Low physiologic oxygen tensions reduce proliferation and differentiation of human multipotent mesenchymal stromal cells

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Low physiologic oxygen tensions reduce proliferation and differentiation of human multipotent mesenchymal stromal cells. / Holzwarth, Christina; Vaegler, Martin; Gieseke, Friederike; Pfister, Stefan M; Handgretinger, Rupert; Kerst, Gunter; Müller, Ingo.

In: BMC CELL BIOL, Vol. 11, 2010, p. 11.

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@article{cae446e447594a83b08febd828841b54,
title = "Low physiologic oxygen tensions reduce proliferation and differentiation of human multipotent mesenchymal stromal cells",
abstract = "BACKGROUND: Human multipotent mesenchymal stromal cells (MSC) can be isolated from various tissues including bone marrow. Here, MSC participate as bone lining cells in the formation of the hematopoietic stem cell niche. In this compartment, the oxygen tension is low and oxygen partial pressure is estimated to range from 1% to 7%. We analyzed the effect of low oxygen tensions on human MSC cultured with platelet-lysate supplemented media and assessed proliferation, morphology, chromosomal stability, immunophenotype and plasticity.RESULTS: After transferring MSC from atmospheric oxygen levels of 21% to 1%, HIF-1alpha expression was induced, indicating efficient oxygen reduction. Simultaneously, MSC exhibited a significantly different morphology with shorter extensions and broader cell bodies. MSC did not proliferate as rapidly as under 21% oxygen and accumulated in G1 phase. The immunophenotype, however, was unaffected. Hypoxic stress as well as free oxygen radicals may affect chromosomal stability. However, no chromosomal abnormalities in human MSC under either culture condition were detected using high-resolution matrix-based comparative genomic hybridization. Reduced oxygen tension severely impaired adipogenic and osteogenic differentiation of human MSC. Elevation of oxygen from 1% to 3% restored osteogenic differentiation.CONCLUSION: Physiologic oxygen tension during in vitro culture of human MSC slows down cell cycle progression and differentiation. Under physiological conditions this may keep a proportion of MSC in a resting state. Further studies are needed to analyze these aspects of MSC in tissue regeneration.",
keywords = "Adolescent, Bone Marrow Cells, Cell Differentiation, Cell Hypoxia, Cell Proliferation, Child, Child, Preschool, Chromosomal Instability, Female, G1 Phase, Humans, Hypoxia-Inducible Factor 1, alpha Subunit, Immunophenotyping, Infant, Male, Mesenchymal Stromal Cells, Multipotent Stem Cells, Stromal Cells",
author = "Christina Holzwarth and Martin Vaegler and Friederike Gieseke and Pfister, {Stefan M} and Rupert Handgretinger and Gunter Kerst and Ingo M{\"u}ller",
year = "2010",
doi = "10.1186/1471-2121-11-11",
language = "English",
volume = "11",
pages = "11",
journal = "BMC CELL BIOL",
issn = "1471-2121",
publisher = "BioMed Central Ltd.",

}

RIS

TY - JOUR

T1 - Low physiologic oxygen tensions reduce proliferation and differentiation of human multipotent mesenchymal stromal cells

AU - Holzwarth, Christina

AU - Vaegler, Martin

AU - Gieseke, Friederike

AU - Pfister, Stefan M

AU - Handgretinger, Rupert

AU - Kerst, Gunter

AU - Müller, Ingo

PY - 2010

Y1 - 2010

N2 - BACKGROUND: Human multipotent mesenchymal stromal cells (MSC) can be isolated from various tissues including bone marrow. Here, MSC participate as bone lining cells in the formation of the hematopoietic stem cell niche. In this compartment, the oxygen tension is low and oxygen partial pressure is estimated to range from 1% to 7%. We analyzed the effect of low oxygen tensions on human MSC cultured with platelet-lysate supplemented media and assessed proliferation, morphology, chromosomal stability, immunophenotype and plasticity.RESULTS: After transferring MSC from atmospheric oxygen levels of 21% to 1%, HIF-1alpha expression was induced, indicating efficient oxygen reduction. Simultaneously, MSC exhibited a significantly different morphology with shorter extensions and broader cell bodies. MSC did not proliferate as rapidly as under 21% oxygen and accumulated in G1 phase. The immunophenotype, however, was unaffected. Hypoxic stress as well as free oxygen radicals may affect chromosomal stability. However, no chromosomal abnormalities in human MSC under either culture condition were detected using high-resolution matrix-based comparative genomic hybridization. Reduced oxygen tension severely impaired adipogenic and osteogenic differentiation of human MSC. Elevation of oxygen from 1% to 3% restored osteogenic differentiation.CONCLUSION: Physiologic oxygen tension during in vitro culture of human MSC slows down cell cycle progression and differentiation. Under physiological conditions this may keep a proportion of MSC in a resting state. Further studies are needed to analyze these aspects of MSC in tissue regeneration.

AB - BACKGROUND: Human multipotent mesenchymal stromal cells (MSC) can be isolated from various tissues including bone marrow. Here, MSC participate as bone lining cells in the formation of the hematopoietic stem cell niche. In this compartment, the oxygen tension is low and oxygen partial pressure is estimated to range from 1% to 7%. We analyzed the effect of low oxygen tensions on human MSC cultured with platelet-lysate supplemented media and assessed proliferation, morphology, chromosomal stability, immunophenotype and plasticity.RESULTS: After transferring MSC from atmospheric oxygen levels of 21% to 1%, HIF-1alpha expression was induced, indicating efficient oxygen reduction. Simultaneously, MSC exhibited a significantly different morphology with shorter extensions and broader cell bodies. MSC did not proliferate as rapidly as under 21% oxygen and accumulated in G1 phase. The immunophenotype, however, was unaffected. Hypoxic stress as well as free oxygen radicals may affect chromosomal stability. However, no chromosomal abnormalities in human MSC under either culture condition were detected using high-resolution matrix-based comparative genomic hybridization. Reduced oxygen tension severely impaired adipogenic and osteogenic differentiation of human MSC. Elevation of oxygen from 1% to 3% restored osteogenic differentiation.CONCLUSION: Physiologic oxygen tension during in vitro culture of human MSC slows down cell cycle progression and differentiation. Under physiological conditions this may keep a proportion of MSC in a resting state. Further studies are needed to analyze these aspects of MSC in tissue regeneration.

KW - Adolescent

KW - Bone Marrow Cells

KW - Cell Differentiation

KW - Cell Hypoxia

KW - Cell Proliferation

KW - Child

KW - Child, Preschool

KW - Chromosomal Instability

KW - Female

KW - G1 Phase

KW - Humans

KW - Hypoxia-Inducible Factor 1, alpha Subunit

KW - Immunophenotyping

KW - Infant

KW - Male

KW - Mesenchymal Stromal Cells

KW - Multipotent Stem Cells

KW - Stromal Cells

U2 - 10.1186/1471-2121-11-11

DO - 10.1186/1471-2121-11-11

M3 - SCORING: Journal article

C2 - 20109207

VL - 11

SP - 11

JO - BMC CELL BIOL

JF - BMC CELL BIOL

SN - 1471-2121

ER -