Low oxygen tension maintains multipotency, whereas normoxia increases differentiation of mouse bone marrow stromal cells

Ina Berniakovich, Marco Giorgio

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Optimization of mesenchymal stem cells (MSC) culture conditions is of great importance for their more successful application in regenerative medicine. O2 regulates various aspects of cellular biology and, in vivo, MSC are exposed to different O2 concentrations spanning from very low tension in the bone marrow niche, to higher amounts in wounds. In our present work, we isolated mouse bone marrow stromal cells (BMSC) and showed that they contained a population meeting requirements for MSC definition. In order to establish the effect of low O2 on cellular properties, we examined BSMC cultured under hypoxic (3% O2) conditions. Our results demonstrate that 3% O2 augmented proliferation of BMSC, as well as the formation of colonies in the colony-forming unit assay (CFU-A), the percentage of quiescent cells, and the expression of stemness markers Rex-1 and Oct-4, thereby suggesting an increase in the stemness of culture when exposed to hypoxia. In contrast, intrinsic differentiation processes were inhibited by 3% O2. Overall yield of differentiation was dependent on the adjustment of O2 tension to the specific stage of BMSC culture. Thus, we established a strategy for efficient BMSC in vitro differentiation using an initial phase of cell propagation at 3% O2, followed by differentiation stage at 21% O2. We also demonstrated that 3% O2 affected BMSC differentiation in p53 and reactive oxygen species (ROS) independent pathways. Our findings can significantly contribute to the obtaining of high-quality MSC for effective cell therapy.

Original languageEnglish
Pages (from-to)2119-2134
Number of pages16
JournalInternational Journal of Molecular Sciences
Volume14
Issue number1
DOIs
Publication statusPublished - 2013

Fingerprint

oxygen tension
bone marrow
Mesenchymal Stromal Cells
mice
Bone
stem cells
Oxygen
Stem cells
Cell culture
cells
Cytology
hypoxia
Cell Culture Techniques
biology
medicine
Colony-Forming Units Assay
markers
therapy
Assays
Reactive Oxygen Species

Keywords

  • Bone marrow stromal cells
  • Differentiation
  • Hypoxia
  • Mesenchymal stem cells
  • Oxygen

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Spectroscopy
  • Inorganic Chemistry
  • Catalysis
  • Molecular Biology
  • Computer Science Applications
  • Medicine(all)

Cite this

@article{90eb2f94df354d96b13186ce6b0581a0,
title = "Low oxygen tension maintains multipotency, whereas normoxia increases differentiation of mouse bone marrow stromal cells",
abstract = "Optimization of mesenchymal stem cells (MSC) culture conditions is of great importance for their more successful application in regenerative medicine. O2 regulates various aspects of cellular biology and, in vivo, MSC are exposed to different O2 concentrations spanning from very low tension in the bone marrow niche, to higher amounts in wounds. In our present work, we isolated mouse bone marrow stromal cells (BMSC) and showed that they contained a population meeting requirements for MSC definition. In order to establish the effect of low O2 on cellular properties, we examined BSMC cultured under hypoxic (3{\%} O2) conditions. Our results demonstrate that 3{\%} O2 augmented proliferation of BMSC, as well as the formation of colonies in the colony-forming unit assay (CFU-A), the percentage of quiescent cells, and the expression of stemness markers Rex-1 and Oct-4, thereby suggesting an increase in the stemness of culture when exposed to hypoxia. In contrast, intrinsic differentiation processes were inhibited by 3{\%} O2. Overall yield of differentiation was dependent on the adjustment of O2 tension to the specific stage of BMSC culture. Thus, we established a strategy for efficient BMSC in vitro differentiation using an initial phase of cell propagation at 3{\%} O2, followed by differentiation stage at 21{\%} O2. We also demonstrated that 3{\%} O2 affected BMSC differentiation in p53 and reactive oxygen species (ROS) independent pathways. Our findings can significantly contribute to the obtaining of high-quality MSC for effective cell therapy.",
keywords = "Bone marrow stromal cells, Differentiation, Hypoxia, Mesenchymal stem cells, Oxygen",
author = "Ina Berniakovich and Marco Giorgio",
year = "2013",
doi = "10.3390/ijms14012119",
language = "English",
volume = "14",
pages = "2119--2134",
journal = "International Journal of Molecular Sciences",
issn = "1661-6596",
publisher = "MDPI AG",
number = "1",

