Thomas-Virnig Christina L, Allen-Hoffmann B Lynn
Department of Pathology and Laboratory Medicine, University of Wisconsin , Madison, Wisconsin.
Adv Wound Care (New Rochelle). 2012 Apr;1(2):88-94. doi: 10.1089/wound.2011.0338.
Complex skin defects resulting from acute skin trauma and chronic, nonhealing wounds are life-threatening injuries. Infection is one of the most common obstacles to the healing of these types of wounds. Host defense peptides (HDPs) possessing a broad spectrum of activity against microorganisms and serving as innate immune modulators have emerged as potential treatment strategies for infected wounds.
The increase in multidrug-resistant clinical bacterial isolates highlights the need for new and innovative anti-infective therapies for the treatment of both acute and chronic skin wounds.
BASIC/CLINICAL SCIENCE: To address the critical need for new therapeutic options to reduce infection and improve wound healing, a bioengineered skin substitute (BSS) tissue has been created to act as an anti-infective living human skin tissue that provides enhanced expression of the endogenous HDP, cathelicidin. To generate a BSS exhibiting these antimicrobial properties, the clinically tested NIKS progenitor cells were employed to provide a source of genetically uniform, nontumorigenic, pathogen-free human keratinocytes that are amenable to genetic engineering using nonviral means.
Pathogenic bacterial strains are increasingly developing antibiotic resistance, thereby forcing the clinician to use potent antibiotics with deleterious effects on keratinocyte viability and migration. Therefore, an urgent need exists for new wound therapies that can circumvent many of the problems associated with current antibiotic treatments.
Enhanced expression of cathelicidin in a genetically engineered human BSS has been shown to inhibit the bacterial growth of a multidrug-resistant clinical strain of , creating a new and innovative therapeutic option for combating these debilitating wound infections while also promoting healing.
急性皮肤创伤和慢性难愈合伤口导致的复杂皮肤缺损是危及生命的损伤。感染是这类伤口愈合最常见的障碍之一。具有广泛抗微生物活性并作为先天性免疫调节剂的宿主防御肽（HDPs）已成为感染性伤口潜在的治疗策略。
多重耐药临床细菌分离株的增加凸显了对治疗急慢性皮肤伤口的新型创新抗感染疗法的需求。
基础/临床科学：为满足减少感染和改善伤口愈合的新治疗选择的迫切需求，已创建一种生物工程皮肤替代物（BSS）组织，作为一种抗感染的活性人体皮肤组织，可增强内源性HDP（cathelicidin）的表达。为生成具有这些抗菌特性的BSS，采用经临床测试的NIKS祖细胞，以提供遗传上一致、无致瘤性、无病原体的人类角质形成细胞来源，这些细胞适合使用非病毒方法进行基因工程改造。
致病细菌菌株越来越多地产生抗生素耐药性，从而迫使临床医生使用对角质形成细胞活力和迁移有有害影响的强效抗生素。因此，迫切需要新的伤口治疗方法来规避与当前抗生素治疗相关的许多问题。
基因工程改造的人类BSS中cathelicidin表达增强已被证明可抑制多重耐药临床菌株的细菌生长，为对抗这些使人衰弱的伤口感染同时促进愈合创造了一种新的创新治疗选择。
