Undifferentiated Adipose Tissue Stem Cell Transplantation Promotes Hepatic Regeneration, Ameliorates Histopathologic Damage of the Liver, and Upregulates the Expression of Liver Regeneration- and Liver-Specific Genes in a Rat Model of Partial Hepatectomy

Objective. Adipose tissue stem cells (ADSCs) present a promising therapeutic method to alleviate liver failure (LF). The purpose of this prospective study was to evaluate the efficacy of undifferentiated ADSC transplantation on liver regeneration and on the expression of liver regeneration- and live...

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Main Authors: Konstantinos G. Apostolou, Ioannis G. Papanikolaou, Charalampos Katselis, Themistoklis Feretis, Dimitrios Kletsas, Manousos M. Konstadoulakis, Maria Lymperi, Angelica A. Saetta, Spiros Tsikalakis, George Agrogiannis, Efstratios Patsouris, George C. Zografos, Apostolos E. Papalois
Format: Article
Language:English
Published: Wiley 2018-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2018/1393607
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author Konstantinos G. Apostolou
Ioannis G. Papanikolaou
Charalampos Katselis
Themistoklis Feretis
Dimitrios Kletsas
Manousos M. Konstadoulakis
Maria Lymperi
Angelica A. Saetta
Spiros Tsikalakis
George Agrogiannis
Efstratios Patsouris
George C. Zografos
Apostolos E. Papalois
author_facet Konstantinos G. Apostolou
Ioannis G. Papanikolaou
Charalampos Katselis
Themistoklis Feretis
Dimitrios Kletsas
Manousos M. Konstadoulakis
Maria Lymperi
Angelica A. Saetta
Spiros Tsikalakis
George Agrogiannis
Efstratios Patsouris
George C. Zografos
Apostolos E. Papalois
author_sort Konstantinos G. Apostolou
collection DOAJ
description Objective. Adipose tissue stem cells (ADSCs) present a promising therapeutic method to alleviate liver failure (LF). The purpose of this prospective study was to evaluate the efficacy of undifferentiated ADSC transplantation on liver regeneration and on the expression of liver regeneration- and liver-specific genes, following 60% partial hepatectomy (PHx). Methods. Sixty female rats were subjected to PHx and were transplanted with 106 or 2 × 106 ADSCs, either into the portal vein (PV) or into the hepatic parenchyma. Animals of the control group were not transplanted and served as controls. Animals were sacrificed on the 4th, the 7th, or the 15th postoperative day (POD). Results. The transplanted ADSCs were successfully engrafted into the liver parenchyma and ameliorated the histopathologic damage on the 7th and 15th POD. All transplanted animals demonstrated a significantly higher liver regeneration rate on the 4th and 7th POD, compared with the control group. The expression of hepatocyte growth factor, α-fetoprotein, tyrosine aminotransferase, hepatocyte nuclear factor 4a, and cytochrome P450 1A2 was significantly upregulated, compared with the control group. Conclusions. Although undifferentiated, ADSC transplantation significantly enhanced the liver regeneration process. These findings may be proven clinically valuable, especially in cases of acute LF.
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spelling doaj-art-ac0d6307649440569f94696d421a8b8c2025-02-03T01:22:17ZengWileyStem Cells International1687-966X1687-96782018-01-01201810.1155/2018/13936071393607Undifferentiated Adipose Tissue Stem Cell Transplantation Promotes Hepatic Regeneration, Ameliorates Histopathologic Damage of the Liver, and Upregulates the Expression of Liver Regeneration- and Liver-Specific Genes in a Rat Model of Partial HepatectomyKonstantinos G. Apostolou0Ioannis G. Papanikolaou1Charalampos Katselis2Themistoklis Feretis3Dimitrios Kletsas4Manousos M. Konstadoulakis5Maria Lymperi6Angelica A. Saetta7Spiros Tsikalakis8George Agrogiannis9Efstratios Patsouris10George C. Zografos11Apostolos E. Papalois121st Department of Propaedeutic Surgery, University of Athens, School of Medicine, “Hippocration” Hospital, V. Sofias Avenue 114, 11527 Athens, Greece1st Department of Propaedeutic Surgery, University of Athens, School of Medicine, “Hippocration” Hospital, V. Sofias Avenue 114, 11527 Athens, Greece1st Department of Propaedeutic Surgery, University of Athens, School of Medicine, “Hippocration” Hospital, V. Sofias Avenue 114, 11527 Athens, Greece1st Department of Propaedeutic Surgery, University of Athens, School of Medicine, “Hippocration” Hospital, V. Sofias Avenue 114, 11527 Athens, GreeceLaboratory of Cell Proliferation & Ageing, National Center for Scientific Research “Demokritos”, Neapoleos 27 Street, 15341 Athens, Greece1st Department of Propaedeutic