title: Paracrine interaction between adipose-derived stromal cells and cranial suture-derived mesenchymal cells.
abstract: BACKGROUND
  Adipose-derived stromal cells are a potential cell source for the successful healing of skeletal defects. In this study, the authors sought to investigate the potential for cranial suture-derived mesenchymal cells to promote the osteogenic differentiation of adipose-derived stromal cells. Various reports have previously examined the unique in vitro attributes of suture-derived mesenchymal cells; this study sought to extend those findings.
  
  
  METHODS
  Suture-derived mesenchymal cells were isolated from wild-type mice (n = 30) from both fusing posterofrontal and patent sagittal sutures. Cells were placed in Transwell inserts with human adipose-derived stromal cells (n = 5 patients) with osteogenic differentiation medium with or without recombinant Noggin (10 to 400 ng/ml). Specific gene expression of osteogenic markers and Hedgehog pathway were assayed; standard osteogenic assays (alkaline phosphatase and alizarin red staining) were performed. All assays were performed in triplicate.
  
  
  RESULTS
  Both posterofrontal and sagittal suture-derived mesenchymal cells induced osteogenic differentiation of adipose-derived stromal cells (p < 0.05). Posterofrontal suture-derived mesenchymal cells induced adipose-derived stromal cell osteogenesis to a greater degree than sagittal suture-derived mesenchymal cells (p < 0.05). This was accompanied by an increase in bone morphogenetic protein expression (p < 0.05). Finally, recombinant Noggin mitigated the pro-osteogenic effects of co-culture accompanied by a reduction in Hedgehog signaling (p < 0.05).
  
