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Physiology in Press

First published online on March 18, 2005.
Experimental Physiology (2005)
DOI: 10.1113/expphysiol.2004.028571
© The Physiological Society 2005

A more recent version of this article appeared on May 1, 2005
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Received January 18, 2005
Revised February 18, 2005
Accepted after revision March 2, 2005


Cardiovascular control

Therapeutic angiogenesis and vasculogenesis for tissue regeneration

Paolo Madeddu 1*

1 Bristol University

* To whom correspondence should be addressed. E-mail: madeddu{at}yahoo.com.


   Abstract
Abstract. Therapeutic angiogenesis/vasculogenesis holds promise for the cure of ischemic disease. The approach postulates the manipulation of spontaneous healing response by supplementation of growth factors or transplantation of vascular progenitor cells. These supplements are intended to foster the formation of arterial collaterals and promote the regeneration of damaged tissues. Angiogenic factors are generally delivered in form of recombinant proteins or by gene transfer using viral vectors. In addition, new non-viral methods are gaining importance for their safer profile. The association of growth factors with different biological activity might offer distinctive advantages in terms of efficacy, yet combinatory approaches require further optimization. Alternatively, substances endowed of pleiotropic activity might be considered, in virtue of their ability to target multiple mechanisms. For instance, some angiogenic factors not only stimulate the growth of arterioles and capillaries, but also inhibit vascular destabilization triggered by metabolic and oxidative stress. Transplantation of endothelial progenitor cells was recently proposed for the treatment of peripheral and myocardial ischemia. Progenitor cells can be transplanted either without any preliminary conditioning or after ex vivo genetic manipulation. Delivery of genetically modified progenitor cells eliminates the drawback of immune response against viral vectors and makes feasible repeating the therapeutic procedure in case of injury recurrence. It is envisioned that these new approaches of regenerative medicine will open unprecedented opportunities for the care of life-threatening diseases.

Key Words: Angiogenesis, Endothelial cell







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