Differential Expression of Insulin-Like Growth Factor-I Receptor on Human Bone Marrow-Derived Mesenchymal Stem Cells Induced by Tumor Necrosis Factor-?

Abstract

Background: Cell-based therapy has been implicated in the treatment of liver diseases. Mesenchymal stem cells from various sources such as bone marrow are available. These cells are one of the major candidates in cell therapy. The production of insulin-like growth factor-I increases in the regenerating organ. The insulin-like growth factor-I in liver regeneration is effective after binding to insulin-like growth factor-I receptor.

Objective: To test our hypothesis that tumor necrosis factor-α can stimulate mesenchymal stem cells to express insulin-like growth factor-I receptor.

Methods: Bone marrow was aspirated from normal human donor after taking informed consent. Cells were isolated and cultured. Identification of cells was done by flowcytometry and functional tests. The fourth passage cells were treated with tumor necrosis factor-α at two doses of 1 and 10 ng/mL, and incubated for 2, 10, 24, and 48 hours. Insulin-like growth factor-I receptor gene expression was studied using real-time polymerase chain reaction.

Results: Flowcytometry showed that the human bone marrow mesenchymal stem cells were positive for CD90 and negative for CD45 and CD80. The insulin-like growth factor-I receptor gene expression was increased in tumor necrosis factor-α treated in comparison with untreated cells.

Conclusion: Treatment of human bone marrow-derived mesenchymal stem cells with tumor necrosis factor-α increases gene expression of insulin-like growth factor-I receptor. This finding may be used for increasing the effectiveness of stem cell therapy in those with acute hepatic failure.