Table 1.
Overview of preclinical and clinical studies of HGF gene therapy in MI and ischaemic disease
| Methods used in the study | Results | Model | Reference | Year | |
|---|---|---|---|---|---|
| Preclinical studies | HGF gene transfer in ischaemia | Improved angiogenesis | Rat | [40] | 2000 |
| HGF gene transfer in hind-limb ischaemia | Significantly increased blood flow | Rat | [42] | 2001 | |
| Administration of an adenoviral vector expressing HGF after ligation of coronary arteries | Preserved myocardial function and geometry; decreased left ventricular dilatation and preserved wall thickness; reduced apoptosis of interstitial cells in the infarcted tissue | Mouse | [25] | 2003 | |
| Intramyocardial injection of human HGF plasmid DNA in ischaemic cardiomyopathy | Improved cardiac function through increase in blood flow and decrease in fibrosis | Pig | [68] | 2006 | |
| Adenovirus-mediated high expression of human HGF | Increased functional arterioles and improved collateral artery growth | Pig | [163] | 2006 | |
| Bone marrow-derived mesenchymal stem cells combined with HGF transplantation in acute MI | Improved left ventricular ejection fraction, left ventricular end systolic volume and end diastolic volume; greater cardiac perfusion, growth of collateral arteries and number of vessels | Pig | [165] | 2006 | |
| Adenovirus-mediated HGF gene transfer in chronic myocardial ischaemia | Enhanced myocardial perfusion; higher density of newly formed blood vessels and number of collateral blood vessels; reduced area of myocardial ischaemia and improved left ventricular ejection fraction | Minipig | [164] | 2008 | |
| Clinical trials | Phase I clinical trials; intramuscular injection of naked HGF plasmid DNA in patients with critical limb ischaemia | No severe complications or adverse effects in any patient | Human | [168] | 2004 |
| Open-label, safety and tolerance trial of Ad-HGF in 18 patients suffering from coronary heart disease; direct intramyocardial administration of the Ad-HGF | No evidence of systemic or heart-related adverse effects; Ad-HGF was well tolerated and improved myocardial perfusion with a dose–effect relationship | Human | [166] | 2008 | |
| Phase I clinical trial; use of an adenovirus gene-transfer vector to deliver the human HGF gene to individuals with clinically significant coronary artery disease by direct intracoronary injection | HGF gene transfer is safe and feasible | Human | [167] | 2009 |