Surgery, University of Athens, School of Medicine, “Hippocration” Hospital, V. Sofias Avenue 114, 11527 Athens, Greece1st Department of Propaedeutic Surgery, University of Athens, School of Medicine, “Hippocration” Hospital, V. Sofias Avenue 114, 11527 Athens, Greece1st Department of Pathology, School of Medicine, University of Athens, Tetrapoleos 18, 11527 Athens, Greece1st Department of Pathology, School of Medicine, University of Athens, Tetrapoleos 18, 11527 Athens, Greece1st Department of Pathology, School of Medicine, University of Athens, Tetrapoleos 18, 11527 Athens, Greece1st Department of Pathology, School of Medicine, University of Athens, Tetrapoleos 18, 11527 Athens, Greece1st Department of Propaedeutic Surgery, University of Athens, School of Medicine, “Hippocration” Hospital, V. Sofias Avenue 114, 11527 Athens, GreeceExperimental Research Center, ELPEN, Marathonos Avenue 95, 19009 Athens, GreeceObjective. Adipose tissue stem cells (ADSCs) present a promising therapeutic method to alleviate liver failure (LF). The purpose of this prospective study was to evaluate the efficacy of undifferentiated ADSC transplantation on liver regeneration and on the expression of liver regeneration- and liver-specific genes, following 60% partial hepatectomy (PHx). Methods. Sixty female rats were subjected to PHx and were transplanted with 106 or 2 × 106 ADSCs, either into the portal vein (PV) or into the hepatic parenchyma. Animals of the control group were not transplanted and served as controls. Animals were sacrificed on the 4th, the 7th, or the 15th postoperative day (POD). Results. The transplanted ADSCs were successfully engrafted into the liver parenchyma and ameliorated the histopathologic damage on the 7th and 15th POD. All transplanted animals demonstrated a significantly higher liver regeneration rate on the 4th and 7th POD, compared with the control group. The expression of hepatocyte growth factor, α-fetoprotein, tyrosine aminotransferase, hepatocyte nuclear factor 4a, and cytochrome P450 1A2 was significantly upregulated, compared with the control group. Conclusions. Although undifferentiated, ADSC transplantation significantly enhanced the liver regeneration process. These findings may be proven clinically valuable, especially in cases of acute LF.http://dx.doi.org/10.1155/2018/1393607
spellingShingle Konstantinos G. Apostolou
Ioannis G. Papanikolaou
Charalampos Katselis
Themistoklis Feretis
Dimitrios Kletsas
Manousos M. Konstadoulakis
Maria Lymperi
Angelica A. Saetta
Spiros Tsikalakis
George Agrogiannis
Efstratios Patsouris
George C. Zografos
Apostolos E. Papalois
Undifferentiated Adipose Tissue Stem Cell Transplantation Promotes Hepatic Regeneration, Ameliorates Histopathologic Damage of the Liver, and Upregulates the Expression of Liver Regeneration- and Liver-Specific Genes in a Rat Model of Partial Hepatectomy
Stem Cells International
title Undifferentiated Adipose Tissue Stem Cell Transplantation Promotes Hepatic Regeneration, Ameliorates Histopathologic Damage of the Liver, and Upregulates the Expression of Liver Regeneration- and Liver-Specific Genes in a Rat Model of Partial Hepatectomy
title_full Undifferentiated Adipose Tissue Stem Cell Transplantation Promotes Hepatic Regeneration, Ameliorates Histopathologic Damage of the Liver, and Upregulates the Expression of Liver Regeneration- and Liver-Specific Genes in a Rat Model of Partial Hepatectomy
title_fullStr Undifferentiated Adipose Tissue Stem Cell Transplantation Promotes Hepatic Regeneration, Ameliorates Histopathologic Damage of the Liver, and Upregulates the Expression of Liver Regeneration- and Liver-Specific Genes in a Rat Model of Partial Hepatectomy
title_full_unstemmed Undifferentiated Adipose Tissue Stem Cell Transplantation Promotes Hepatic Regeneration, Ameliorates Histopathologic Damage of the Liver, and Upregulates the Expression of Liver Regeneration- and Liver-Specific Genes in a Rat Model of Partial Hepatectomy
title_short Undifferentiated Adipose Tissue Stem Cell Transplantation Promotes Hepatic Regeneration, Ameliorates Histopathologic Damage of the Liver, and Upregulates the Expression of Liver Regeneration- and Liver-Specific Genes in a Rat Model of Partial Hepatectomy
title_sort undifferentiated adipose tissue stem cell transplantation promotes hepatic regeneration ameliorates histopathologic damage of the liver and upregulates the expression of liver regeneration and liver specific genes in a rat model of partial hepatectomy
url http://dx.doi.org/10.1155/2018/1393607
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