Tissue Eng Regen Med.  2022 Apr;19(2):403-415. 10.1007/s13770-021-00421-5.

Application of Bone Marrow Mesenchymal Stem Cells Effectively Eliminates Endotoxemia to Protect Rat from Acute Liver Failure Induced by Thioacetamide

Affiliations
  • 1Department of Gastroenterology, The Second Affiliated Hospital of Kunming Medical University, 374 Dianmian Avenue, Kunming 650106, Yunnan, China
  • 2Institute of Medical Biology, Chinese Academy of Medical Sciences, 935 Jiaoling Road, Kunming 650031, Yunnan, China
  • 3Department of Gastroenterology, West China Hospital, Sichuan University, 37 Guoxue lane, Chengdu 610044, Sichuan, China

Abstract

BACKGROUND
Endotoxemia is related to worse clinical outcomes in acute liver failure (ALF), but its management remains unsatisfactory. In this study, we aimed to assess whether the application of bone marrow mesenchymal stem cells (BMSCs) could eliminate endotoxemia and protect rats against ALF induced by thioacetamide (TAA).
METHODS
BMSCs were isolated from rats and identified by the specific morphology, differentiation potential, and surface markers. The optimal dose of TAA for this study was explored and TAA-induced ALF rats were randomized to three groups: the normal control group (Saline), ALF group (TAA + Saline), and BMSCs-treated group (TAA + BMSCs). The intestinal migration and differentiation of BMSCs was tracked in vivo, and intestinal permeability, endotoxin and inflammatory cytokines, histology, and mortality were analyzed. Moreover, we added the inhibitor of the PI3K/AKT/ mTOR signaling pathway into the co-culture system of BMSCs with enterocytes and then performed CK and Villin expression experiments to assess the role of PI3K/AKT/mTOR signal pathway in the intestinal differentiation of BMSCs.
RESULTS
BMSCs migrated to the intestinal injury sites and differentiated into enterocytes, intestinal permeability was decreased compared with the ALF group. The higher expression of endotoxin and inflammatory cytokines were reversed after BMSCs transplantation in rats with ALF. Mortality and intestinal lesion were significantly decreased. Blocking the PI3K/AKT/mTOR signal pathway inhibited BMSCs’ intestinal differentiation in vitro.
CONCLUSION
BMSCs can eliminate endotoxemia and reduce mortality in rats with ALF, and the PI3K/AKT/mTOR signal pathway is involved in intestinal differentiation. BMSCs transplantation could be a potential candidate for the treatment of endotoxemia in ALF.

Keyword

Bone marrow mesenchymal stem cells; Acute liver failure; Endotoxemia; Differentiation; PI3K
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