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Autologous bone marrow-derived cell transplantation in decompensated alcoholic liver disease: what is the impact on liver histology and gene expression patterns?

Abstract Liver stem cell therapy (SCT) has been suggested as a promising means to improve liver regeneration in advanced liver disease. However, data from trials are heterogeneous, with no systematic histological evaluation. The aim of this study is to specifically analyze the effect of autologous SCT on liver regeneration and on gene expression changes.
PMID
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Authors

Mayor MeshTerms
Keywords

Alcoholic hepatitis

CD68

Cirrhosis

HGF

Kupffer cell

Macrophage

SPINK1

Stem cell transplantation

Journal Title stem cell research & therapy
Publication Year Start




PMID- 28420441
OWN - NLM
STAT- In-Process
DA  - 20170419
LR  - 20170421
IS  - 1757-6512 (Electronic)
IS  - 1757-6512 (Linking)
VI  - 8
IP  - 1
DP  - 2017 Apr 18
TI  - Autologous bone marrow-derived cell transplantation in decompensated alcoholic
      liver disease: what is the impact on liver histology and gene expression
      patterns?
PG  - 88
LID - 10.1186/s13287-017-0541-2 [doi]
AB  - BACKGROUND: Liver stem cell therapy (SCT) has been suggested as a promising means
      to improve liver regeneration in advanced liver disease. However, data from
      trials are heterogeneous, with no systematic histological evaluation. The aim of 
      this study is to specifically analyze the effect of autologous SCT on liver
      regeneration and on gene expression changes. METHODS: Individuals in the
      randomized controlled trial of SCT in alcoholic hepatitis with paired liver
      biopsies were included (n = 58). Immunohistochemistry (Ki67, K7, and CD68), in
      situ hybridization (SPINK1), and global gene expression analysis were performed
      on liver biopsies (30 control patients and 28 patients with transarterial
      administration of bone marrow-derived stem cells) both at baseline and after 4
      weeks of follow-up. RESULTS: No difference between the two groups could be
      observed regarding the proliferative hepatocyte number, proliferative K7-positive
      cells, or total K7-positive cells at the 4-week follow-up liver biopsy. However, 
      patients who received SCT showed a more important liver macrophagic expansion as 
      compared to standard treatment. Transcriptome data revealed changes in genes
      linked with inflammation (CD68 and SAA), regeneration (SPINK1 and HGF), fibrosis 
      (COL1A1), and stem cells (CD45). No changes in gene pathways involved in liver
      growth and cell cycle proteins were evident. SPINK1 mRNA was present by in situ
      hybridization at week 4 in SCT patients in the liver parenchyma areas adjacent to
      macrophage recruitment and liver cell proliferation. CONCLUSIONS: The analysis of
      liver tissue after SCT demonstrated an expansion of macrophages concurrent with
      an upregulated expression of genes involved in inflammatory and regenerative
      pathways. With the negative results from the clinical trial, the impact of the
      SCT has to be interpreted as weak, and it is not able to modify the clinical
      course of this severe liver disease.
FAU - Lanthier, Nicolas
AU  - Lanthier N
AD  - Gastroenterology and Hepatology, University Hospitals and Faculty of Medicine, 4,
      Rue Gabrielle Perret-Gentil CH-1211, Geneva 14, Switzerland.
AD  - Laboratory of Gastroenterology and Hepatology, Institut de Recherche
      Experimentale et Clinique, Universite catholique de Louvain, Brussels, Belgium.
FAU - Lin-Marq, Nathalie
AU  - Lin-Marq N
AD  - Clinical Pathology, University Hospitals and Faculty of Medicine, Geneva,
      Switzerland.
FAU - Rubbia-Brandt, Laura
AU  - Rubbia-Brandt L
AD  - Clinical Pathology, University Hospitals and Faculty of Medicine, Geneva,
      Switzerland.
FAU - Clement, Sophie
AU  - Clement S
AD  - Clinical Pathology, University Hospitals and Faculty of Medicine, Geneva,
      Switzerland.
FAU - Goossens, Nicolas
AU  - Goossens N
AD  - Gastroenterology and Hepatology, University Hospitals and Faculty of Medicine, 4,
      Rue Gabrielle Perret-Gentil CH-1211, Geneva 14, Switzerland.
FAU - Spahr, Laurent
AU  - Spahr L
AD  - Gastroenterology and Hepatology, University Hospitals and Faculty of Medicine, 4,
      Rue Gabrielle Perret-Gentil CH-1211, Geneva 14, Switzerland.
      [email protected]
LA  - eng
PT  - Journal Article
DEP - 20170418
PL  - England
TA  - Stem Cell Res Ther
JT  - Stem cell research & therapy
JID - 101527581
PMC - PMC5395856
OTO - NOTNLM
OT  - Alcoholic hepatitis
OT  - CD68
OT  - Cirrhosis
OT  - HGF
OT  - Kupffer cell
OT  - Macrophage
OT  - SPINK1
OT  - Stem cell transplantation
EDAT- 2017/04/20 06:00
MHDA- 2017/04/20 06:00
CRDT- 2017/04/20 06:00
PHST- 2016/12/22 [received]
PHST- 2017/03/22 [accepted]
PHST- 2017/03/20 [revised]
AID - 10.1186/s13287-017-0541-2 [doi]
AID - 10.1186/s13287-017-0541-2 [pii]
PST - epublish
SO  - Stem Cell Res Ther. 2017 Apr 18;8(1):88. doi: 10.1186/s13287-017-0541-2.

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