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Liver Transpl. 2019 Nov 19. doi: 10.1002/lt.25682. [Epub ahead of print]

Autologous Adipose Tissue-Derived Mesenchymal Stem Cells Introduced by Biliary Stents or Local Immersion in Porcine Bile Duct Anastomoses.

Author information

1
Department of Surgery, Mayo Clinic and Foundation, Rochester, MN.
2
Chongqing University Cancer Hospital, Chongqing, China.
3
Department of Surgery, Yonsei University, Seoul, Korea.
4
Gastroenterology Research Unit, Mayo Clinic and Foundation, Rochester, MN.
5
Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA.
6
Division of Gastroenterology and Hepatology, Mayo Clinic and Foundation, Rochester, MN.
7
Department of Laboratory Medicine and Pathology, Mayo Clinic and Foundation, Rochester, MN.
8
William J. von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic and Foundation, Rochester, MN.

Abstract

BACKGROUND:

Biliary complications (strictures and leaks), represent major limitations in living-donor liver transplantation. Mesenchymal stem cells (MSC) are a promising modality to prevent biliary complications owing to immunosuppressive and angiogenic properties. Our goal was to evaluate the safety of adipose-derived MSC delivery to biliary anastomoses in a porcine model. Secondary objectives were defining the optimal method of delivery (intraluminal vs extraluminal) and to investigate MSC engraftment, angiogenesis, and fibrosis.

METHODS:

Pigs were divided into three groups. Animals underwent adipose collection, MSC isolation, and expansion. Two weeks later, animals underwent bile duct transection, re-anastomosis, and stent insertion. Group 1 received plastic stents wrapped in unseeded vicryl mesh; Group 2 received stents wrapped in MSC-seeded mesh; Group 3 received unwrapped stents with the anastomosis immersed in an MSC-suspension. Animals were sacrificed one month after stent insertion when cholangiograms and biliary tissue were obtained. Serum was collected for liver biochemistries. Tissue was used for hematoxylin/eosin/trichrome staining and immunohistochemistry for MSC markers (CD44 and CD34) and a marker of neo-angiogenesis (CD31).

RESULTS:

There were no intra-operative complications. One pig died on post-operative day three due to acute cholangitis. All others recovered without complications. Cholangiography demonstrated no biliary leaks and minimal luminal narrowing. Surviving animals exhibited no symptoms, abnormal liver biochemistries, or clinically-significant biliary stricturing. Group 3 showed significantly greater CD44 and CD34 staining, indicating MSC engraftment. Fibrosis was reduced at the anastomotic site in Group 3 based on trichrome stain. CD31 staining of Group 3 was more pronounced, supporting enhanced neo-angiogenesis.

CONCLUSION:

Adipose-derived MSC were safely applied to biliary anastomoses. MSC were locally engrafted within the bile duct and may have beneficial effects in terms of fibrosis and angiogenesis.

KEYWORDS:

Stricture; angiogenesis; fibrosis; mesh; vicryl

PMID:
31742878
DOI:
10.1002/lt.25682

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