2007 Thomas W. Smith Memorial Lecture—Biologic Tissue Repair: Tearing Pages out of Nature’s Playbook
The therapeutic implications of angiogenic growth factors were identified by the pioneering work of Folkman and colleagues more than 2 decades ago. Their work documented the extent to which tumor development was dependent upon neovascularization and suggested that this relationship might involve angiogenic growth factors, which were specific for neoplasms. Beginning 2 decades ago, a series of polypeptide growth factors were purified, sequenced, and demonstrated to be responsible for natural as well as pathological angiogenesis.
Subsequent investigations have established the feasibility of using recombinant formulations of such angiogenic growth factors to expedite and/or augment collateral artery development in animal models of myocardial and hindlimb ischemia. This novel strategy for the treatment of vascular insufficiency has been termed “therapeutic angiogenesis.”
Preclinical animal studies from multiple laboratories established that protein or gene therapy may be utilized to successfully accomplish therapeutic angiogenesis. In the course of these investigations, the role of circulating progenitor cells in neovascularization of ischemic tissue was identified. The finding that bone marrow–derived cells, so-called endothelial progenitor cells, were present in adult mammals and capable of contributing to ischemic tissue repair triggered a still-evolving paradigm in which natural repair mechanisms are being exploited therapeutically. Observations on the therapeutic effects of recapitulation of embryonic signaling pathways in postnatal life and the identification of multiple adult-derived progenitor and stem cells have fueled interest in leveraging innate mechanisms for tissue repair toward the ultimate goal of tissue regeneration.