Autologous bone marrow-derived cell transplantation in decompensated alcoholic liver disease: what is the impact on liver histology and gene expression patterns?
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| Title: | Autologous bone marrow-derived cell transplantation in decompensated alcoholic liver disease: what is the impact on liver histology and gene expression patterns? |
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| Authors: | Lanthier, Nicolas, Lin-Marq, Nathalie, Rubbia-Brandt, Laura, Clément, Sophie, Goossens, Nicolas, Spahr, Laurent |
| Contributors: | UCL - SSS/IREC/GAEN - Pôle d'Hépato-gastro-entérologie, UCL - (SLuc) Service de gastro-entérologie |
| Source: | Stem Cell Res Ther Stem Cell Research & Therapy, Vol 8, Iss 1, Pp 1-10 (2017) Stem Cell Research & Therapy, Vol. 8, No 1 (2017) P. 88 Stem Cell Research & Therapy, Vol. 8, no. 1, p. 88 [1-10] (2017) |
| Publisher Information: | Springer Science and Business Media LLC, 2017. |
| Publication Year: | 2017 |
| Subject Terms: | Male, 0301 basic medicine, Medicine (General), Macrophage, Transplantation, Autologous/adverse effects, ddc:616.07, Biochemistry, SPINK1, Mesenchymal Stem Cell Transplantation/adverse effects, HGF, Antigens, CD/genetics/metabolism, ddc:616, 0303 health sciences, Hepatocyte Growth Factor, Stem cell transplantation, Middle Aged, Antigens, CD45/genetics/metabolism, 3. Good health, Cirrhosis, Collagen Type I/genetics/metabolism, Mesenchymal Stromal Cells/cytology/metabolism, Liver, Carrier Proteins/genetics/metabolism, Female, Alcoholic hepatitis, Hepatocyte Growth Factor/genetics/metabolism, Adult, Kupffer cell, Antigens, Differentiation, Myelomonocytic, QD415-436, 616.07, Mesenchymal Stem Cell Transplantation, Collagen Type I, Serum Amyloid A Protein/genetics/metabolism, 03 medical and health sciences, R5-920, Antigens, CD, Macrophages/metabolism, Humans, CD68, Liver Diseases, Alcoholic, Aged, Serum Amyloid A Protein, Liver/metabolism/pathology, Liver Diseases, Alcoholic/therapy, Research, Macrophages, Mesenchymal Stem Cells, Collagen Type I, alpha 1 Chain, Leukocyte Common Antigens, Antigens, Differentiation, Myelomonocytic/genetics/metabolism, Carrier Proteins, Transcriptome |
| Description: | 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.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.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.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. |
| Document Type: | Article Other literature type |
| File Description: | application/pdf |
| Language: | English |
| ISSN: | 1757-6512 |
| DOI: | 10.1186/s13287-017-0541-2 |
| Access URL: | https://stemcellres.biomedcentral.com/track/pdf/10.1186/s13287-017-0541-2 https://pubmed.ncbi.nlm.nih.gov/28420441 https://doaj.org/article/715514d95b984dfe84c257ae5038b80d https://pubmed.ncbi.nlm.nih.gov/28420441/ https://link.springer.com/article/10.1186/s13287-017-0541-2 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5395856 https://archive-ouverte.unige.ch/unige:94214 https://paperity.org/p/79476832/autologous-bone-marrow-derived-cell-transplantation-in-decompensated-alcoholic-liver https://archive-ouverte.unige.ch/unige:94214/ATTACHMENT01 https://archive-ouverte.unige.ch/unige:94214 https://archive-ouverte.unige.ch/unige:94214 https://doi.org/10.1186/s13287-017-0541-2 https://hdl.handle.net/2078.1/185761 |
| Rights: | CC BY |
| Accession Number: | edsair.doi.dedup.....d4e18b6cfa6d41171d3cd99da0eff4db |
| Database: | OpenAIRE |
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Nájsť tento článok vo Web of Science | 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.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.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.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. |
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| ISSN: | 17576512 |
| DOI: | 10.1186/s13287-017-0541-2 |