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

BMC Cell Biology

Research Article

Stefan M Pfister¹  Christina Holzwarth²  Friederike Gieseke²  Ingo Müller²  Martin Vaegler²  Rupert Handgretinger²  Gunter Kerst³ 

[1] German Cancer Research Center and University Children's Hospital, Heidelberg, Germany;University Children's Hospital, Department of General Pediatrics, Hematology and Oncology, Tübingen, Germany;University Children's Hospital, Department of Pediatric Cardiology, Pulmology and Intensive Care, Tübingen, Germany;

关键词: Oxygen Tension;    Osteogenic Differentiation;    Mesenchymal Stromal Cell;    Stem Cell Niche;    Platelet Lysate;   

DOI  :  10.1186/1471-2121-11-11

 received in 2009-07-07, accepted in 2010-01-28,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundHuman 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.ResultsAfter transferring MSC from atmospheric oxygen levels of 21% to 1%, HIF-1α 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.ConclusionPhysiologic 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.

【 授权许可】

Unknown   
© Holzwarth et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.