Primitive adult hematopoietic stem cells can function as osteoblast precursors

Elizabeth A. Olmsted-Davis, Zbigniew Gugala, Fernando Camargo, Francis H. Gannon, KathyJo Jackson, Kirsten Anderson Kienstra, H. David Shine, Ronald Lindsey, Karen K. Hirschi, Margaret A. Goodell, Malcolm K. Brenner, Alan R. Davis

Research output: Contribution to journalArticle

138 Citations (Scopus)

Abstract

Osteoblasts are continually recruited from stem cell pools to maintain bone. Although their immediate precursor is a plastic-adherent mesenchymal stem cell able to generate tissues other than bone, increasing evidence suggests the existence of a more primitive cell that can differentiate to both hematopoietic and mesenchymal cells. We show here that the "side population" (SP) of marrow stem cells, defined by their ability to rapidly expel a DNA-binding dye and to regenerate the hematopoietic compartment, can differentiate to osteoblasts through a mesenchymal intermediate. When transplanted into lethally irradiated mice, single gene-marked murine SP cells reconstituted depleted osteoprogenitor pools, such that a large proportion of the osteogenic cells in the epiphysis of long bone carried the donor SP cell marker. These findings suggest that the developmental capacity of SP cells is not restricted to the hematopoietic lineages but extends to osteogenic differentiation. This property not only elucidates a previously unrecognized step in osteoblast development, but also has intriguing implications for the use of SP cells in clinical orthopedics and stem cell-based disorders of bone.

Original languageEnglish (US)
Pages (from-to)15877-15882
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue number26
DOIs
StatePublished - Dec 23 2003
Externally publishedYes

Fingerprint

Side-Population Cells
Adult Stem Cells
Hematopoietic Stem Cells
Osteoblasts
Bone and Bones
Stem Cells
Epiphyses
Mesenchymal Stromal Cells
Plastics
Orthopedics
Coloring Agents
Bone Marrow
DNA
Population
Genes

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Primitive adult hematopoietic stem cells can function as osteoblast precursors. / Olmsted-Davis, Elizabeth A.; Gugala, Zbigniew; Camargo, Fernando; Gannon, Francis H.; Jackson, KathyJo; Kienstra, Kirsten Anderson; Shine, H. David; Lindsey, Ronald; Hirschi, Karen K.; Goodell, Margaret A.; Brenner, Malcolm K.; Davis, Alan R.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 100, No. 26, 23.12.2003, p. 15877-15882.

Research output: Contribution to journalArticle

Olmsted-Davis, EA, Gugala, Z, Camargo, F, Gannon, FH, Jackson, K, Kienstra, KA, Shine, HD, Lindsey, R, Hirschi, KK, Goodell, MA, Brenner, MK & Davis, AR 2003, 'Primitive adult hematopoietic stem cells can function as osteoblast precursors', Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 26, pp. 15877-15882. https://doi.org/10.1073/pnas.2632959100
Olmsted-Davis, Elizabeth A. ; Gugala, Zbigniew ; Camargo, Fernando ; Gannon, Francis H. ; Jackson, KathyJo ; Kienstra, Kirsten Anderson ; Shine, H. David ; Lindsey, Ronald ; Hirschi, Karen K. ; Goodell, Margaret A. ; Brenner, Malcolm K. ; Davis, Alan R. / Primitive adult hematopoietic stem cells can function as osteoblast precursors. In: Proceedings of the National Academy of Sciences of the United States of America. 2003 ; Vol. 100, No. 26. pp. 15877-15882.
@article{87e552665ed048b7af05056dd3a2287e,
title = "Primitive adult hematopoietic stem cells can function as osteoblast precursors",
abstract = "Osteoblasts are continually recruited from stem cell pools to maintain bone. Although their immediate precursor is a plastic-adherent mesenchymal stem cell able to generate tissues other than bone, increasing evidence suggests the existence of a more primitive cell that can differentiate to both hematopoietic and mesenchymal cells. We show here that the {"}side population{"} (SP) of marrow stem cells, defined by their ability to rapidly expel a DNA-binding dye and to regenerate the hematopoietic compartment, can differentiate to osteoblasts through a mesenchymal intermediate. When transplanted into lethally irradiated mice, single gene-marked murine SP cells reconstituted depleted osteoprogenitor pools, such that a large proportion of the osteogenic cells in the epiphysis of long bone carried the donor SP cell marker. These findings suggest that the developmental capacity of SP cells is not restricted to the hematopoietic lineages but extends to osteogenic differentiation. This property not only elucidates a previously unrecognized step in osteoblast development, but also has intriguing implications for the use of SP cells in clinical orthopedics and stem cell-based disorders of bone.",
author = "Olmsted-Davis, {Elizabeth A.} and Zbigniew Gugala and Fernando Camargo and Gannon, {Francis H.} and KathyJo Jackson and Kienstra, {Kirsten Anderson} and Shine, {H. David} and Ronald Lindsey and Hirschi, {Karen K.} and Goodell, {Margaret A.} and Brenner, {Malcolm K.} and Davis, {Alan R.}",
year = "2003",
month = "12",
day = "23",
doi = "10.1073/pnas.2632959100",
language = "English (US)",
volume = "100",
pages = "15877--15882",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "26",

