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Cited by 82Mesenchymal stem cell researchLiver physiology and pathologyTissue Engineering and Regenerative Medicine

Lipopolysaccharide preconditioning of adipose-derived stem cells improves liver-regenerating activity of the secretome

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Lee, Sang Chul, Jeong, Hye Jin, Lee, Sang Kuon, Kim, Say-June·2015·Stem Cell Research & Therapy
DOI 10.1186/s13287-015-0072-7PMC PMC4416308
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Abstract

Introduction: Growing recognition of paracrine mechanisms in stem cell plasticity has resulted in considerable interest in stem cell-derived secretome. The aim of this study was to investigate the effects of lipopolysaccharide (LPS) preconditioning on the composition and hepatic regenerative activity of adipose-derived stem cell (ASC) secretome. Methods: Conditioned medium (CM) and LPS-CM were obtained after culturing human ASCs without or with low-dose LPS (0.5 ng/mL) for 24 hours. Untreated and thioacetamide-treated mouse AML12 hepatocytes were incubated for 24 hours with the control medium, LPS (0.5 ng/mL), CM, and LPS-CM and then cell viabilities were compared. CM and LPS-CM were also intravenously administered to partially hepatectomized mice, and their effects on liver regeneration were assessed by using liver weight measurements, immunohistochemistry, and Western blotting. Results: In the in vitro experiments, LPS preconditioning of ASCs enhanced the mRNA expression levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), hepatocyte growth factor, and vascular endothelial growth factor, which evoke inflammatory response or liver regeneration. LPS-CM significantly promoted thioacetamide-damaged AML12 cell viability compared with CM-incubated cells and the control cells (77%, 69%, and 65% P <0.05). In the in vivo experiment, LPS-CM infusion into the partially hepatectomized mice significantly reduced serum IL-6 and TNF-α levels compared with the other groups ( P <0.05) on days 1 and 2 after partial hepatectomy. Moreover, LPS-CM infusion enhanced liver regeneration (based on the liver weight changes at day 7 after partial hepatectomy, 3.73% versus 3.22% in the CM group; P <0.05) and significantly reduced the elevated serum levels of aspartate transaminase and alanine transaminase (at day 1, P <0.05). Conclusions: Our results suggest that LPS preconditioning effectively stimulates ASCs to produce the secretome beneficial to hepatic regeneration. Thus, optimizing ASC secretome profile by LPS preconditioning could be a promising approach to treat liver diseases by using stem cells.

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  • LPS-preconditioning-MSC-derived secretome has better liver regeneration and anti-inflammatory properties compared to non-primed MSC-secretome.

    “This result indicates that LPS-preconditioning-MSC-derived secretome has better liver regeneration and anti-inflammatory properties compared to non-primed MSC-secretome [144].”

    From Mesenchymal stem cell secretome for regenerative medicine: Where do we stand? (2025) · cites this paper as [144]

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References 65 · Cited by 82

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Authors
Lee, S. C., Jeong, H. J., Lee, S. K., & Kim, S.-J.
Affiliations
The Catholic University of Korea Daejeon St. Mary's Hospital (KR)
Corresponding author
Kim, Say-June
ORCID
Venue
Stem Cell Research & Therapy
Publisher
Springer Science and Business Media LLC
Published
2015-04-14
Volume
6
Issue
1
Pages
75-75
ISSN
1757-6512 (ISSN-L)
DOI
10.1186/s13287-015-0072-7
PMC
PMC4416308
OpenAlex
W2146134260
Cited by
82
References
65
Citations by year
2026: 4 · 2025: 3 · 2024: 9 · 2023: 9 · 2022: 11 · 2021: 14 · 2020: 7 · 2019: 13 · 2018: 3 · 2017: 4 · 2016: 4 · 2015: 1
FWCI
2.24
Type
journal article
Language
en
Open access
Licence
Locations
  • Stem Cell Research & Therapy (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • Korea University
  • Catholic University of Korea
Topics
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
Keywords
lipopolysaccharide preconditioning, adipose-derived stem cells, stem cell secretome, conditioned medium, liver regeneration, partial hepatectomy, hepatocyte viability, thioacetamide-induced hepatotoxicity, interleukin-6, TNF-α, hepatocyte growth factor, vascular endothelial growth factor, paracrine signaling, liver disease treatment
MeSH terms
Adipose Tissue, Animals, Cell Line, Cell Survival, Humans, Inflammation, Lipopolysaccharides, Liver, Liver Regeneration, Male, Mice, Inbred BALB C, RNA, Messenger, Stem Cells, Thioacetamide, Signal Transduction, Case-Control Studies, Cytokines, Culture Media, Conditioned, Paracrine Communication, Cell Proliferation, Mice

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