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Adipose-derived mesenchymal stem cells promote liver regeneration and suppress rejection in small-for-size liver allograft

Adipose-derived mesenchymal stem cells (ADSCs) possess a liver regeneration capacity and immunosuppressive activity and hold promise in autologous cell-based technology. This study aimed to determine whether autologous ADSCs can improve outcomes in the rat reduced size liver transplantation model. A... Full description

Journal Title: Transplant immunology 2017-12, Vol.45, p.1-7
Main Author: Gao, Wei
Other Authors: Zhang, Luzhou , Zhang, Yanyan , Sun, Chao , Chen, Xiaobo , Wang, Yuliang
Format: Electronic Article Electronic Article
Language: English
Subjects:
Publisher: Netherlands: Elsevier B.V
ID: ISSN: 0966-3274
Link: https://www.ncbi.nlm.nih.gov/pubmed/28778713
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recordid: cdi_proquest_miscellaneous_1926687434
title: Adipose-derived mesenchymal stem cells promote liver regeneration and suppress rejection in small-for-size liver allograft
format: Article
creator:
  • Gao, Wei
  • Zhang, Luzhou
  • Zhang, Yanyan
  • Sun, Chao
  • Chen, Xiaobo
  • Wang, Yuliang
subjects:
  • Acute Disease
  • Acute rejection
  • Adipose Tissue - cytology
  • Adipose-derived mesenchymal stem cells
  • Analysis
  • Animals
  • Bilirubin
  • Cells, Cultured
  • Cytokines - metabolism
  • Enzymes
  • Graft Rejection - immunology
  • Graft Rejection - prevention & control
  • Histochemistry
  • Immune Tolerance
  • Interleukins
  • Liver
  • Liver - physiology
  • Liver Regeneration
  • Liver Transplantation
  • Male
  • Medical research
  • Medicine, Experimental
  • Mesenchymal Stem Cell Transplantation
  • Mesenchymal Stromal Cells - physiology
  • Organ Size
  • Phosphates
  • Rats
  • Rats, Inbred BN
  • Rats, Inbred Lew
  • Recovery of Function
  • Reduced size liver transplantation
  • Stem cells
  • T cells
  • T-Lymphocytes, Regulatory - immunology
  • Transforming growth factors
  • Transplantation
  • Transplantation, Homologous
ispartof: Transplant immunology, 2017-12, Vol.45, p.1-7
description: Adipose-derived mesenchymal stem cells (ADSCs) possess a liver regeneration capacity and immunosuppressive activity and hold promise in autologous cell-based technology. This study aimed to determine whether autologous ADSCs can improve outcomes in the rat reduced size liver transplantation model. Allogeneic 50% orthotopic liver transplantation followed by administration of autologous ADSCs delivered into the portal vein system was conducted in LEW donor rats and BN recipient rats with phosphate buffered solution (PBS) infusion used as the control. Liver grafts and recipient serum were obtained. We assessed histopathology, regeneration, apoptosis, serum liver enzymes, serum cytokines, and circulating regulatory T cells (Tregs) on postoperative day (POD) 7 and 14. It was found that ADSCs significantly reduced acute rejection and improved the allograft's survival times (median, 24days). Liver function, as assessed by the levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin, as well as liver apoptosis was significantly alleviated in the ADSC group compared with the control group. In addition, ADSC therapy markedly promoted the expression of PCNA in the allograft. Furthermore, levels of interleukin (IL)-10 and transforming growth factor (TGF)-β1 were significantly elevated, whereas those of IL-2 and IL-17 levels were significantly reduced in the ADSC group when compared to the control group. Moreover, flow cytometry analysis revealed that peripheral Tregs had been significantly increased by the infusion of ADSCs. These results demonstrate that implanted autologous ADSCs improve allogeneic reduced size liver allograft outcomes by attenuating acute rejection and reducing inflammatory responses, as well as enhancing liver regeneration. •ADSC improve allogeneic reduced size liver allograft survival.•ADSC therapy after 50% RSLT inhibits hepatocyte apoptosis, enhances hepatocyte regeneration, and attenuates acute rejection.•ADSC can exert their immunosuppressive effects is by inducing the production of Tregs.
language: eng
source:
identifier: ISSN: 0966-3274
fulltext: no_fulltext
issn:
  • 0966-3274
  • 1878-5492
url: Link


