Wolfort S F, Reiken S R, Berthiaume F, Tompkins R G, Yarmush M L
Surgical Services, Massachusetts General Hospital, Boston, 02114, USA.
J Surg Res. 1996 Apr;62(1):17-22. doi: 10.1006/jsre.1996.0166.
Hypertrophic scar is marked by excess collagen accumulation secondary to an increased vascularization response in the scar and an increase in fibroblast cell density. It is currently the most debilitating long-term complication of the surviving burn patient, and at present, there is no routinely effective form of therapy. In this study, we investigated the potential use of antibody-targeted photolysis (ATPL) in treating hypertrophic scars. An immunoconjugate consisting of a photosensitizer (Sn-chlorin e6) linked to a monoclonal antibody that binds to human myofibroblasts (PR2D3) was prepared, which in response to photoactivation produces singlet oxygen in close proximity to the target cell surface. The model used for these studies consisted of 1-mm 3 human hypertrophic scar tissue implants in athymic mice. These implants increase approximately 20-fold in volume over a period of 15 days. Four days after implantation immunoconjugate was injected directly into scar implants allowed to diffuse throughout for 24 hr before implants were illuminated with laser light at 630 nm (120 J/cm 2). ATPL treatment caused a significant reduction in total growth compared to the untreated controls (P < 0.05). No effect was observed when an irrelevant conjugate (anti-Pseudomonas aeruginosa) was used. Histological examination of the ATPL-treated implants 24 hr post-ATPL revealed the presence of a large number of lipid droplets indicative of massive cell damage and infiltration by mononuclear cells and neutrophils.
增生性瘢痕的特征是瘢痕中血管生成反应增强以及成纤维细胞密度增加导致胶原蛋白过度积累。它是目前烧伤幸存者最使人衰弱的长期并发症，目前尚无常规有效的治疗方法。在本研究中，我们研究了抗体靶向光解（ATPL）在治疗增生性瘢痕中的潜在用途。制备了一种免疫缀合物，其由与结合人肌成纤维细胞的单克隆抗体（PR2D3）连接的光敏剂（锡-二氢卟吩e6）组成，该免疫缀合物在光激活后会在靶细胞表面附近产生单线态氧。用于这些研究的模型由无胸腺小鼠体内1立方毫米的人增生性瘢痕组织植入物组成。这些植入物在15天内体积增加约20倍。植入后4天，将免疫缀合物直接注射到瘢痕植入物中，使其扩散24小时，然后用630纳米的激光照射植入物（120焦/平方厘米）。与未治疗的对照组相比，ATPL治疗导致总生长显著降低（P<0.05）。使用无关缀合物（抗铜绿假单胞菌）时未观察到效果。ATPL治疗后24小时对经ATPL处理的植入物进行组织学检查，发现存在大量脂滴，表明大量细胞损伤以及单核细胞和中性粒细胞浸润。
