Sun Li, Xie Zhuojun, Kuang Mei, Penn Marc, Damaser Margot S, Zutshi Massarat
1 Department of Colorectal Surgery, Cleveland Clinic, Cleveland, Ohio 2 Department of Biomedical Engineering, Cleveland Clinic, Cleveland, Ohio 3 Summa Cardiovascular Institute, Akron, Ohio 4 Glickman Urological & Kidney Institute, Cleveland Clinic, Cleveland, Ohio 5 Advanced Platform Technology Center, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, Ohio.
Dis Colon Rectum. 2017 Apr;60(4):416-425. doi: 10.1097/DCR.0000000000000783.
Healing of an anal sphincter defect at a time distant from injury is a challenge.
We aimed to investigate whether re-establishing stem cell homing at the site of an anal sphincter defect when cytokine expression has declined using a plasmid engineered to express stromal derived factor 1 with or without mesenchymal stem cells can improve anatomic and functional outcome.
This was a randomized animal study.
Thirty-two female age- and weight-matched Sprague Dawley rats underwent 50% excision of the anal sphincter complex. Three weeks after injury, 4 interventions were randomly allocated (n = 8), including no intervention, 100-μg plasmid, plasmid and 800,000 cells, and plasmid with a gelatin scaffold mixed with cells.
The differences in anal sphincter resting pressures just before and 4 weeks after intervention were used for functional analysis. Histology was analyzed using Masson staining. One-way ANOVA followed by the Tukey post hoc test was used for pressure and histological analysis.
All 3 of the intervention groups had a significantly greater change in resting pressure (plasmid p = 0.009; plasmid + cells p = 0.047; plasmid + cells in scaffold p = 0.009) compared with the control group. The plasmid-with-cells group showed increased organization of muscle architecture and increased muscle percentage, whereas the control group showed disorganized architecture at the site of the defect. Histological quantification revealed significantly more muscle at the site of defect in the plasmid-plus-cells group compared with the control group, which had the least muscle. Quantification of connective tissue revealed significantly less fibrosis at the site of defect in the plasmid and plasmid-plus-cells groups compared with the control group.
Midterm evaluation and muscle morphology were not defined.
At this midterm follow-up, local delivery of a stromal derived factor 1 plasmid with or without local mesenchymal stem cells enhanced anal sphincter muscle regeneration long after an anal sphincter injury, thereby improving functional outcome. See Video Abstract at http://links.lww.com/DCR/A324.
在远离损伤时间点修复肛门括约肌缺损是一项挑战。
我们旨在研究当细胞因子表达下降时，使用经基因工程改造以表达基质衍生因子1的质粒，无论有无间充质干细胞，在肛门括约肌缺损部位重新建立干细胞归巢是否能改善解剖和功能结局。
这是一项随机动物研究。
32只年龄和体重匹配的雌性Sprague Dawley大鼠接受肛门括约肌复合体50%切除术。损伤3周后，随机分配4种干预措施（n = 8），包括不干预、100μg质粒、质粒加80万细胞，以及质粒与明胶支架混合加细胞。
干预前和干预后4周的肛门括约肌静息压力差异用于功能分析。使用Masson染色进行组织学分析。采用单因素方差分析及Tukey事后检验进行压力和组织学分析。
与对照组相比，所有3个干预组的静息压力变化均显著更大（质粒组p = 0.009；质粒 + 细胞组p = 0.047；支架中质粒 + 细胞组p = 0.009）。质粒加细胞组显示肌肉结构的组织化增加和肌肉百分比增加，而对照组在缺损部位显示结构紊乱。组织学定量显示，与肌肉最少的对照组相比，质粒加细胞组缺损部位的肌肉显著更多。结缔组织定量显示，与对照组相比，质粒组和质粒加细胞组缺损部位的纤维化显著更少。
未定义中期评估和肌肉形态。
在本次中期随访中，局部递送基质衍生因子1质粒，无论有无局部间充质干细胞，在肛门括约肌损伤很久之后均可增强肛门括约肌肌肉再生，从而改善功能结局。见视频摘要：http://links.lww.com/DCR/A324 。
