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Adipose Stem Cell Therapy Mitigates Chronic Pancreatitis via Differentiation into Acinar-like Cells in Mice.
Mol Ther. 2017 11 01; 25(11):2490-2501.MT

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+Show Affiliations

Department of Surgery, Medical University of South Carolina, Charleston, SC 29425, USA; Qingdao Agricultural University, Qingdao, Shandong 266109, China.Department of Surgery, Medical University of South Carolina, Charleston, SC 29425, USA.Department of Surgery, Medical University of South Carolina, Charleston, SC 29425, USA.Qingdao Agricultural University, Qingdao, Shandong 266109, China.Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, USA.Bioengineering Department, Clemson University, Clemson, SC 29634, USA.Department of Surgery, Medical University of South Carolina, Charleston, SC 29425, USA.Department of Surgery, Medical University of South Carolina, Charleston, SC 29425, USA. Electronic address: wangho@musc.edu.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28784560

Citation

Sun, Zhen, et al. "Adipose Stem Cell Therapy Mitigates Chronic Pancreatitis Via Differentiation Into Acinar-like Cells in Mice." Molecular Therapy : the Journal of the American Society of Gene Therapy, vol. 25, no. 11, 2017, pp. 2490-2501.
Sun Z, Gou W, Kim DS, et al. Adipose Stem Cell Therapy Mitigates Chronic Pancreatitis via Differentiation into Acinar-like Cells in Mice. Mol Ther. 2017;25(11):2490-2501.
Sun, Z., Gou, W., Kim, D. S., Dong, X., Strange, C., Tan, Y., Adams, D. B., & Wang, H. (2017). Adipose Stem Cell Therapy Mitigates Chronic Pancreatitis via Differentiation into Acinar-like Cells in Mice. Molecular Therapy : the Journal of the American Society of Gene Therapy, 25(11), 2490-2501. https://doi.org/10.1016/j.ymthe.2017.06.016
Sun Z, et al. Adipose Stem Cell Therapy Mitigates Chronic Pancreatitis Via Differentiation Into Acinar-like Cells in Mice. Mol Ther. 2017 11 1;25(11):2490-2501. PubMed PMID: 28784560.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Adipose Stem Cell Therapy Mitigates Chronic Pancreatitis via Differentiation into Acinar-like Cells in Mice. AU - Sun,Zhen, AU - Gou,Wenyu, AU - Kim,Do-Sung, AU - Dong,Xiao, AU - Strange,Charlie, AU - Tan,Yu, AU - Adams,David B, AU - Wang,Hongjun, Y1 - 2017/08/04/ PY - 2016/11/25/received PY - 2017/06/10/revised PY - 2017/06/17/accepted PY - 2017/8/9/pubmed PY - 2018/6/15/medline PY - 2017/8/9/entrez KW - acinar cells KW - adipose stem cell therapy KW - differentiation KW - ethanol and cerulean-induced chronic pancreatitis mouse model KW - fibrosis KW - inflammation KW - mesenchymal stem cells SP - 2490 EP - 2501 JF - Molecular therapy : the journal of the American Society of Gene Therapy JO - Mol. Ther. VL - 25 IS - 11 N2 - 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. SN - 1525-0024 UR - https://www.unboundmedicine.com/medline/citation/28784560/Adipose_Stem_Cell_Therapy_Mitigates_Chronic_Pancreatitis_via_Differentiation_into_Acinar_like_Cells_in_Mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1525-0016(17)30279-4 DB - PRIME DP - Unbound Medicine ER -