}

TY - JOUR

T1 - Low oxygen tension maintains multipotency, whereas normoxia increases differentiation of mouse bone marrow stromal cells

AU - Berniakovich, Ina

AU - Giorgio, Marco

PY - 2013

Y1 - 2013

N2 - Optimization of mesenchymal stem cells (MSC) culture conditions is of great importance for their more successful application in regenerative medicine. O2 regulates various aspects of cellular biology and, in vivo, MSC are exposed to different O2 concentrations spanning from very low tension in the bone marrow niche, to higher amounts in wounds. In our present work, we isolated mouse bone marrow stromal cells (BMSC) and showed that they contained a population meeting requirements for MSC definition. In order to establish the effect of low O2 on cellular properties, we examined BSMC cultured under hypoxic (3% O2) conditions. Our results demonstrate that 3% O2 augmented proliferation of BMSC, as well as the formation of colonies in the colony-forming unit assay (CFU-A), the percentage of quiescent cells, and the expression of stemness markers Rex-1 and Oct-4, thereby suggesting an increase in the stemness of culture when exposed to hypoxia. In contrast, intrinsic differentiation processes were inhibited by 3% O2. Overall yield of differentiation was dependent on the adjustment of O2 tension to the specific stage of BMSC culture. Thus, we established a strategy for efficient BMSC in vitro differentiation using an initial phase of cell propagation at 3% O2, followed by differentiation stage at 21% O2. We also demonstrated that 3% O2 affected BMSC differentiation in p53 and reactive oxygen species (ROS) independent pathways. Our findings can significantly contribute to the obtaining of high-quality MSC for effective cell therapy.

AB - Optimization of mesenchymal stem cells (MSC) culture conditions is of great importance for their more successful application in regenerative medicine. O2 regulates various aspects of cellular biology and, in vivo, MSC are exposed to different O2 concentrations spanning from very low tension in the bone marrow niche, to higher amounts in wounds. In our present work, we isolated mouse bone marrow stromal cells (BMSC) and showed that they contained a population meeting requirements for MSC definition. In order to establish the effect of low O2 on cellular properties, we examined BSMC cultured under hypoxic (3% O2) conditions. Our results demonstrate that 3% O2 augmented proliferation of BMSC, as well as the formation of colonies in the colony-forming unit assay (CFU-A), the percentage of quiescent cells, and the expression of stemness markers Rex-1 and Oct-4, thereby suggesting an increase in the stemness of culture when exposed to hypoxia. In contrast, intrinsic differentiation processes were inhibited by 3% O2. Overall yield of differentiation was dependent on the adjustment of O2 tension to the specific stage of BMSC culture. Thus, we established a strategy for efficient BMSC in vitro differentiation using an initial phase of cell propagation at 3% O2, followed by differentiation stage at 21% O2. We also demonstrated that 3% O2 affected BMSC differentiation in p53 and reactive oxygen species (ROS) independent pathways. Our findings can significantly contribute to the obtaining of high-quality MSC for effective cell therapy.

KW - Bone marrow stromal cells

KW - Differentiation

KW - Hypoxia

KW - Mesenchymal stem cells

KW - Oxygen

UR - http://www.scopus.com/inward/record.url?scp=84877056819&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84877056819&partnerID=8YFLogxK

U2 - 10.3390/ijms14012119

DO - 10.3390/ijms14012119

M3 - Article

C2 - 23340651

AN - SCOPUS:84877056819

VL - 14

SP - 2119

EP - 2134

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 1

ER -