title: Osteopoietic engraftment after bone marrow transplantation: effect of inbred strain of mice.
abstract: OBJECTIVE
  Transplantable osteoprogenitors, as well as hematopoietic progenitors, reside in bone marrow. We previously reported the first clinical trial of bone marrow transplantation (BMT) for a genetic disorder of bone, osteogenesis imperfecta. Although the patients demonstrated striking clinical benefits after transplantation, measured osteopoietic engraftment was low and did not seem to be durable. Therefore, we sought an animal model, which closely reflects the clinical experience, to facilitate development of strategies to improve the efficiency of osteoprogenitor engraftment after BMT.
  
  
  METHODS
  We transplanted unfractionated bone marrow cells from green fluorescent protein-transgenic mice into lethally irradiated recipients in four combinations of inbred mouse strains: from C57BL/6 into C57BL/6 (C-C), from C57BL/6 into FVB/N (C-F), from FVB/N into C57BL/6 (F-C), and from FVB/N into FVB/N (F-F). At 2 weeks after transplantation, we assessed donor hematopoietic and osteopoietic engraftment by flow cytometry, using a novel mean fluorescence assay, and by immunohistochemical staining for green fluorescent protein.
  
  
  RESULTS
  Hematopoietic reconstitution by donor cells was complete in all four combinations. Although osteopoietic engraftment of the transplanted cells was also documented in all the four groups, the magnitude of osteopoietic engraftment differed markedly among the strains where F-F > C-F > F-C > C-C.
  
  
  CONCLUSIONS
  Our findings indicate that the genetic background of inbred mouse strains affects efficiency of osteopoietic engraftment after BMT. Thus, the murine strain must be considered when comparing experimental outcomes. Moreover, comparing the genetic variation among murine strains may lend insight into the factors governing osteopoietic differentiation of transplanted marrow cells.
authors.affiliation: Division of Oncology/Blood and Marrow Transplantation, The Children's Hospital of Philadelphia and The University of Pennsylvania School of Medicine, Philadelphia, Pa., USA.
authors.forename: Satoru
authors.initials: S
authors.lastname: Otsuru
authors.forename: Ted J
authors.initials: TJ
authors.lastname: Hofmann
authors.forename: Valeria
authors.initials: V
authors.lastname: Rasini
authors.forename: Elena
authors.initials: E
authors.lastname: Veronesi
authors.forename: Massimo
authors.initials: M
authors.lastname: Dominici
authors.forename: Edwin M
authors.initials: EM
authors.lastname: Horwitz
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D006412:Hematopoietic Stem Cells; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D010012:Osteogenesis; D013045:Species Specificity; D014184:Transplantation, Homologous
references.citation: Blood. 1998 Feb 1;91(3):756-63
references.pmid: 9446633
references.citation: Exp Hematol. 2008 Mar;36(3):360-8
references.pmid: 18179857
references.citation: Science. 1997 Apr 4;276(5309):71-4
references.pmid: 9082988
references.citation: In Vitro Cell Dev Biol Anim. 1994 Jun;30A(6):379-83
references.pmid: 8087303
references.citation: Blood. 2005 Nov 15;106(10):3650-7
references.pmid: 16081694
references.citation: Proc Natl Acad Sci U S A. 2004 Aug 10;101(32):11761-6
references.pmid: 15282377
references.citation: Blood. 1994 Oct 15;84(8):2497-505
references.pmid: 7522631
references.citation: Nat Med. 1999 Mar;5(3):309-13
references.pmid: 10086387
references.citation: Proc Natl Acad Sci U S A. 1995 May 23;92(11):4857-61
references.pmid: 7761413
references.citation: Bone. 2000 Jul;27(1):53-60
references.pmid: 10865209
references.citation: J Cell Biochem. 1999 Mar 15;72(4):570-85
references.pmid: 10022616
references.citation: Blood. 2009 Sep 10;114(11):2333-43
references.pmid: 19433859
references.citation: Bone Marrow Transplant. 2003 Oct;32(7):657-63
references.pmid: 13130312
references.citation: Bone. 1996 May;18(5):397-403
references.pmid: 8739896
references.citation: Blood. 2008 Apr 15;111(8):4386-91
references.pmid: 18182575
references.citation: Proc Natl Acad Sci U S A. 1998 Feb 3;95(3):1142-7
references.pmid: 9448299
references.citation: Blood. 2001 Mar 1;97(5):1227-31
references.pmid: 11222364
references.citation: Cytotherapy. 2006;8(4):315-7
references.pmid: 16923606
references.citation: Bone. 1998 Mar;22(3):211-6
references.pmid: 9514213
references.citation: J Bone Miner Res. 2003 Apr;18(4):624-36
references.pmid: 12674323
references.citation: J Bone Miner Res. 2009 Jun;24(6):1002-12
references.pmid: 19113913
references.citation: Exp Neurol. 2005 Sep;195(1):127-39
references.pmid: 15921683
references.citation: Genesis. 2005 May;42(1):17-22
references.pmid: 15828004
references.citation: J Clin Invest. 1990 Nov;86(5):1387-95
references.pmid: 2243119