Department of Surgery, Mayo Clinic, Rochester, Minnesota, USA.
Department of Surgery, Mayo Clinic, Rochester, Minnesota, USA; Department for General, Visceral and Vascular Surgery, University Hospital Jena, Jena, Germany.
Cytotherapy. 2023 May;25(5):483-489. doi: 10.1016/j.jcyt.2023.01.014. Epub 2023 Feb 25.
Roux en y anastomosis is a preferred method of biliary reconstruction in liver transplantation that involves living donors or pediatric patients. However, biliary stricture is a frequent and serious complication, accounting for up to 40% of biliary complications in these patients. Previously, we demonstrated that extraluminal delivery of adipose-derived (AD) mesenchymal stromal cells (MSCs) decreased peri-biliary fibrosis and increased neo-angiogenesis in a porcine model of duct-to-duct biliary anastomosis. In this study, we used a porcine model of Roux en y anastomosis to evaluate the beneficial impact of a novel intraluminal MSC delivery system.
Nine animals were divided into three groups: no stent (group 1), bare stent (group 2) and stent coated with AD-MSCs (group 3). All animals underwent cholecystectomy with roux en y choledochojejunostomy. Two animals per group were followed for 4 weeks and one animal per group was followed for 8 weeks. Cholangiograms and blood were sampled at baseline and the end of study. Biliary tissue was collected and examined by Masson trichrome staining and immunohistochemical staining for MSC markers (CD34 and CD44) and for neo-angiogenesis (CD31).
Two of three animals in group 1 developed an anastomotic site stricture. No strictures were observed in the animals of group 2 or group 3. CD34 and CD44 staining showed that AD-MSCs engrafted successfully at the anastomotic site by intraluminal delivery (group 3). Furthermore, biliary tissue from group 3 showed significantly less fibrosis and increased angiogenesis compared with the other groups.
Intraluminal delivery of AD-MSCs resulted in successful biliary engraftment of AD-MSCs as well as reduced peri-biliary fibrosis and increased neo-angiogenesis.
Roux-en-Y 吻合术是肝移植中胆管重建的首选方法，适用于活体供体或儿科患者。然而，胆管狭窄是一种常见且严重的并发症，在这些患者中占胆管并发症的 40%。先前，我们证明了外腔递送脂肪来源（AD）间充质基质细胞（MSCs）可减少胆管吻合术后胆管周围纤维化并增加新生血管形成。在本研究中，我们使用了 Roux-en-Y 吻合术的猪模型来评估新型腔内 MSC 递送系统的有益影响。
将 9 只动物分为 3 组：无支架组（第 1 组）、裸支架组（第 2 组）和 AD-MSCs 涂层支架组（第 3 组）。所有动物均行胆囊切除术和 Roux-en-Y 胆肠吻合术。每组 2 只动物进行 4 周随访，每组 1 只动物进行 8 周随访。在基线和研究结束时采集胆管造影和血液样本。采集胆管组织进行 Masson 三色染色和 MSC 标志物（CD34 和 CD44）和新生血管形成（CD31）的免疫组织化学染色。
第 1 组的 3 只动物中有 2 只发生吻合口狭窄。第 2 组和第 3 组的动物均未观察到狭窄。CD34 和 CD44 染色显示，通过腔内递送成功将 AD-MSCs 移植到吻合部位（第 3 组）。此外，与其他组相比，第 3 组的胆管组织纤维化明显减少，新生血管形成增加。
腔内递送 AD-MSCs 可成功实现 AD-MSCs 的胆管移植，并减少胆管周围纤维化和增加新生血管形成。
