Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Department of Gastrointestinal Surgery, Tokyo Medical University, Shinjuku-ku, Tokyo, Japan.
Sci Rep. 2019 May 9;9(1):7149. doi: 10.1038/s41598-019-43734-1.
Adhesions are a very common complication in the abdominal surgery. Animal studies and human trials have evaluated strategies designed to reduce and prevent postsurgical adhesions but few have an evidence base that justifies routine use. A strategy to prevent adhesions effectively remains an urgent need. We studied a reproducible model of intra-peritoneal adhesion formation in rats using laparotomy with several peritoneal sutures to produce the adhesions. Here we show that entraining endogenous stem cells into injury sites using the combined effect of AMD3100 and low-dose FK-506 (AF) can reduce the adhesion score significantly and abolish peritoneal adhesions in 45% of animals in a rat model of severe postsurgical intra-abdominal adhesions, compared with saline controls. Searching for mechanisms, we found AF treatment dramatically increased SDF-1 expressing cells, HGF expressing Ym1+ M2 macrophages and CD133+ stem cells in the injury sites of peritoneal surface at day 5 post-operation. Our results demonstrate that medically induced recruitment of autologous stem cells using AF significantly reduced postsurgical intra-abdominal adhesions. These findings suggest a novel effective therapeutic approach to preventing adhesions in patients.
粘连是腹部手术中非常常见的并发症。动物研究和人体试验已经评估了旨在减少和预防术后粘连的策略，但很少有证据支持常规使用。一种有效的预防粘连的策略仍然是当务之急。我们使用剖腹术和几个腹膜缝线在大鼠中研究了一种可重复的腹膜内粘连形成模型，以产生粘连。在这里，我们显示使用 AMD3100 和低剂量 FK-506（AF）的组合效应将内源性干细胞引入损伤部位，可以显著降低粘连评分，并在大鼠严重术后腹腔内粘连模型中使 45%的动物消除腹膜粘连，与生理盐水对照组相比。在寻找机制的过程中，我们发现在术后第 5 天，AF 处理显著增加了损伤部位的 SDF-1 表达细胞、表达 HGF 的 Ym1+M2 巨噬细胞和 CD133+干细胞。我们的结果表明，使用 AF 诱导内源性干细胞的医学招募显著减少了术后腹腔内粘连。这些发现表明，这是一种预防患者粘连的新有效治疗方法。
