Biomedical Engineering Reference
In-Depth Information
therapies hold promise for rebuilding tissues to treat wounds, ulcers, coronary
artery disease, stroke, emphysema, and ischemic conditions in general. Anti-
angiogenic therapies hold promise for treating cancer and inflammation. However,
pro-angiogenic and anti-angiogenic approaches have not yet realized their
potential in the clinic. As exemplified by therapeutic angiogenesis for coronary
artery disease, the promotion of angiogenesis in human tissues is challenging, and
successes in pre-clinical studies have not translated to large-scale clinical trials. As
exemplified by angiogenesis inhibitors for cancer therapy, tissues often develop
resistance to angiogenesis-blocking agents, and anti-angiogenic agents often lose
their efficacy over time. Clearly, the administration of a single cytokine or a single
cytokine-blocking agent is insufficient for achieving long-term pro-angiogenic or
anti-angiogenic effects.
Future research must focus on refining the characterization of angiogenesis at
the molecular, cellular, tissue, and organ levels. A detailed understanding of
multiple cell signaling pathways will be necessary to the development of effective
therapeutics, and may suggest novel avenues for therapy. Further, the properties of
various cellular populations must be delineated, both in healthy and diseased
tissues. For example, endothelial cells exhibit specific dysfunctions in both
coronary artery disease and cancer; such abnormalities will most certainly influ-
ence cellular responses to therapy. The roles of cellular migration and cellular
mechanics must be investigated, along with the interactions of cells with the
extracellular matrix.
In regard to drug development, new methods for drug delivery which enable
cell and tissue targeting, as well as controlled release, will improve therapeutic
efficacy. The spatial and temporal delivery of pro-angiogenic and anti-angiogenic
agents must be optimized. Finally, it is likely that a combination of agents will be
required to achieve a lasting therapeutic effect. An urgent clinical need remains for
novel pro-angiogenic and anti-angiogenic approaches. With continued research
advances in angiogenesis, therapeutic strategies for angiogenesis will continually
improve, and progressively alleviate the global burden of disease.
Acknowledgments The author thanks the faculty and students of the Harvard University School
of Engineering and Applied Sciences for providing inspiration and support of innovative work in
biomedical engineering.
References
1. Folkman, J.: Tumor angiogenesis: therapeutic implications. N. Engl. J. Med. 285(21),
1182-1186 (1971)
2. Carmeliet, P.: Angiogenesis in health and disease. Nat. Med. 9(6), 653-660 (2003)
3. Bhadada, S.V., Goyal, B.R., Patel, M.M.: Angiogenic targets for potential disorders. Fundam.
Clin. Pharmacol. 25(1), 29-47 (2010)
4. Simons, M.: Angiogenesis, arteriogenesis, and diabetes: paradigm reassessed? J. Am. Coll.
Cardiol. 46(5), 835-837 (2005)
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