Clinical applications of heparin-binding growth factors.

The family of HBGFs represents one of the most important families of mediators yet described, capable of inducing mesenchymal cell proliferation and differentiation, tissue regeneration, morphogenesis, and neovascularization, and it is clear their clinical potential is enormous. While some obvious applications of HBGFs, such as in wound healing and seeding of vascular prostheses, are already being examined in detail, the realization of their full clinical potential will require the co-ordinated efforts of many laboratories in a wide spectrum of fields. A better understanding is needed of the pathophysiological roles of HBGFs in vivo. For example, if abnormal expression of HBGFs is the cause of certain pathologies characterized by abnormal vascularization, the clinical potential of HBGF antagonists as inhibitors of angiogenesis will be considerable. A better understanding is also needed of the relationship between HBGF structure and function, susceptibility to proteolysis, in-vivo stability, and synergism with other biological response modifiers. In addition, many clinical applications will be limited by our ability to target HBGFs to selected sites in the body, while others will be limited by undesirable side-effects. Indeed, the minimization of such side-effects may rapidly become a central issue in the in-vivo use of HBGFs. For example, the presence of HBGFs in ocular tissues, their role in phototransduction, their ability to induce neovascularization, and the clear link between abnormal ocular neovascularization and blindness, suggest that the eye may be an organ particularly sensitive to local changes in HBGF levels. Finally, HBGFs will almost certainly have extremely potent immunoregulatory effects. Nevertheless, the application of HBGFs in a variety of clinical situations should lead to many innovative therapeutic advances.