Lactate

Lactate is lactic acid.

Lactate Influences the Gene Expression Profile of Human Mesenchymal Stem Cells (hMSC) in a Dose Dependant Manner.

"Lactate [stimulates] collagen synthesis and vessel growth. Lactate, in vivo, plays an important role in homing of stem cells. hMSCs were obtained from bone marrow. Subsequently the hMSCs were treated with either 0, 5, 10 and 15 mM lactate (pH 7,4) for 24 hours. RNA Isolation from stimulated hMSCs and controls was performed. Lactate in moderate concentrations of 5 respectively 10 mM leads to an anti-inflammatory, anti-apoptotic but growth and proliferation promoting gene expression after 24 h. In contrast, high lactate concentrations of 15 mM leads to the opposed effect, namely promoting inflammation and apoptosis. Hypoxia induced genes did not show any significant regulation. Contrary to expectation, we were not able to show any significant regulation of candidates associated with glycolysis."

TGF-Beta was only upregulated 1.794 fold 10 mM and not 5 and 15 fold.  VEGF-A was upregulated at 10 and 15 mM but VEGF-B was only upregulated at 15 mM.  Expression of the pro-chondrogenic HIF-1a peaked at 10 mM but was not statistically significant.


Lactate modulates gene expression in human mesenchymal stem cells.

"Surgical wounds are characterised by elevated tissue lactate concentrations. This accumulated lactate is capable of stimulating collagen synthesis and new vessel growth as well. Lactate is  able to favour homing of stem cells.

MSC were isolated from human bone marrow using the density gradient technique and incubated with alpha-methoxyethoxymethyl containing 10% fetal calf serum at 37 degrees C under 95% air and 5% CO(2). MSC were treated with 15 mM lactate for different time periods (1, 6 and 24 h and 3 and 7 days). A significant alteration of gene expression was defined as a two-fold stimulation or inhibition. 

Gene expression analysis shows 63 up- and 51 down-regulated genes after 1 h of treatment, 45 up- and 47 down-regulated genes after 6 h of treatment, 57 up- and 72 down-regulated genes after 24 h of treatment, 103 up- and 28 down-regulated genes after 3 days of treatment and 50 up- and 101 down-regulated genes after 7 days of treatment with lactate. The majority of the modulated genes are related to the expression of cytokines, transcription factors and cell-cycle- or cellular-matrix-associated proteins. In particular, lactate up-regulates the expression of interleukin-6{up} (3 days, 4.11-fold), of heat shock protein 70 (3 days, 2.36-fold) and of hypoxia-inducible factor-1alpha (3 days, 2.09-fold). A down-regulating effect of lactate is observed for superoxide dismutase 2 (1 h, 0.5-fold; 24 h, 0.4-fold; 7 days, 0.32-fold) and BCL2-associated X protein (24 h, 0.42-fold; 7 days, 0.4-fold). Expression of cell surface antigens clusters of differentiation 29, 44, 59, 73, 90, 105, 106 and 146 does not change over the time period of lactate treatment."