Effects of hypoxia on human mesenchymal stem cell expansion and plasticity in 3D constructs

Warren L Grayson, Feng Zhao, Reza Izadpanah, Bruce Bunnell, Teng Ma

Research output: Contribution to journalArticle

Abstract

Low oxygen tension is thought to be an integral component of the human mesenchymal stem cell (hMSC) native bone marrow microenvironment. HMSC were cultured under physiologically relevant oxygen environments (2% O2) in three-dimensional (3D) constructs for up to 1 month in order to investigate the combined effects of chronic hypoxia and 3D architecture on hMSC tissue-development patterns. Hypoxic hMSC exhibited an extended lag phase in order to acclimatize to culture conditions. However, they subsequently proliferated continuously throughout the culture period, while maintaining significantly higher colony-forming unit capabilities and expressing higher levels of stem cell genes than hMSC cultured at 20% O2 (normoxic) conditions. Upon induction, hypoxic hMSC also expressed higher levels of osteoblastic and adipocytic differentiation markers than normoxic controls. Hypoxia induced increased total protein levels in hMSC throughout the culture period, as well as significantly different fibronectin expression patterns suggesting that oxygen levels can significantly affect tissue-development patterns. Importantly, hMSC maintained the ability to thrive in prolonged hypoxic conditions suggesting that hypoxia may be an essential element of the in vivo hMSC niche. Further studies are required to determine how variations in cellular characteristics and ECM expression impact on the physiological properties of the engineered tissue, yet these results strongly indicate that oxygen tension is a key parameter that influences the in vitro characteristics of hMSC and their development into tissues.

Original languageEnglish (US)
Pages (from-to)331-339
Number of pages9
JournalJournal of Cellular Physiology
Volume207
Issue number2
DOIs
StatePublished - May 2006
Externally publishedYes

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Stem cells
Mesenchymal Stromal Cells
Plasticity
Oxygen
Tissue
Stem Cells
Stem Cell Niche
Cell Plasticity
Hypoxia
Military electronic countermeasures
Differentiation Antigens
Fibronectins
Cell culture
Cell Culture Techniques
Bone Marrow
Bone
Genes

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

Effects of hypoxia on human mesenchymal stem cell expansion and plasticity in 3D constructs. / Grayson, Warren L; Zhao, Feng; Izadpanah, Reza; Bunnell, Bruce; Ma, Teng.

In: Journal of Cellular Physiology, Vol. 207, No. 2, 05.2006, p. 331-339.

Research output: Contribution to journalArticle

Grayson, Warren L ; Zhao, Feng ; Izadpanah, Reza ; Bunnell, Bruce ; Ma, Teng. / Effects of hypoxia on human mesenchymal stem cell expansion and plasticity in 3D constructs. In: Journal of Cellular Physiology. 2006 ; Vol. 207, No. 2. pp. 331-339.
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