Adipose-Derived Stem Cells Prevent Anastomotic Leak: A Porcine Ischemic Esophagectomy Model.

Abstract

Introduction: Esophagectomy is a lifesaving procedure plagued by an anastomotic leak rate of 11%-35%. Ischemia is widely accepted to be the most significant risk factor for anastomotic leak. We hypothesized that the injection of adipose-derived stem cells (ASCs) into an ischemic esophagogastric anastomosis would prevent leakage.

Methods: We developed a leaking ischemic esophagogastric anastomosis model in pigs using indocyanine green and the Elevision device to quantify perfusion. Anastomoses created using a gastric conduit with a relative perfusion of 50%-60% produced an anastomosis that consistently leaked (n = 3) compared to nonischemic controls (n = 3). We then injected either human (n = 2) or porcine (n = 2) ASCs around an ischemic anastomosis. We analyzed clinical outcomes including postoperative sepsis, weight loss, and disruption of the anastomosis and histopathology as well as immunohistochemistry.

Results: All of the ischemic controls (3/3, 100%), as well as the xenograft human ASC-injected experimental group (2/2, 100%), became septic postoperatively and were found to have an anastomotic breakdown or disruption on necropsy. However, in the porcine allograft ASC-injected experimental group, the animals did well, with none of the subjects experiencing postoperative sepsis, and none were found to have disrupted anastomoses on necropsy. Histopathology revealed improved apposition of the anastomosis and immunohistochemistry revealed improved epithelization and submucosal fibrosis of the porcine ASC group compared to ischemic and human ASC groups.

Conclusions: Allogenic ASCs prevented anastomotic leakage of esophagogastric anastomosis in a porcine ischemic esophagectomy model.