Cited by 31Liver physiology and pathologyMesenchymal stem cell researchTissue Engineering and Regenerative Medicine

Repair of liver mediated by adult mouse liver neuro-glia antigen 2-positive progenitor cell transplantation in a mouse model of cirrhosis

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Zhang, Hongyu, Siegel, Christopher T., Shuai, Ling, Lai, Jiejuan, Zeng, Linli, Zhang, Yujun, Lai, Xiangdong, Bie, Ping +1 more·2016·Scientific Reports

Abstract

NG2-expressing cells are a population of periportal vascular stem/progenitors (MLpvNG2 + cells) that were isolated from healthy adult mouse liver by using a “Percoll-Plate-Wait” procedure. We demonstrated that isolated cells are able to restore liver function after transplantation into a cirrhotic liver and co-localized with the pericyte marker (immunohistochemistry: PDGFR-β) and CK19. Cells were positive for: stem cell (Sca-1, CD133, Dlk) and liver stem cell markers (EpCAM, CD14, CD24, CD49f); and negative for: hematopoietic (CD34, CD45) and endothelial markers (CD31, vWf, von Willebrand factor). Cells were transplanted (1 × 10 6 cells) in mice with diethylnitrosamine-induced cirrhosis at week 6. Cells showed increased hepatic associated gene expression of alpha-fetoprotein (AFP), Albumin (Alb), Glucose-6-phosphatase (G6Pc), SRY (sex determining region Y)-box 9 (Sox9), hepatic nuclear factors (HNF1a, HNF1β, HNF3β, HNF4α, HNF6, Epithelial cell adhesion molecule (EpCAM), Leucine-rich repeated-containing G-protein coupled receptor 5-positive (Lgr5) and Tyrosine aminotransferase (TAT). Cells showed decreased fibrogenesis, hepatic stellate cell infiltration, Kupffer cells and inflammatory cytokines. Liver function markers improved. In a cirrhotic liver environment, cells could differentiate into hepatic lineages. In addition, grafted MLpvNG2 + cells could mobilize endogenous stem/progenitors to participate in liver repair. These results suggest that MLpvNG2 + cells may be novel adult liver progenitors that participate in liver regeneration.

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  • PPWP has been stably used for the isolation of NG2+ cells from multiple adult tissues.

    “which has been stably used for the isolation of NG2+ cells from multiple adult tissues [21, 23]”

    From New advances of NG2-expressing cell subset in marrow mesenchymal stem cells as novel therapeutic tools for liver fibrosis/cirrhosis (2024) · cites this paper as [23]

    The Methods section (page not supplied) describes using the Percoll-Plate-Wait procedure to isolate NG2+ cells from adult mouse liver. The Results report that the isolated cells retained similar characteristics through eight passages. Our copy does not establish that the procedure has been used to isolate NG2+ cells from multiple adult tissues. (LLM, conf=0.87)

    Experimental — accuracy not yet measured
  • Most passaged m-NG2/BMMSCs exhibited a diamond-shaped flaky morphology similar to cells isolated from multiple other organs but clearly different from spindle-shaped m-BMMSCs.

    “most passaged (P) cells exhibited a diamond-shaped flaky morphology (Fig. 1Aa; Suppl. Fig. S1Bd, pink cartoon marks assumed NG2+ cells), similar to the cells isolated from multiple other organs [21, 23], but those morphologies were clearly different from those of spindle-shaped m-BMMSCs”

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Authors
Zhang, H., Siegel, C. T., Shuai, L., Lai, J., Zeng, L., Zhang, Y., Lai, X., Bie, P., & Bai, L.
Affiliations
Case Western Reserve University (US)
Corresponding author
  • Bie, Ping
  • Bai, Lianhua
Venue
Scientific Reports
Published
2016-02-24
Volume
6
Issue
1
Pages
21783-21783
ISSN
2045-2322 (ISSN-L)
OpenAlex
W2418471211
Cited by
30
References
84
Citations by year
2026: 2 · 2025: 3 · 2024: 5 · 2023: 4 · 2022: 5 · 2021: 3 · 2020: 3 · 2019: 1 · 2018: 1 · 2017: 1 · 2016: 2
FWCI
1.21
Type
journal article
Language
en
Open access
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • National Natural Science Foundation of China
  • Southwest Hospital
Topics
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
  • Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
Keywords
liver cirrhosis, liver regeneration, liver progenitor cells, cell transplantation, liver fibrosis, liver repair
MeSH terms
Chondroitin Sulfate Proteoglycan 4, Animals, Antigens, Cell Differentiation, Cell Movement, Cells, Cultured, Kupffer Cells, Liver, Liver Cirrhosis, Liver Regeneration, Male, Mice, Inbred C57BL, Proteoglycans, Stem Cell Transplantation, Hepatic Stellate Cells

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