CD146 expression on primary nonhematopoietic bone marrow stem cells is correlated with in situ localization

Ariane Tormin, Ou Li, Jan Claas Brune, Stuart Walsh, Birgit Schütz, Mats Ehinger, Nicholas Ditzel, Moustapha Kassem, Stefan Scheding

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Nonhematopoietic bone marrow mesenchymal stem cells (BM-MSCs) are of central importance for bone marrow stroma and the hematopoietic environment. However, the exact phenotype and anatomical distribution of specified MSC populations in the marrow are unknown. We characterized the phenotype of primary human BM-MSCs and found that all assayable colony-forming units-fibroblast (CFU-Fs) were highly and exclusively enriched not only in the lin⁻/CD271⁺/CD45⁻/CD146⁺ stem-cell fraction, but also in lin⁻/CD271⁺/CD45⁻/CD146(⁻/low) cells. Both populations, regardless of CD146 expression, shared a similar phenotype and genotype, gave rise to typical cultured stromal cells, and formed bone and hematopoietic stroma in vivo. Interestingly, CD146 was up-regulated in normoxia and down-regulated in hypoxia. This was correlated with in situ localization differences, with CD146 coexpressing reticular cells located in perivascular regions, whereas bone-lining MSCs expressed CD271 alone. In both regions, CD34⁺ hematopoietic stem/progenitor cells were located in close proximity to MSCs. These novel findings show that the expression of CD146 differentiates between perivascular versus endosteal localization of non-hematopoietic BM-MSC populations, which may be useful for the study of the hematopoietic environment.
OriginalsprogEngelsk
TidsskriftBlood
Vol/bind117
Udgave nummer19
Sider (fra-til)5067-77
Antal sider11
ISSN0006-4971
DOI
StatusUdgivet - 2011

Fingeraftryk

Mesenchymal Stromal Cells
Population
Stromal Cells
Cultured Cells
Fibroblasts
Adapalene

Citer dette

Tormin, A., Li, O., Brune, J. C., Walsh, S., Schütz, B., Ehinger, M., ... Scheding, S. (2011). CD146 expression on primary nonhematopoietic bone marrow stem cells is correlated with in situ localization. Blood, 117(19), 5067-77. https://doi.org/10.1182/blood-2010-08-304287
Tormin, Ariane ; Li, Ou ; Brune, Jan Claas ; Walsh, Stuart ; Schütz, Birgit ; Ehinger, Mats ; Ditzel, Nicholas ; Kassem, Moustapha ; Scheding, Stefan. / CD146 expression on primary nonhematopoietic bone marrow stem cells is correlated with in situ localization. I: Blood. 2011 ; Bind 117, Nr. 19. s. 5067-77.
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title = "CD146 expression on primary nonhematopoietic bone marrow stem cells is correlated with in situ localization",
abstract = "Nonhematopoietic bone marrow mesenchymal stem cells (BM-MSCs) are of central importance for bone marrow stroma and the hematopoietic environment. However, the exact phenotype and anatomical distribution of specified MSC populations in the marrow are unknown. We characterized the phenotype of primary human BM-MSCs and found that all assayable colony-forming units-fibroblast (CFU-Fs) were highly and exclusively enriched not only in the lin⁻/CD271⁺/CD45⁻/CD146⁺ stem-cell fraction, but also in lin⁻/CD271⁺/CD45⁻/CD146(⁻/low) cells. Both populations, regardless of CD146 expression, shared a similar phenotype and genotype, gave rise to typical cultured stromal cells, and formed bone and hematopoietic stroma in vivo. Interestingly, CD146 was up-regulated in normoxia and down-regulated in hypoxia. This was correlated with in situ localization differences, with CD146 coexpressing reticular cells located in perivascular regions, whereas bone-lining MSCs expressed CD271 alone. In both regions, CD34⁺ hematopoietic stem/progenitor cells were located in close proximity to MSCs. These novel findings show that the expression of CD146 differentiates between perivascular versus endosteal localization of non-hematopoietic BM-MSC populations, which may be useful for the study of the hematopoietic environment.",
keywords = "Animals, Antigens, CD146, Bone Marrow Cells, Cell Differentiation, Cell Separation, Cells, Cultured, Female, Flow Cytometry, Fluorescent Antibody Technique, Humans, Mesenchymal Stem Cells, Mice, Mice, Inbred NOD, Phenotype, Polymerase Chain Reaction, Transplantation, Heterologous",
author = "Ariane Tormin and Ou Li and Brune, {Jan Claas} and Stuart Walsh and Birgit Sch{\"u}tz and Mats Ehinger and Nicholas Ditzel and Moustapha Kassem and Stefan Scheding",
year = "2011",
doi = "10.1182/blood-2010-08-304287",
language = "English",
volume = "117",
pages = "5067--77",
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issn = "0006-4971",
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CD146 expression on primary nonhematopoietic bone marrow stem cells is correlated with in situ localization. / Tormin, Ariane; Li, Ou; Brune, Jan Claas; Walsh, Stuart; Schütz, Birgit; Ehinger, Mats; Ditzel, Nicholas; Kassem, Moustapha; Scheding, Stefan.

