Autologous bone marrow-derived cell transplantation in decompensated alcoholic liver disease: what is the impact on liver histology and gene expression patterns?
Abstract 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 a...
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doaj-715514d95b984dfe84c257ae5038b80d2020-11-24T20:55:15ZengBMCStem Cell Research & Therapy1757-65122017-04-018111010.1186/s13287-017-0541-2Autologous bone marrow-derived cell transplantation in decompensated alcoholic liver disease: what is the impact on liver histology and gene expression patterns?Nicolas Lanthier0Nathalie Lin-Marq1Laura Rubbia-Brandt2Sophie Clément3Nicolas Goossens4Laurent Spahr5Gastroenterology and Hepatology, University Hospitals and Faculty of MedicineClinical Pathology, University Hospitals and Faculty of MedicineClinical Pathology, University Hospitals and Faculty of MedicineClinical Pathology, University Hospitals and Faculty of MedicineGastroenterology and Hepatology, University Hospitals and Faculty of MedicineGastroenterology and Hepatology, University Hospitals and Faculty of MedicineAbstract 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.http://link.springer.com/article/10.1186/s13287-017-0541-2Stem cell transplantationMacrophageKupffer cellSPINK1CD68HGF |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Nicolas Lanthier Nathalie Lin-Marq Laura Rubbia-Brandt Sophie Clément Nicolas Goossens Laurent Spahr |
spellingShingle |
Nicolas Lanthier Nathalie Lin-Marq Laura Rubbia-Brandt Sophie Clément Nicolas Goossens Laurent Spahr Autologous bone marrow-derived cell transplantation in decompensated alcoholic liver disease: what is the impact on liver histology and gene expression patterns? Stem Cell Research & Therapy Stem cell transplantation Macrophage Kupffer cell SPINK1 CD68 HGF |
author_facet |
Nicolas Lanthier Nathalie Lin-Marq Laura Rubbia-Brandt Sophie Clément Nicolas Goossens Laurent Spahr |
author_sort |
Nicolas Lanthier |
title |
Autologous bone marrow-derived cell transplantation in decompensated alcoholic liver disease: what is the impact on liver histology and gene expression patterns? |
title_short |
Autologous bone marrow-derived cell transplantation in decompensated alcoholic liver disease: what is the impact on liver histology and gene expression patterns? |
title_full |
Autologous bone marrow-derived cell transplantation in decompensated alcoholic liver disease: what is the impact on liver histology and gene expression patterns? |
title_fullStr |
Autologous bone marrow-derived cell transplantation in decompensated alcoholic liver disease: what is the impact on liver histology and gene expression patterns? |
title_full_unstemmed |
Autologous bone marrow-derived cell transplantation in decompensated alcoholic liver disease: what is the impact on liver histology and gene expression patterns? |
title_sort |
autologous bone marrow-derived cell transplantation in decompensated alcoholic liver disease: what is the impact on liver histology and gene expression patterns? |
publisher |
BMC |
series |
Stem Cell Research & Therapy |
issn |
1757-6512 |
publishDate |
2017-04-01 |
description |
Abstract 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. |
topic |
Stem cell transplantation Macrophage Kupffer cell SPINK1 CD68 HGF |
url |
http://link.springer.com/article/10.1186/s13287-017-0541-2 |
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