Oral administration of conditioned medium obtained from mesenchymal stem cell culture prevents subsequent stricture formation after esophageal submucosal dissection in pigs
Oral administration of conditioned medium obtained from mesenchymal stem cell culture prevents subsequent stricture formation after esophageal submucosal dissection in pigs
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DOI：
10.1016/j.gie.2017.01.024
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发表时间：
2017-09-01
影响因子：
7.7
通讯作者：
Sakamoto, Naoya
中科院分区：
文献类型：
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作者：
Mizushima, Takeshi;Ohnishi, Shunsuke;Sakamoto, Naoya
背景和目标：食管癌的内镜粘膜下剥离术（ESD）在切除食管周长超过四分之三时常引起术后狭窄。间充质干细胞是再生医学中有价值的细胞来源，据报道从间充质干细胞获得的条件培养基（CM）抑制炎症。在这项研究中，我们评估是否CM可以防止食管狭窄后ESD。方法：我们切除了半周猪食管ESD。我们通过与5%羧甲基纤维素混合来制备CM凝胶，并在ESD后立即和第8天和第15天（每周CM组）将其内窥镜下应用于伤口床上，或从第1天至第4天口服施用（每日CM组）。我们还在ESD后立即将曲安奈德注射到剩余的粘膜下层（类固醇组）。结果：每周和每日CM组和类固醇组在第22天的狭窄率均显著低于对照组。此外，CM显着衰减的数量激活的肌成纤维细胞和纤维厚度在第22天。CM凝胶可明显减少中性粒细胞和巨噬细胞浸润，并能抑制中性粒细胞和巨噬细胞浸润后肌成纤维细胞的活化和纤维化，从而预防食管狭窄的形成。CM凝胶的口服给药是预防ESD后狭窄的有前景的治疗方法。
Background and Aims: Endoscopic submucosal dissection (ESD) for esophageal cancer often causes postoperative stricture when more than three fourths of the circumference of the esophagus is dissected. Mesenchymal stem cells are a valuable cell source in regenerative medicine, and conditioned medium (CM) obtained from mesenchymal stem cells reportedly inhibits inflammation. In this study we evaluated whether CM could prevent esophageal stricture after ESD.Methods: We resected a semi-circumference of pig esophagus by ESD. We prepared CM gel by mixing with 5% carboxymethyl cellulose and endoscopically applied it onto the wound bed immediately after ESD and on days 8 and 15 (weekly CM group) or administered it orally from days 1 to 4 (daily CM group). We also injected triamcinolone acetonide into the remaining submucosa immediately after ESD (steroid group). We killed the pigs on day 8 or day 22 to measure the stricture rate and to perform histologic analysis.Results: Stricture rate in weekly and daily CM groups and steroid groups were significantly lower than in the control group on day 22. Moreover, CM significantly attenuated the number of activated myofibroblasts and fiber thickness on day 22. CM also significantly decreased the infiltration of neutrophils and macrophages compared with the control group on day 8.Conclusions: CM gel prevents esophageal stricture formation by suppressing myofibroblast activation and fibrosis after the infiltration of neutrophils and macrophages. Oral administration of CM gel is a promising treatment for the prevention of post-ESD stricture.