Adipose Stem Cell Therapy Mitigates Chronic Pancreatitis via Differentiation into Acinar-like Cells in Mice.

Abstract

The objective of this study was to assess the capacity of adipose-derived mesenchymal stem cells (ASCs) to mitigate disease progression in an experimental chronic pancreatitis mouse model. Chronic pancreatitis (CP) was induced in C57BL/6 mice by repeated ethanol and cerulein injection, and mice were then infused with 4 × 105 or 1 × 106 GFP+ ASCs. Pancreas morphology, fibrosis, inflammation, and presence of GFP+ ASCs in pancreases were assessed 2 weeks after treatment. We found that ASC infusion attenuated pancreatic damage, preserved pancreas morphology, and reduced pancreatic fibrosis and cell death. GFP+ ASCs migrated to pancreas and differentiated into amylase+ cells. In further confirmation of the plasticity of ASCs, ASCs co-cultured with acinar cells in a Transwell system differentiated into amylase+ cells with increased expression of acinar cell-specific genes including amylase and chymoB1. Furthermore, culture of acinar or pancreatic stellate cell lines in ASC-conditioned medium attenuated ethanol and cerulein-induced pro-inflammatory cytokine production in vitro. Our data show that a single intravenous injection of ASCs ameliorated CP progression, likely by directly differentiating into acinar-like cells and by suppressing inflammation, fibrosis, and pancreatic tissue damage. These results suggest that ASC cell therapy has the potential to be a valuable treatment for patients with pancreatitis.

• Authors: Zhen Sun, Wenyu Gou, Do-Sung Kim, Xiao Dong, Charlie Strange, Yu Tan, David B Adams, Hongjun Wang
• Journal: Molecular therapy : the journal of the American Society of Gene Therapy (Mol Ther) Vol. 25 Issue 11 Pg. 2490-2501 (11 01 2017) ISSN: 1525-0024 [Electronic] United States
• PMID: 28784560 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

Chemical References

• Culture Media, Conditioned
• Interleukin-6
• Tumor Necrosis Factor-alpha
• interleukin-6, mouse
• Green Fluorescent Proteins
• Ethanol
• Ceruletide
• Amylases

Topics

• Acinar Cells (cytology, drug effects, metabolism)
• Adipose Tissue (cytology, metabolism)
• Amylases (genetics, metabolism)
• Animals
• Cell Differentiation
• Cell Movement
• Cell- and Tissue-Based Therapy (methods)
• Ceruletide (administration & dosage)
• Coculture Techniques
• Culture Media, Conditioned (pharmacology)
• Ethanol (administration & dosage)
• Gene Expression
• Genes, Reporter
• Green Fluorescent Proteins (genetics, metabolism)
• Humans
• Interleukin-6 (antagonists & inhibitors, genetics, metabolism)
• Male
• Mesenchymal Stem Cell Transplantation
• Mesenchymal Stem Cells (cytology, metabolism)
• Mice
• Mice, Inbred C57BL
• Pancreas (metabolism, pathology)
• Pancreatitis, Chronic (chemically induced, genetics, pathology, therapy)
• Tumor Necrosis Factor-alpha (antagonists & inhibitors, genetics, metabolism)