LeGrand E K
The R.W. Johnson Pharmaceutical Research Institute, Raritan, New Jersey 08869, USA.
Am J Surg. 1998 Aug;176(2A Suppl):48S-54S. doi: 10.1016/s0002-9610(98)00177-9.
Advances in molecular biology have made possible the production of highly purified recombinant human proteins, and recombinant human growth factors have emerged as potential therapeutic wound healing agents. Becaplermin (recombinant human platelet-derived growth factor-BB [rhPDGF-BB]) quickly emerged as one of the leading candidates for clinical trials. Before the expected therapeutic potential of rhPDGF-BB and other growth factors could be realized, a number of concerns had to be addressed (eg, would growth factors show effects in normal animals, what parameters of wound healing would be affected, and would quality of healed wounds be normal?). In animal models, rhPDGF-BB demonstrated wound healing activity, predominantly by enhancing the formation of granulation tissue, but it was not known whether this effect on granulation tissue would translate into enhanced healing of chronic skin ulcers in humans. The objective of this article is to review how the study of rhPDGF-BB in animal wound healing models has assisted in addressing the potential clinical utility of rhPDGF-BB. Results of animal studies are summarized, and the advantages and limitations of the animal models are discussed.
分子生物学的进展使生产高度纯化的重组人蛋白成为可能，重组人生长因子已成为潜在的治疗伤口愈合的药物。贝卡普勒明（重组人血小板衍生生长因子-BB [rhPDGF-BB]）迅速成为临床试验的主要候选药物之一。在rhPDGF-BB和其他生长因子的预期治疗潜力得以实现之前，必须解决一些问题（例如，生长因子在正常动物中会显示出效果吗？伤口愈合的哪些参数会受到影响？愈合伤口的质量会正常吗？）。在动物模型中，rhPDGF-BB表现出伤口愈合活性，主要是通过增强肉芽组织的形成，但尚不清楚这种对肉芽组织的作用是否会转化为人类慢性皮肤溃疡愈合的增强。本文的目的是回顾在动物伤口愈合模型中对rhPDGF-BB的研究如何有助于探讨rhPDGF-BB的潜在临床应用。总结了动物研究的结果，并讨论了动物模型的优缺点。
