Stem/progenitor cells from inflamed human dental pulp retain tissue regeneration potential.
BACKGROUND
Potent stem/progenitor cells have been isolated from normal human dental pulps termed dental pulp stem cells (DPSCs). However, it is unknown whether these cells exist in inflamed pulps (IPs).


OBJECTIVE
To determine whether DPSCs can be identified and isolated from IPs; and if they can be successfully cultured, whether they retain tissue regeneration potential in vivo.


METHODS
DPSCs from freshly collected normal pulps (NPs) and IPs were characterized in vitro and their tissue regeneration potential tested using an in vivo study model.


RESULTS
The immunohistochemical analysis showed that IPs expressed higher levels of mesenchymal stem cell markers STRO-1, CD90, CD105 and CD146 compared with NPs (p < 0.05). Flow cytometry analysis showed that DPSCs from both NPs and IPs expressed moderate to high levels of CD146, stage-specific embryonic antigen-4, CD73 and CD166. Total population doubling of DPSCs-IPs (44.6 + or - 2.9) was lower than that of DPSCs-NPs (58.9 + or - 2.5) (p < 0.05), and DPSCs-IPs appeared to have a decreased osteo/dentinogenic potential compared with DPSCs-NPs based on the mineral deposition in cultures. Nonetheless, DPSCs-IPs formed pulp/dentin complexes similar to DPSCs-NPs when transplanted into immunocompromised mice.


CONCLUSIONS
DPSCs-IPs can be isolated and their mesenchymal stem cell marker profiles are similar to those from NPs. Although some stem cell properties of DPSCs-IPs were altered, cells from some samples remained potent in tissue regeneration in vivo.
Alongi
Dominick J
DJ
University of Maryland, College of Dental Surgery, MD, USA; and Boston University School of Dental Medicine, Department of Endodontics, Boston, MA 02118, USA.
Yamaza
Takayoshi
T
Song
Yingjie
Y
Fouad
Ashraf F
AF
Romberg
Elaine E
EE
Shi
Songtao
S
Tuan
Rocky S
RS
Huang
George T-J
GT
D000293:Adolescent; D000328:Adult; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D002454:Cell Differentiation; D049109:Cell Proliferation; D003782:Dental Pulp / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D007124:Immunoenzyme Techniques; D007249:Inflammation / Q000378:metabolism / Q000473:pathology*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics; D012038:Regeneration; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D023822:Tissue Engineering; D055815:Young Adult
D015415:Biomarkers; D012333:RNA, Messenger
J Dent Res. 2002 Aug;81(8):531-5
12147742
J Endod. 2008 Feb;34(2):166-71
18215674
J Oral Pathol Med. 2008 Oct;37(9):571-4
18331285
Mediators Inflamm. 2007;2007:69416
18320014
J Dent Res. 2009 Apr;88(4):339-44
19407154
J Cell Mol Med. 2008 Dec;12(6B):2552-65
19210755
J Appl Oral Sci. 2009 Sep-Oct;17(5):527-32
19936537
Stem Cells. 2006 Jul;24(7):1707-18
16574750
Hum Gene Ther. 2004 Nov;15(11):1045-53
15610605
Proc Natl Acad Sci U S A. 2006 Nov 14;103(46):17432-7
17088540
PLoS One. 2006 Dec 20;1:e79
17183711
Regen Med. 2009 Sep;4(5):697-707
19761395
J Endod. 2006 Nov;32(11):1066-73
17055908
J Endod. 2005 Oct;31(10):711-8
16186748
Cytokine. 2003 Apr;22(1-2):33-41
12946103
Biochem Biophys Res Commun. 2002 Aug 9;296(1):93-101
12147232
Histol Histopathol. 2009 Mar;24(3):347-66
19130405
J Am Coll Cardiol. 2009 Jan 27;53(4):305-8
19161877
J Bone Miner Res. 2003 Apr;18(4):696-704
12674330
Blood. 2009 Mar 12;113(11):2595-604
19074727
Transplantation. 2009 May 15;87(9 Suppl):S45-9
19424005
Tissue Eng Part A. 2010 Feb;16(2):605-15
19737072
Int Endod J. 2009 Oct;42(10):855-66
19549154
J Endod. 2008 Jun;34(6):645-51
18498881
Proc Natl Acad Sci U S A. 2003 May 13;100(10):5807-12
12716973
Cell Tissue Res. 2006 May;324(2):225-36
16440193
J Endod. 2004 Oct;30(10):704-7
15448463
Cytotherapy. 2006;8(4):315-7
16923606
J Dent Res. 2005 Nov;84(11):994-8
16246929
J Endod. 2006 Sep;32(9):853-61
16934628
J Cell Biochem. 2009 Oct 15;108(3):577-88
19650110
Front Biosci (Landmark Ed). 2009 Jan 01;14:4281-98
19273350
Endocrinology. 2000 Nov;141(11):3956-64
11089525
Proc Natl Acad Sci U S A. 2000 Dec 5;97(25):13625-30
11087820
Arthritis Res Ther. 2007;9(1):204
17316462
J Dent Res. 2009 Sep;88(9):792-806
19767575
J Cell Mol Med. 2004 Jul-Sep;8(3):301-16
15491506
Immunol Cell Biol. 2006 Oct;84(5):413-21
16869941
Arch Med Res. 2002 Sep-Oct;33(5):482-4
12459320