Angiogenesis represents an emerging field that is relevant to an expanding group of conditions. Although the development of angiogenesis inhibitors for the treatment of cancer represented the focus of early attention, this therapeutic class has now expanded to include conditions such as rheumatoid arthritis. On the other hand, molecules able to stimulate angiogenesis are gaining interest as candidate treatments of various ischemic diseases. Thrombolytic, antithrombotic and anticoagulant treatments represent the major acute therapeutic options for the treatment of myocardial infarction and peripheral arterial occlusive disease. However, in the days and weeks following myocardial damage, strategies to prevent further ischemic cell death or to promote the recovery of damaged tissue may be of greater advantage, particularly for patients with congestive heart failure. Stimulators of angiogenesis may help meet this clinical demand and in doing so this therapeutic class is expected to boost the market for modulators of angiogenesis. The majority of angiogenesis-related molecules in advanced development are target VEGF however stem cell treatment is rapidly emerging as an alternative.

Preclinical studies have established that implantation of bone marrow-mononuclear cells into ischemic limbs increases collateral vessel formation and these finding have now been replicated in humans with peripheral arterial disease. The therapeutic potential of stem cell treatment of myocardial infarction has also been investigated. Direct myocardial injection of bone marrow cells in a rat ischemic heart model induced angiogenesis. This study was then repeated in a pilot trial of humans. In this study the injection of autologous AC133+ bone-marrow cells into the infarct border zone in six patients who had had a myocardial infarction and undergone coronary artery bypass grafting was performed. This treatment was safe and produced an improvement in left-ventricular function and infarct tissue perfusion. A further study performed in Germany compared patient responses in two groups. Compared to acute myocardial infarction patient treated by standard therapy alone, a group that received additional stem cell treatment reduced infarct volume as well as increases in infarction wall movement velocity, stroke volume index, left ventricular end-systolic volume and contractility, and myocardial perfusion of the infarct region. Most recently an independent study conducted by researchers in Hong Kong also found that the injection of autologous mononuclear bone marrow cells into the ischemic myocardium of eight patients with severe ischemic heart disease via novel catheter-based technology produced an improvement in symptoms, myocardial perfusion, and function at the ischemic region. This data is all the more impressive considering that none of the patients were responding to traditional medical and surgical therapy. This new procedure avoids the risks and complications of open-heart surgery, and can be performed under local anaesthesia as a day procedure. Hence the body of data supporting the use of stem cell treatment of ischemic diseases is rapidly growing. In response to this development a number of companies are now involved in commercializing this approach.

Entry date January, 2003

Adapted from Tse et al, Lancet 2003 Jan 4;361(9351):47-9 - Interested in collaborating with this group? Contact LeadDiscovery or the authors direct.