Nerve growth factor-mediated paracrine regulation of hepatic stellate cells by multipotent mesenchymal stromal cells

Lin, Nan; Hu, Kunpeng; Chen, Si; Xie, Shujie; Tang, Zhaofeng; Lin, Jizong; Xu, Ruiyun

doi:10.1016/j.lfs.2009.06.007

Cited by 61Mesenchymal stem cell researchLiver physiology and pathologyLiver Disease and Transplantation

Nerve growth factor-mediated paracrine regulation of hepatic stellate cells by multipotent mesenchymal stromal cells

Lin, Nan, Hu, Kunpeng, Chen, Si, Xie, Shujie, Tang, Zhaofeng, Lin, Jizong, Xu, Ruiyun·2009·Life Sciences

DOI 10.1016/j.lfs.2009.06.007

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Abstract

Aims Multipotent mesenchymal stromal cells (MSC) have been reported to prevent the development of liver fibrosis and have emerged as a promising strategy for cell-based therapy. However, the underlying therapeutic mechanism remains unclear. Hepatic stellate cells (SC) activation is a pivotal event in the development of liver fibrosis. Main methods We hypothesized that MSC play an important role in regulating SC proliferation and apoptosis through paracrine mechanisms. To investigate the paracrine interactions between MSC and SC, a co-culture experimental model was developed using human MSC (hMSC) and human SC (hSC). Key findings We demonstrate that hMSC and hSC both express nerve growth factor (NGF) receptor p75. Results acquired from transwell co-culture experiments using hSC and hMSC showed that hMSC secrete NGF, which enhances hSC apoptosis. Transcription factor nuclear factor kappa B (NF-KappaB) and B cell leukemia-xl (Bcl-xl) take part in the process. Significance These findings demonstrated that hMSC indirectly modulate activated hSC in vitro via NGF-mediated signaling cascades and provide a potential mechanism of how transplanted MSC are effective in treating liver fibrosis.

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BM-hMSC-derived NGF enhances hHSC apoptosis by inhibiting NF-κB and the expression of the anti-apoptotic gene Bcl-xl.
“BM-hMSC-derived NGF was also reported to enhance hHSC apoptosis by inhibiting nuclear factor kappa B (NF-κB) and the expression of the anti-apoptotic gene Bcl-xl [188].”
From Mechanisms, efficacy, and future perspectives of cellular-based therapies for liver fibrosis/cirrhosis: focusing on mesenchymal stromal cells (2025) · cites this paper as [188]

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Authors: Lin, N., Hu, K., Chen, S., Xie, S., Tang, Z., Lin, J., & Xu, R.
Affiliations: Sun Yat-sen University (CN)
Corresponding author: Xu, Ruiyun
ORCID: Lin, Nan
Hu, Kunpeng
Chen, Si
Xie, Shujie
Venue: Life Sciences
Publisher: Elsevier BV
Published: 2009-08
Volume: 85
Issue: 7-8
Pages: 291-295
ISSN: 0024-3205 (ISSN-L)
DOI: 10.1016/j.lfs.2009.06.007
OpenAlex: W1986753454
Cited by: 61
References: 27
Citations by year: 2026: 2 · 2025: 5 · 2024: 1 · 2023: 4 · 2022: 3 · 2021: 7 · 2020: 3 · 2019: 3 · 2018: 4 · 2017: 5 · 2016: 1 · 2015: 12 · 2014: 4 · 2013: 3 · 2012: 2
FWCI: 0.63
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Life Sciences (publishedVersion)
PubMed (publishedVersion)
Funders: Sun Yat-sen University
Topics: Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
Health Sciences › Medicine › Hepatology › Liver physiology and pathology
Health Sciences › Medicine › Hepatology › Liver Disease and Transplantation
Keywords: nerve growth factor, hepatic stellate cells, mesenchymal stem cells, liver fibrosis, paracrine signaling, p75 NGF receptor, stellate cell apoptosis, NF-κB, Bcl-xL, co-culture, cell therapy
MeSH terms: Cells, Cultured, Culture Media, Genetic Vectors, Humans, Recombinant Proteins, Transfection, Apoptosis, Coculture Techniques, Paracrine Communication, Reverse Transcriptase Polymerase Chain Reaction, Receptor, Nerve Growth Factor, Nerve Growth Factor, Multipotent Stem Cells, Cell Proliferation, Hepatic Stellate Cells, Mesenchymal Stem Cells

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Nerve growth factor-mediated paracrine regulation of hepatic stellate cells by multipotent mesenchymal stromal cells

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