Mesenchymal stem cells genetically modified with the angiopoietin-1 gene enhanced arteriogenesis in a porcine model of chronic myocardial ischaemia.

ABSTRACT

The direct injection by thoracoscope of mesenchymal stem cells (MSCs) that had been genetically modified to express angiopoietin-1 was investigated in a porcine model to determine their effect on arteriogenesis and the effectiveness of this technique. Chronic myocardial ischaemia was established using a thoracoscope to insert an ameroid constrictor around the left circumflex coronary artery. Six weeks after establishing the ischaemia, 20 pigs were randomly divided into three groups to receive injections by thoracoscope of either genetically-modified MSCs, unmodified MSCs or phosphate-buffered saline into the ischaemic border area. The injections were repeated 1 month later. The genetically modified MSCs were found to restore blood flow significantly more than the other observed treatments and immunohistochemical evaluation of arteriogenesis supported this finding. In conclusion, the injection of MSCs that had been genetically modified to express angiopoietin-1 improved arteriogenesis and increased collateral blood flow in the myocardial ischaemic area. Thoracoscope delivery of the injection was safe and minimally invasive.