Hematopoietic cells and osteoblasts are derived from a common marrow progenitor after bone marrow transplantation.
Bone and bone marrow are closely aligned physiologic compartments, suggesting that these tissues may represent a single functional unit with a common bone marrow progenitor that gives rise to both osteoblasts and hematopoietic cells. Although reports of multilineage engraftment by a single marrow-derived stem cell support this idea, more recent evidence has challenged claims of stem cell transdifferentiation and therefore the existence of a multipotent hematopoietic/osteogenic progenitor cell. Using a repopulation assay in mice, we show here that gene-marked, transplantable marrow cells from the plastic-nonadherent population can generate both functional osteoblasts/osteocytes and hematopoietic cells. Fluorescent in situ hybridization for the X and Y chromosomes and karyotype analysis of cultured osteoblasts confirmed the donor origin of these cells and excluded their generation by a fusion process. Molecular analysis demonstrated a common retroviral integration site in clonogenic hematopoietic cells and osteoprogenitors from each of seven animals studied, establishing a shared clonal origin for these ostensibly independent cell types. Our findings indicate that the bone marrow contains a primitive cell able to generate both the hematopoietic and osteocytic lineages. Its isolation and characterization may suggest novel treatments for genetic bone diseases and bone injuries.
Dominici
Massimo
M
Division of Experimental Hematology, St. Jude Children's Research Hospital, 332 North Lauderdale Street, Memphis, TN 38105, USA.
Pritchard
Colin
C
Garlits
John E
JE
Hofmann
Ted J
TJ
Persons
Derek A
DA
Horwitz
Edwin M
EM
D000818:Animals; D001773:Blood Cells / Q000166:cytology*; D001854:Bone Marrow Cells / Q000166:cytology*; D016026:Bone Marrow Transplantation; D001842:Bone and Bones / Q000166:cytology; D019070:Cell Lineage; D002999:Clone Cells; D006085:Graft Survival; D007621:Karyotyping; D051379:Mice; D008815:Mice, Inbred Strains; D039902:Multipotent Stem Cells / Q000166:cytology*; D010006:Osteoblasts / Q000166:cytology*; D010011:Osteocytes / Q000166:cytology