  
  CONCLUSIONS
  Suture-derived mesenchymal cells secrete paracrine factors that induce osteogenic differentiation of multipotent stromal cells (human adipose-derived stromal cells). Cells derived from the fusing posterofrontal suture do this to a significantly greater degree than cells from the patent sagittal suture. Enhanced bone morphogenetic protein and Hedgehog signaling may underlie this paracrine effect.
authors.affiliation: Stanford, Calif. From the Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Plastic and Reconstructive Surgery Division, Stanford University School of Medicine.
authors.forename: Aaron W
authors.initials: AW
authors.lastname: James
authors.forename: Benjamin
authors.initials: B
authors.lastname: Levi
authors.forename: George W
authors.initials: GW
authors.lastname: Commons
authors.forename: Jason
authors.initials: J
authors.lastname: Glotzbach
authors.forename: Michael T
authors.initials: MT
authors.lastname: Longaker
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D002454:Cell Differentiation; D006801:Humans; D008648:Mesoderm / Q000166:cytology*; D051379:Mice; D010012:Osteogenesis; D019899:Paracrine Communication; D012886:Skull / Q000166:cytology; D017154:Stromal Cells / Q000166:cytology*; D013537:Sutures
references.citation: Bone. 2004 Feb;34(2):271-80
references.pmid: 14962805
references.citation: J Cell Physiol. 2002 Nov;193(2):225-32
references.pmid: 12385000
references.citation: J Bone Miner Res. 2000 Dec;15(12):2413-30
references.pmid: 11127206
references.citation: Ann Plast Surg. 2007 Feb;58(2):215-21
references.pmid: 17245153
references.citation: J Cell Sci. 2001 Jun;114(Pt 11):2085-94
references.pmid: 11493644
references.citation: Bone. 2008 Jun;42(6):1040-52
references.pmid: 18420480
references.citation: Curr Top Dev Biol. 2005;66:287-328
references.pmid: 15797457
references.citation: Cleft Palate Craniofac J. 1996 Mar;33(2):150-6
references.pmid: 8695623
references.citation: Plast Reconstr Surg. 2009 Jan;123(1):31-43
references.pmid: 19116522
references.citation: Stem Cells. 2005 Mar;23(3):412-23
references.pmid: 15749936
references.citation: J Bone Joint Surg Am. 2003;85-A Suppl 3:52-8
references.pmid: 12925610
references.citation: Bone. 2003 Jun;32(6):611-20
references.pmid: 12810168
references.citation: Bone. 2008 Feb;42(2):432-8
references.pmid: 18032124
references.citation: Ann Plast Surg. 2008 May;60(5):538-44
references.pmid: 18434829
references.citation: Plast Reconstr Surg. 1997 Oct;100(5):1091-9; discussion; 1100-2
references.pmid: 9326769
references.citation: J Biol Chem. 2004 Aug 27;279(35):36293-8
references.pmid: 15199066
references.citation: Cells Tissues Organs. 2004;178(1):2-12
references.pmid: 15550755
references.citation: Development. 1998 Apr;125(7):1241-51
references.pmid: 9477322
references.citation: Development. 2008 Sep;135(17):2845-54
references.pmid: 18653558
references.citation: Plast Reconstr Surg. 2002 Jun;109(7):2338-46; discussion 2347-54
references.pmid: 12045561
references.citation: Biochem Biophys Res Commun. 1997 Aug 18;237(2):465-9
references.pmid: 9268735
references.citation: Plast Reconstr Surg. 2010 Sep;126(3):822-834
references.pmid: 20811215
references.citation: Ann Plast Surg. 2008 Mar;60(3):306-22
references.pmid: 18443514
references.citation: Biochem Biophys Res Commun. 2002 Jun 7;294(2):371-9
references.pmid: 12051722
references.citation: Plast Reconstr Surg. 1998 Nov;102(6):1805-17; discussion 1818-20
references.pmid: 9810974
references.citation: Plast Reconstr Surg. 2008 Aug;122(2):389-399
references.pmid: 18626354
references.citation: Pflugers Arch. 2007 Mar;453(6):851-61
references.pmid: 17061120
references.citation: Plast Reconstr Surg. 2004 May;113(6):1685-97
references.pmid: 15114130
references.citation: Plast Reconstr Surg. 2002 Aug;110(2):506-14
references.pmid: 12142669
references.citation: Transfusion. 1996 Apr;36(4):303-8
references.pmid: 8623128
references.citation: Plast Reconstr Surg. 2007 Mar;119(3):819-29
references.pmid: 17312483
references.citation: Tissue Eng. 2006 Jul;12(7):2031-40
references.pmid: 16889531
references.citation: J Bone Miner Res. 1997 Mar;12(3):311-21
references.pmid: 9076573
references.citation: Tissue Eng Part A. 2009 Dec;15(12):3697-707
references.pmid: 19505250
references.citation: Plast Reconstr Surg. 2008 Jul;122(1):53-63
references.pmid: 18594386
references.citation: Bone. 2001 Jul;29(1):54-61
references.pmid: 11472891
references.citation: Plast Reconstr Surg. 2007 Dec;120(7):1783-1795
references.pmid: 18090740
references.citation: Am J Pathol. 2001 Feb;158(2):441-52
references.pmid: 11159182
references.citation: Plast Reconstr Surg. 2005 Oct;116(5):1353-62
references.pmid: 16217479
references.citation: Bone. 2003 Dec;33(6):899-910
references.pmid: 14678849
references.citation: Development. 2007 Sep;134(17):3133-44
references.pmid: 17670790
references.citation: J Clin Invest. 2003 Sep;112(6):924-34
references.pmid: 12975477
references.citation: Dev Dyn. 1993 Dec;198(4):312-22
references.pmid: 8130378
references.citation: J Tissue Eng Regen Med. 2010 Mar;4(3):224-32
references.pmid: 19967746
references.citation: Mol Biol Cell. 2002 Dec;13(12):4279-95
references.pmid: 12475952
references.citation: Arch Oral Biol. 2005 Mar;50(3):367-72
references.pmid: 15740717
references.citation: Plast Reconstr Surg. 1999 Jul;104(1):129-38
references.pmid: 10597685
references.citation: Plast Reconstr Surg. 1996 Apr;97(4):693-9
references.pmid: 8628762
references.citation: J Cell Physiol. 2006 Jan;206(1):229-37
references.pmid: 16021633
references.citation: Plast Reconstr Surg. 1999 Aug;104(2):435-44
references.pmid: 10654687
references.citation: Plast Reconstr Surg. 2002 Feb;109(2):645-54
references.pmid: 11818848
references.citation: Tissue Eng. 2007 Dec;13(12):2981-93
references.pmid: 17916040
references.citation: Plast Reconstr Surg. 2008 Dec;122(6):1649-1659
references.pmid: 19050517
references.citation: Tissue Eng Part A. 2010 Mar;16(3):917-31
references.pmid: 19824802
references.citation: Genes Dev. 1999 Aug 15;13(16):2072-86
references.pmid: 10465785
references.citation: Plast Reconstr Surg. 1998 May;101(6):1431-40
references.pmid: 9583470
references.citation: Ann Plast Surg. 1999 May;42(5):502-8
references.pmid: 10340858
references.citation: Nature. 2003 Apr 10;422(6932):625-9
references.pmid: 12687003
references.citation: Biochem Biophys Res Commun. 2005 Mar 18;328(3):651-7
references.pmid: 15694398
references.citation: Dev Biol. 2005 Apr 15;280(2):344-61
references.pmid: 15882577
references.citation: Plast Reconstr Surg. 1998 May;101(6):1441-7
references.pmid: 9583471
references.citation: PLoS One. 2009 Sep 22;4(9):e7120
references.pmid: 19771170
references.citation: J Craniofac Surg. 2003 May;14(3):363-70
references.pmid: 12826808
references.citation: Plast Reconstr Surg. 2004 Dec;114(7):1818-25
references.pmid: 15577353
references.citation: Plast Reconstr Surg. 2002 Feb;109(2):631-42; discussion 643-4
references.pmid: 11818846
references.citation: Dev Biol. 2002 Jan 1;241(1):106-16
references.pmid: 11784098
references.citation: Curr Opin Mol Ther. 2005 Aug;7(4):300-5
references.pmid: 16121695
references.citation: J Cell Physiol. 2001 Oct;189(1):54-63
references.pmid: 11573204
references.citation: Gene Ther. 2005 Jan;12(1):75-86
references.pmid: 15510177