cell. 1999 Mar 5;96(5):737-49
references.pmid: 10089888
references.citation: J Bone Miner Res. 2003 Apr;18(4):696-704
references.pmid: 12674330
references.citation: Exp Hematol. 2006 Nov;34(11):1596-601
references.pmid: 17046581
references.citation: Exp Hematol. 1976 Sep;4(5):267-74
references.pmid: 976387
references.citation: J Clin Invest. 2006 Dec;116(12):3139-49
references.pmid: 17099777
references.citation: Genesis. 2000 Oct;28(2):75-81
references.pmid: 11064424
references.citation: Development. 2003 Oct;130(19):4567-79
references.pmid: 12925584
references.citation: Cell. 2005 Sep 23;122(6):947-56
references.pmid: 16153702
references.citation: Dev Biol. 2003 Feb 1;254(1):131-48
references.pmid: 12606287
references.citation: Bone. 2002 Feb;30(2):377-85
references.pmid: 11856645
references.citation: Biol Cell. 2007 Aug;99(8):465-74
references.pmid: 17371295
references.citation: Stem Cell Rev. 2008 Dec;4(4):256-60
references.pmid: 18712509
references.citation: J Biol Chem. 2010 Mar 19;285(12):9180-9
references.pmid: 20071344
references.citation: Cells Tissues Organs. 2009;189(1-4):268-74
references.pmid: 18701814
references.citation: Biotechnol Prog. 2009 Jan-Feb;25(1):32-42
references.pmid: 19198002
references.citation: Stem Cells. 2007 Nov;25(11):2739-49
references.pmid: 17656645
references.citation: J Exp Zool B Mol Dev Evol. 2005 Jul 15;304(4):298-303
references.pmid: 15880502
references.citation: Tissue Eng. 2005 Mar-Apr;11(3-4):357-68
references.pmid: 15869416
references.citation: Arterioscler Thromb Vasc Biol. 2009 Oct;29(10):1644-50
references.pmid: 19608972
references.citation: Oral Dis. 2007 Mar;13(2):151-7
references.pmid: 17305615
references.citation: Stem Cells Dev. 2008 Dec;17(6):1175-84
references.pmid: 18393638
references.citation: Exp Biol Med (Maywood). 2001 Dec;226(11):997-1002
references.pmid: 11743135
references.citation: J Cell Biol. 2005 Sep 26;170(7):1135-46
references.pmid: 16186259
references.citation: Orthod Craniofac Res. 2005 Aug;8(3):191-9
references.pmid: 16022721
references.citation: Int J Immunopathol Pharmacol. 2009 Jul-Sep;22(3):699-706
references.pmid: 19822086
references.citation: Aust Endod J. 2003 Apr;29(1):5-12
references.pmid: 12772964
references.citation: Blood. 2005 Nov 15;106(10):3646-9
references.pmid: 16099880
references.citation: Blood. 1994 Dec 15;84(12):4164-73
references.pmid: 7994030
references.citation: Genes Dev. 1997 Jul 15;11(14):1827-39
references.pmid: 9242490
references.citation: Eur J Oral Sci. 2005 Aug;113(4):312-7
references.pmid: 16048523
references.citation: Proc Natl Acad Sci U S A. 2005 Apr 12;102(15):5530-4
references.pmid: 15802470
references.citation: J Cell Biochem. 2000 Jun 6;78(3):391-403
references.pmid: 10861838
references.citation: Nature. 1989 Jul 13;340(6229):167-8
references.pmid: 2662017
references.citation: Mol Cell Biol. 1997 Apr;17(4):2336-46
references.pmid: 9121483
references.citation: J Biol Chem. 2009 Jun 19;284(25):17293-17303
references.pmid: 19386589
references.citation: Proc Natl Acad Sci U S A. 2003 Jun 10;100(12):7129-34
references.pmid: 12756293
references.citation: Exp Cell Res. 2006 Jan 1;312(1):63-72
references.pmid: 16256983
references.citation: Cell Stem Cell. 2008 Sep 11;3(3):301-13
references.pmid: 18786417
references.citation: J Dent Res. 2003 Oct;82(10):776-80
references.pmid: 14514755
references.citation: Bone. 1996 Oct;19(4):371-80
references.pmid: 8894143
references.citation: J Cell Sci. 2003 May 1;116(Pt 9):1647-8
references.pmid: 12665545
references.citation: Immunity. 2006 Dec;25(6):862-4
references.pmid: 17174928
references.citation: J Cell Biol. 2005 Nov 7;171(3):483-92
references.pmid: 16275752
references.citation: J Cell Physiol. 2006 Jan;206(1):229-37
references.pmid: 16021633
references.citation: J Cell Mol Med. 2012 Apr;16(4):740-51
references.pmid: 21645238
references.citation: Development. 1993 Jun;118(2):463-75
references.pmid: 8223273
references.citation: Histochem J. 2000 Apr;32(4):239-45
references.pmid: 10872889
references.citation: Development. 2000 Apr;127(8):1671-9
references.pmid: 10725243
references.citation: Acta Anat (Basel). 1995;154(1):63-78
references.pmid: 8714290
references.citation: Cell. 2002 Jan 11;108(1):17-29
references.pmid: 11792318
references.citation: Biol Cell. 2006 Oct;98(10):567-75
references.pmid: 16719840
references.citation: Nature. 1991 Sep 26;353(6342):348-51
references.pmid: 1922339
references.citation: Proc Natl Acad Sci U S A. 2003 Sep 30;100 Suppl 1:11854-60
references.pmid: 12925733
references.citation: Int J Dev Biol. 2003 May;47(4):281-92
references.pmid: 12755333
references.citation: Anat Rec. 1996 Jun;245(2):313-26
references.pmid: 8769670
references.citation: Transgenic Res. 2006 Feb;15(1):101-6
references.pmid: 16475014
references.citation: J Anat. 1989 Oct;166:55-65
references.pmid: 2482839
references.citation: Stem Cells Dev. 2010 Jul;19(7):1055-65
references.pmid: 20102260
references.citation: Cell. 2007 Nov 30;131(5):861-72
references.pmid: 18035408
references.citation: J Bone Miner Metab. 2000;18(3):132-9
references.pmid: 10783846
references.citation: Stem Cells. 2007 Jan;25(1):156-64
references.pmid: 17204606
references.citation: J Endod. 2006 Nov;32(11):1066-73
references.pmid: 17055908
references.citation: Bone. 2010 Jun;46(6):1639-51
references.pmid: 20193787
references.citation: Tissue Cell. 2003 Feb;35(1):69-77
references.pmid: 12589731
references.citation: Cell Stem Cell. 2008 Sep 11;3(3):279-88
references.pmid: 18786415
references.citation: Biol Cell. 2003 Mar-Apr;95(2):75-86
references.pmid: 12799063
references.citation: FASEB J. 2000 Oct;14(13):2087-96
references.pmid: 11023993