}

TY - JOUR

T1 - Primitive adult hematopoietic stem cells can function as osteoblast precursors

AU - Olmsted-Davis, Elizabeth A.

AU - Gugala, Zbigniew

AU - Camargo, Fernando

AU - Gannon, Francis H.

AU - Jackson, KathyJo

AU - Kienstra, Kirsten Anderson

AU - Shine, H. David

AU - Lindsey, Ronald

AU - Hirschi, Karen K.

AU - Goodell, Margaret A.

AU - Brenner, Malcolm K.

AU - Davis, Alan R.

PY - 2003/12/23

Y1 - 2003/12/23

N2 - Osteoblasts are continually recruited from stem cell pools to maintain bone. Although their immediate precursor is a plastic-adherent mesenchymal stem cell able to generate tissues other than bone, increasing evidence suggests the existence of a more primitive cell that can differentiate to both hematopoietic and mesenchymal cells. We show here that the "side population" (SP) of marrow stem cells, defined by their ability to rapidly expel a DNA-binding dye and to regenerate the hematopoietic compartment, can differentiate to osteoblasts through a mesenchymal intermediate. When transplanted into lethally irradiated mice, single gene-marked murine SP cells reconstituted depleted osteoprogenitor pools, such that a large proportion of the osteogenic cells in the epiphysis of long bone carried the donor SP cell marker. These findings suggest that the developmental capacity of SP cells is not restricted to the hematopoietic lineages but extends to osteogenic differentiation. This property not only elucidates a previously unrecognized step in osteoblast development, but also has intriguing implications for the use of SP cells in clinical orthopedics and stem cell-based disorders of bone.

AB - Osteoblasts are continually recruited from stem cell pools to maintain bone. Although their immediate precursor is a plastic-adherent mesenchymal stem cell able to generate tissues other than bone, increasing evidence suggests the existence of a more primitive cell that can differentiate to both hematopoietic and mesenchymal cells. We show here that the "side population" (SP) of marrow stem cells, defined by their ability to rapidly expel a DNA-binding dye and to regenerate the hematopoietic compartment, can differentiate to osteoblasts through a mesenchymal intermediate. When transplanted into lethally irradiated mice, single gene-marked murine SP cells reconstituted depleted osteoprogenitor pools, such that a large proportion of the osteogenic cells in the epiphysis of long bone carried the donor SP cell marker. These findings suggest that the developmental capacity of SP cells is not restricted to the hematopoietic lineages but extends to osteogenic differentiation. This property not only elucidates a previously unrecognized step in osteoblast development, but also has intriguing implications for the use of SP cells in clinical orthopedics and stem cell-based disorders of bone.

UR - http://www.scopus.com/inward/record.url?scp=9144269969&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=9144269969&partnerID=8YFLogxK

U2 - 10.1073/pnas.2632959100

DO - 10.1073/pnas.2632959100

M3 - Article

VL - 100

SP - 15877

EP - 15882

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 26

ER -