Potentiating Mesenchymal Stem Cells for Cardiac Regeneration

Cincinnati, Ohio -

Mesenchymal stem cells are attractive for therapeutics development because they can theoretically be used as a "one size fits all".  Additionally, their ability to home to area of tissue injury, in part by CXCR4 expression allows for intravenous administration, thus increasing their attractiveness for therapeutic use.  Currently there are numerous clinical trials ongoing with mesenchymal stem cells administered intravenously.

Initial work with mesenchymal stem cells in cardiac patients has demonstrated statistically significant benefit in patients administered intravenous allogeneic mesenchymal stem cells after infarction. 

Many researchers are trying to figure out ways how to potentiate therapeutic effects of mesenchymal stem cells.  In a recent publication (Haider et al. IGF-1-Overexpressing Mesenchymal Stem Cells Accelerate Bone Marrow Stem Cell Mobilization via Paracrine Activation of SDF-1 alpha}/CXCR4 Signaling to Promote Myocardial Repair. Circ Res. 2008 Oct 23), Mesenchymal stem cells were transfected with the gene for Insulin Like Growth Factor (IGF)-1.  This gene is important for many of the therapeutic activities of stem cells.  For example, it was demonstrated that the ability of mesenchymal stem cells to reverse kidney failure was primarily due to secretion of IGF-1. 

In the current study investigators demonstrated that transfection with IGF-1 allowed the mesenchymal stem cells to possess superior ability to inhibit post-infarct pathological changes in a model of heart attack.  Additionally, it was demonstrated that the degree of cardiac repair was associated with mobilization of endogenous bone marrow stem cells.  This is somewhat reminiscent of the experiences in critical limb ischemia, where the extent of responsiveness to bone marrow stem cell injection was correlated with extent of endogenous stem cell mobilization. 

It will be interesting to see whether such approaches to "supercharge" stem cells will be attempted with other kinds of mesenchymal stem cells as well.

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