PGC-1α: The Missing Ingredient for Mesenchymal Stem Cell–Mediated Angiogenesis

Diabetes is a vascular disease. As blood vessels become damaged, loss of flow leads to ischemia of critical organs. This results in coronary artery disease (CAD), stroke, and peripheral artery disease (PAD) due to large vessel damage, as well as retinopathy and nephropathy due to small vessel injury. These vascular complications are the greatest contributors to diabetes-associated morbidity and mortality as well as healthcare costs related to diabetes, which are approaching $200 billion. The incidence of cardiac and vascular disease is expected to rise steadily as a result of the current epidemic of diabetes (1). Thus, there is an urgent need for novel therapies targeting large vessel damage.

Therapeutic angiogenesis offers great potential as a strategy to treat large vessel disease. Although the angiogenic factor vascular endothelial growth factor (VEGF) has been tested extensively, results from over two dozen clinical trials in cardiac and limb ischemia have been largely unsuccessful (2). However, improved delivery modalities may enhance VEGF efficacy, although additional angiogenic and growth factors may be required for functional vessel development, since VEGF alone generally induces formation of incomplete, leaky vessels. Approaches to use of mesencymal stem cells (MSCs) that have the capacity to promote angiogenesis are in their infancy, but small clinical studies suggest promise in CAD …