Ameliorated healing of biliary anastomosis by autologous adipose-derived stem cell sheets

Introduction: Cell sheets consisting of adipose -derived stem cells (ADSCs) have been reported to be effective for wound healing. We conducted this study to clarify the ef ficacy of ADSC sheets in wound healing at the duct-to-duct biliary anastomotic site in pigs. Methods: Eleven female pigs (20-25 kg) were divided into two groups: biliary anastomosis with an ADSC sheet (n = 6) or without an ADSC sheet (n = 5). To follow the transplanted ADSCs, PKH26GL- labeled sheets were used in one of the ADSC pigs. Two weeks prior to laparotomy, ADSCs were iso- lated from the lower abdominal subcutaneous adipose tissue. After three passages, ADSCs were seeded on temperature-responsive culture dishes and collected as cell sheets. ADSC sheets were gently trans- planted on the anastomotic site. We evaluated specimens by PKH26GL labeling, macroscopic changes, in filtration of in flammatory cells, and collagen content. Results: Labeled ADSCs remained around the bile duct wall. In the no-ADSC group, more adhesion developed at the hepatic hilum as observed during relaparotomy. Histopathological examination showed that the diameter and cross-sectional area of the bile duct wall were decreased in the ADSC group. In the no-ADSC group, a large number of in flammatory cells and more collagen fibers were identi fied in the bile duct wall. Conclusions: The present study demonstrated that autologous ADSC sheet transplantation reduced hypertrophic changes in the bile duct wall at the anastomotic site. A long-term follow-up is required to evaluate the ef ficacy of this mechanism in prevention of biliary anastomotic strictures. (C) 2020, The Japanese Society for Regenerative Medicine. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/ 4.0/).