Liechty K W, Nesbit M, Herlyn M, Radu A, Adzick N S, Crombleholme T M
The Children's Institute for Surgical Science at The Children's Hopsital of Philadelphia, The University of Pennsylvania School of Medicine 19104, USA.
J Invest Dermatol. 1999 Sep;113(3):375-83. doi: 10.1046/j.1523-1747.1999.00705.x.
Chronic wounds represent a major clinical problem with significant morbidity and healthcare expenditures, but no effective therapies. Topical platelet-derived growth factor-BB trials have required large and repeated doses to achieve only a modest effect. We examined the ability of an adenovirus containing the platelet-derived growth factor-B transgene to improve the rate of wound healing through induction of platelet-derived growth factor-B overexpression in cells participating in the wound healing response. We treated excisional wounds in the ischemic rabbit ear, which have a 60% delay in healing, with vehicle, 106, or 108 plaque-forming units of an adenovirus containing the platelet-derived growth factor-B per wound (n = 19). At 7 d this resulted in a decrease in the epithelial gap from 3.4 +/- 1 mm (mean +/- SD) in vehicle-treated wounds to 1.9 +/- 1.8 mm (mean +/- SD, p < 0.05) when treated with 106 plaque-forming units of an adenovirus containing the platelet-derived growth factor-B, and 0.7 +/- 1.1 mm (mean +/- SD, p < 0.001) when treated with 108 plaque-forming units of an adenovirus containing the platelet-derived growth factor-B. Ischemic excisional wounds treated with 108 plaque-forming units of an adenovirus containing the platelet-derived growth factor-B even healed more rapidly than non-ischemic excisional wounds treated with vehicle (p < 0.05). In contrast, 5 microg of platelet-derived growth factor-BB protein (n = 2) resulted in only modest granulation tissue at the margin, but no significant differences in epithelial gap (3 +/- 0.6 mm, mean +/- SD). Plaque-forming units (106 or 108) of an adenovirus containing the beta-galactosidase transgene (n = 4) impaired wound re-epithelialization with an epithelial gap of 5.11 +/- 0.69 mm, mean +/- SD, p < 0.004, and 3.8 +/- 0.57 mm, mean +/- SD, p < 0.07, respectively. Adenoviral-mediated gene transfer of platelet-derived growth factor-B overcame the ischemic defect in wound healing and offers promise in the treatment of chronic nonhealing wounds. The vulnerary effects of platelet-derived growth factor-B overexpression were sufficient to overcome the adverse effects of the adenovirus or transgene on wound healing.
慢性伤口是一个重大的临床问题，会导致严重的发病率和医疗费用支出，却没有有效的治疗方法。局部应用血小板衍生生长因子-BB的试验需要大剂量且反复给药才能产生适度效果。我们研究了一种携带血小板衍生生长因子-B转基因的腺病毒，通过诱导参与伤口愈合反应的细胞中血小板衍生生长因子-B过表达来提高伤口愈合速度的能力。我们用赋形剂、每伤口106或108个空斑形成单位的携带血小板衍生生长因子-B的腺病毒治疗缺血兔耳的切除伤口，这些伤口愈合延迟60%（n = 19）。在第7天，这导致上皮间隙从赋形剂处理伤口的3.4±1毫米（平均值±标准差），在用106个空斑形成单位的携带血小板衍生生长因子-B的腺病毒处理时降至1.9±1.8毫米（平均值±标准差，p < 0.05），在用108个空斑形成单位的携带血小板衍生生长因子-B的腺病毒处理时降至0.7±1.1毫米（平均值±标准差，p < 0.001）。用108个空斑形成单位的携带血小板衍生生长因子-B的腺病毒处理的缺血切除伤口甚至比用赋形剂处理的非缺血切除伤口愈合更快（p < 0.05）。相比之下，5微克血小板衍生生长因子-BB蛋白（n = 2）仅在边缘产生适度的肉芽组织，但上皮间隙无显著差异（3±0.6毫米，平均值±标准差）。含有β-半乳糖苷酶转基因的腺病毒的空斑形成单位（106或108）（n = 4）损害伤口再上皮化，上皮间隙分别为5.11±0.
