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. MATERIALS AND 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. CONCLUSION: 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.
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. MATERIALS AND 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. CONCLUSION: 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: Massimo Dominici; Colin Pritchard; John E Garlits; Ted J Hofmann; Derek A Persons; Edwin M Horwitz Journal: Proc Natl Acad Sci U S A Date: 2004-07-28 Impact factor: 11.205
Authors: Michael P Whyte; Joanne Kurtzberg; William H McAlister; Steven Mumm; Michelle N Podgornik; Stephen P Coburn; Lawrence M Ryan; Cindy R Miller; Gary S Gottesman; Alan K Smith; Judy Douville; Barbara Waters-Pick; R Douglas Armstrong; Paul L Martin Journal: J Bone Miner Res Date: 2003-04 Impact factor: 6.741
Authors: R F Pereira; K W Halford; M D O'Hara; D B Leeper; B P Sokolov; M D Pollard; O Bagasra; D J Prockop Journal: Proc Natl Acad Sci U S A Date: 1995-05-23 Impact factor: 11.205
Authors: G J A Driessen; E J A Gerritsen; A Fischer; A Fasth; W C J Hop; P Veys; F Porta; A Cant; C G Steward; J M Vossen; D Uckan; W Friedrich Journal: Bone Marrow Transplant Date: 2003-10 Impact factor: 5.483
Authors: B P Chen; A Galy; S Kyoizumi; R Namikawa; J Scarborough; S Webb; B Ford; D Z Cen; S C Chen Journal: Blood Date: 1994-10-15 Impact factor: 22.113
Authors: Bruno L Lima; Enrico J C Santos; Gustavo R Fernandes; Christian Merkel; Marco R B Mello; Juliana P A Gomes; Marina Soukoyan; Alexandre Kerkis; Silvia M G Massironi; José A Visintin; Lygia V Pereira Journal: PLoS One Date: 2010-11-30 Impact factor: 3.240