Osteopoietic engraftment after bone marrow transplantation: effect of inbred strain of mice.
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.
Otsuru
Satoru
S
Division of Oncology/Blood and Marrow Transplantation, The Children's Hospital of Philadelphia and The University of Pennsylvania School of Medicine, Philadelphia, Pa., USA.
Hofmann
Ted J
TJ
Rasini
Valeria
V
Veronesi
Elena
E
Dominici
Massimo
M
Horwitz
Edwin M
EM
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
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