Conclusions

Vascular maturation and induction are complementary targets in the design of novel strategies for therapeutic angiogenesis, which hold significant promise to overcome some of the difficulties that have emerged with the use of single factors, like VEGF. Tremendous advancements have taken place over the past few years in our understanding of the basic mechanisms regulating the different steps of vessel growth and maturation in physiology and development. The rational design of new therapeutic angiogenesis strategies should certainly take advantage of this biological knowledge.

The initial results in preclinical models have been sometimes contradictory and this is most likely due to the use of many different delivery systems, animal models and morphological or functional readouts. The potential of vascular maturation strategies to increase both the safety and the efficacy of therapeutic angiogenesis is exciting, although the real efficacy of these concepts remains to be determined by rigorous investigation of clinically relevant parameters, as proposed by Yla-Herttuala [72]. In particular, it will be fundamental to understand, for individual combinations and delivery systems, the dose-dependency of the therapeutic effects, the minimum required duration of treatment in order to achieve durable vascular growth, as well as the dose-limiting toxicities, which may be different from the ones emerged with the use of single angiogenic factors.

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