I: Blood, Bind 117, Nr. 19, 2011, s. 5067-77.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - CD146 expression on primary nonhematopoietic bone marrow stem cells is correlated with in situ localization

AU - Tormin, Ariane

AU - Li, Ou

AU - Brune, Jan Claas

AU - Walsh, Stuart

AU - Schütz, Birgit

AU - Ehinger, Mats

AU - Ditzel, Nicholas

AU - Kassem, Moustapha

AU - Scheding, Stefan

PY - 2011

Y1 - 2011

N2 - Nonhematopoietic bone marrow mesenchymal stem cells (BM-MSCs) are of central importance for bone marrow stroma and the hematopoietic environment. However, the exact phenotype and anatomical distribution of specified MSC populations in the marrow are unknown. We characterized the phenotype of primary human BM-MSCs and found that all assayable colony-forming units-fibroblast (CFU-Fs) were highly and exclusively enriched not only in the lin⁻/CD271⁺/CD45⁻/CD146⁺ stem-cell fraction, but also in lin⁻/CD271⁺/CD45⁻/CD146(⁻/low) cells. Both populations, regardless of CD146 expression, shared a similar phenotype and genotype, gave rise to typical cultured stromal cells, and formed bone and hematopoietic stroma in vivo. Interestingly, CD146 was up-regulated in normoxia and down-regulated in hypoxia. This was correlated with in situ localization differences, with CD146 coexpressing reticular cells located in perivascular regions, whereas bone-lining MSCs expressed CD271 alone. In both regions, CD34⁺ hematopoietic stem/progenitor cells were located in close proximity to MSCs. These novel findings show that the expression of CD146 differentiates between perivascular versus endosteal localization of non-hematopoietic BM-MSC populations, which may be useful for the study of the hematopoietic environment.

AB - Nonhematopoietic bone marrow mesenchymal stem cells (BM-MSCs) are of central importance for bone marrow stroma and the hematopoietic environment. However, the exact phenotype and anatomical distribution of specified MSC populations in the marrow are unknown. We characterized the phenotype of primary human BM-MSCs and found that all assayable colony-forming units-fibroblast (CFU-Fs) were highly and exclusively enriched not only in the lin⁻/CD271⁺/CD45⁻/CD146⁺ stem-cell fraction, but also in lin⁻/CD271⁺/CD45⁻/CD146(⁻/low) cells. Both populations, regardless of CD146 expression, shared a similar phenotype and genotype, gave rise to typical cultured stromal cells, and formed bone and hematopoietic stroma in vivo. Interestingly, CD146 was up-regulated in normoxia and down-regulated in hypoxia. This was correlated with in situ localization differences, with CD146 coexpressing reticular cells located in perivascular regions, whereas bone-lining MSCs expressed CD271 alone. In both regions, CD34⁺ hematopoietic stem/progenitor cells were located in close proximity to MSCs. These novel findings show that the expression of CD146 differentiates between perivascular versus endosteal localization of non-hematopoietic BM-MSC populations, which may be useful for the study of the hematopoietic environment.

KW - Animals

KW - Antigens, CD146

KW - Bone Marrow Cells

KW - Cell Differentiation

KW - Cell Separation

KW - Cells, Cultured

KW - Female

KW - Flow Cytometry

KW - Fluorescent Antibody Technique

KW - Humans

KW - Mesenchymal Stem Cells

KW - Mice

KW - Mice, Inbred NOD

KW - Phenotype

KW - Polymerase Chain Reaction

KW - Transplantation, Heterologous

U2 - 10.1182/blood-2010-08-304287

DO - 10.1182/blood-2010-08-304287

M3 - Journal article

C2 - 21415267

VL - 117

SP - 5067

EP - 5077

JO - Blood

JF - Blood

SN - 0006-4971

IS - 19

ER -