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.
Division of Experimental Hematology, St. Jude Children's Research Hospital, 332 North Lauderdale Street, Memphis, TN 38105, USA.
Massimo
M
Dominici
Colin
C
Pritchard
John E
JE
Garlits
Ted J
TJ
Hofmann
Derek A
DA
Persons
Edwin M
EM
Horwitz
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