Allogeneic MSC for Restenosis

Naples, Italy -

The inherent antiinflammatory activities of mesenchymal stem cells have been leveraged for treatment of diseases associated with uncontrolled production of inflammatory mediators such as graft versus host disease and Crohn's Disease.  Indications for which mesenchymal stem cells are currently in Phase III of clinical trials by the company Osiris Therapeutics.

In a recent paper (Forte et al. Mesenchymal stem cells effectively reduce surgically induced stenosis in rat carotids. J Cell Physiol, 2008 Aug 8.) allogeneic bone marrow derived mesenchymal stem cells are used to treat the condition of restenosis.  This pathological inflammation derived process causes narrowing of blood vessels, and is usually a problem after stenting or balloon angioplasty.  Since the process is associated with endothelial injury, the authors wondered whether administration of mesenchymal stem cells could repair the injured blood vessel and thus inhibit the incidence of re-narrowing.

Rat carotid arteriotomy was performed and administration of 5 million allogeneic bone marrow derived mesenchymal stem cells was performed intravenously. 

Allogeneic stem cells homed to the injured carotid artery but not to control uninjured vessels.  A statistically significant preservation of lumen size was maintained in animals treated with mesenchymal stem cells as comparted to controls.  This difference was observed up until cessation of the experiment, which was on day 30. 

The allogeneic mesenchymal stem cells induced a decrease in the inflammatory cytokines interleukin-1 and monocyte chemoattractant protein-1, as well as upregulated production of TGF-beta.

These data are in line with other studies in which it has been demonstrated that mobilization of endogenous stem cells by treatment with agents such as G-CSF leads to inhibition of restenosis and suppressed neointimal formation (Wu et al. Effects of granulocyte-colony stimulating factor on the repair of balloon-injured arteries. Pathology 2008 Aug;40(5):513-9).