The metabolism of human mesenchymal stem cells during proliferation and differentiation

@article{Pattappa2011TheMO,
  title={The metabolism of human mesenchymal stem cells during proliferation and differentiation},
  author={Girish Pattappa and Hannah K. Heywood and Joost D de Bruijn and David A Lee},
  journal={Journal of Cellular Physiology},
  year={2011},
  volume={226}
}
Human mesenchymal stem cells (MSCs) reside under hypoxic conditions in vivo, between 4% and 7% oxygen. Differentiation of MSCs under hypoxic conditions results in inhibited osteogenesis, while chondrogenesis is unaffected. The reasons for these results may be associated with the inherent metabolism of the cells. The present investigation measured the oxygen consumption, glucose consumption and lactate production of MSCs during proliferation and subsequent differentiation towards the osteogenic… 
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References

SHOWING 1-10 OF 73 REFERENCES
Metabolic Flexibility Permits Mesenchymal Stem Cell Survival in an Ischemic Environment
TLDR
It is demonstrated that MSCs have a profoundly greater capacity to survive under conditions of ischemia compared with cardiomyocytes, measured by detecting changes in cellular morphology, caspase activity and phosphatidylserine exposure, and that glycolysis has specific prosurvival functions, independent of energy production in M SCs.
Ex vivo expansion of human mesenchymal stem cells: A more effective cell proliferation kinetics and metabolism under hypoxia
TLDR
A more efficient BM MSC expansion at 2% O2, compared to normoxic conditions, is demonstrated, associated to an earlier start of cellular division and supported by an increase in cellular metabolism efficiency towards the maximization of cell yield for application in clinical settings.
Coordinated Changes of Mitochondrial Biogenesis and Antioxidant Enzymes During Osteogenic Differentiation of Human Mesenchymal Stem Cells
TLDR
This study investigated the changes of mitochondrial biogenesis and bioenergetic function using human mesenchymal stem cells (hMSCs) because of their well‐defined differentiation potentials and suggested an energy production transition from glycolysis to oxidative phosphorylation in hMSCs upon osteogenic induction.
Low oxygen reduces the modulation to an oxidative phenotype in monolayer‐expanded chondrocytes
TLDR
It is concluded that simply transferring chondrocytes to low oxygen is not sufficient to either maintain or re‐establish a normal energy metabolism, and the hypothesis that the shift towards an oxidative energy metabolism is driven by morphological changes is not supported.
Metabolic and Functional Characterization of Human Adipose-Derived Stem Cells in Tissue Engineering  
TLDR
The data show that adipose-derived stem cells remain viable under adverse conditions of low glucose, glutamine, and oxygen concentrations, however, there are variable levels of differentiation in the various culture conditions, which could lead to challenges in de novo osteogenesis and other forms of tissue engineering.
Influence of oxygen on the proliferation and metabolism of adipose derived adult stem cells
TLDR
Oxygen tension may play an important role in regulating the proliferation and metabolism of hADAS cells as they undergo chondrogenesis, and the exogenous control of oxygen tension may provide a means of increasing the overall accumulation of matrix macromolecules in tissue‐engineered cartilage.
Effects of hypoxia on human mesenchymal stem cell expansion and plasticity in 3D constructs
TLDR
Results strongly indicate that oxygen tension is a key parameter that influences the in vitro characteristics of hMSC and their development into tissues.
Effects of glutamine, glucose, and oxygen concentration on the metabolism and proliferation of rabbit adipose-derived stem cells.
TLDR
ASCs are a viable source of stem cells for tissue engineering purposes, although substantial challenges remain and may be able to survive brief periods of limited nutrient transport after implantation in environments with limited oxygen and glutamine.
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