Bone marrow cell-mediated cardiovascular repair: potential of combined therapies.
Recent evidence indicates that bone-marrow cells (BMCs) can contribute to the healing process of the injured cardiovascular system via the chemokine receptor CXCR4/SDF-1, thymosin beta(4) and integrin alpha(4)beta(1) molecular pathways. During tissue ischemia overwhelming numbers of detrimental oxygen radicals are generated, and therefore treatment with antioxidants and L-arginine, the precursor of nitric oxide (NO), could induce beneficial effects beyond those achieved by BMC transplantation alone. Recent studies have reported that BMCs have enhanced neovascularization capacity in cotreatment with alpha-tocopherol (vitamin E), ascorbic acid (vitamin C) and L-arginine. Moreover, BMC therapy can be combined with gene therapy. Clinical trials employing BMCs in the treatment of cardiovascular diseases have been completed with mixed or positive results, and several trials are ongoing. Here, we discuss the clinical potential of BMC transplantation alone and in combined therapy that aims to restore organ vascularization and function. We also consider the mechanisms of mobilization, differentiation and incorporation of BMCs.