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titleAdipose-derived mesenchymal stem cells promote liver regeneration and suppress rejection in small-for-size liver allograft
creatorGao, Wei ; Zhang, Luzhou ; Zhang, Yanyan ; Sun, Chao ; Chen, Xiaobo ; Wang, Yuliang
creatorcontribGao, Wei ; Zhang, Luzhou ; Zhang, Yanyan ; Sun, Chao ; Chen, Xiaobo ; Wang, Yuliang
descriptionAdipose-derived mesenchymal stem cells (ADSCs) possess a liver regeneration capacity and immunosuppressive activity and hold promise in autologous cell-based technology. This study aimed to determine whether autologous ADSCs can improve outcomes in the rat reduced size liver transplantation model. Allogeneic 50% orthotopic liver transplantation followed by administration of autologous ADSCs delivered into the portal vein system was conducted in LEW donor rats and BN recipient rats with phosphate buffered solution (PBS) infusion used as the control. Liver grafts and recipient serum were obtained. We assessed histopathology, regeneration, apoptosis, serum liver enzymes, serum cytokines, and circulating regulatory T cells (Tregs) on postoperative day (POD) 7 and 14. It was found that ADSCs significantly reduced acute rejection and improved the allograft's survival times (median, 24days). Liver function, as assessed by the levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin, as well as liver apoptosis was significantly alleviated in the ADSC group compared with the control group. In addition, ADSC therapy markedly promoted the expression of PCNA in the allograft. Furthermore, levels of interleukin (IL)-10 and transforming growth factor (TGF)-β1 were significantly elevated, whereas those of IL-2 and IL-17 levels were significantly reduced in the ADSC group when compared to the control group. Moreover, flow cytometry analysis revealed that peripheral Tregs had been significantly increased by the infusion of ADSCs. These results demonstrate that implanted autologous ADSCs improve allogeneic reduced size liver allograft outcomes by attenuating acute rejection and reducing inflammatory responses, as well as enhancing liver regeneration. •ADSC improve allogeneic reduced size liver allograft survival.•ADSC therapy after 50% RSLT inhibits hepatocyte apoptosis, enhances hepatocyte regeneration, and attenuates acute rejection.•ADSC can exert their immunosuppressive effects is by inducing the production of Tregs.
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subjectAcute Disease ; Acute rejection ; Adipose Tissue - cytology ; Adipose-derived mesenchymal stem cells ; Analysis ; Animals ; Bilirubin ; Cells, Cultured ; Cytokines - metabolism ; Enzymes ; Graft Rejection - immunology ; Graft Rejection - prevention & control ; Histochemistry ; Immune Tolerance ; Interleukins ; Liver ; Liver - physiology ; Liver Regeneration ; Liver Transplantation ; Male ; Medical research ; Medicine, Experimental ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stromal Cells - physiology ; Organ Size ; Phosphates ; Rats ; Rats, Inbred BN ; Rats, Inbred Lew ; Recovery of Function ; Reduced size liver transplantation ; Stem cells ; T cells ; T-Lymphocytes, Regulatory - immunology ; Transforming growth factors ; Transplantation ; Transplantation, Homologous
ispartofTransplant immunology, 2017-12, Vol.45, p.1-7
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descriptionAdipose-derived mesenchymal stem cells (ADSCs) possess a liver regeneration capacity and immunosuppressive activity and hold promise in autologous cell-based technology. This study aimed to determine whether autologous ADSCs can improve outcomes in the rat reduced size liver transplantation model. Allogeneic 50% orthotopic liver transplantation followed by administration of autologous ADSCs delivered into the portal vein system was conducted in LEW donor rats and BN recipient rats with phosphate buffered solution (PBS) infusion used as the control. Liver grafts and recipient serum were obtained. We assessed histopathology, regeneration, apoptosis, serum liver enzymes, serum cytokines, and circulating regulatory T cells (Tregs) on postoperative day (POD) 7 and 14. It was found that ADSCs significantly reduced acute rejection and improved the allograft's survival times (median, 24days). Liver function, as assessed by the levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin, as well as liver apoptosis was significantly alleviated in the ADSC group compared with the control group. In addition, ADSC therapy markedly promoted the expression of PCNA in the allograft. Furthermore, levels of interleukin (IL)-10 and transforming growth factor (TGF)-β1 were significantly elevated, whereas those of IL-2 and IL-17 levels were significantly reduced in the ADSC group when compared to the control group. Moreover, flow cytometry analysis revealed that peripheral Tregs had been significantly increased by the infusion of ADSCs. These results demonstrate that implanted autologous ADSCs improve allogeneic reduced size liver allograft outcomes by attenuating acute rejection and reducing inflammatory responses, as well as enhancing liver regeneration. •ADSC improve allogeneic reduced size liver allograft survival.•ADSC therapy after 50% RSLT inhibits hepatocyte apoptosis, enhances hepatocyte regeneration, and attenuates acute rejection.•ADSC can exert their immunosuppressive effects is by inducing the production of Tregs.
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2Adipose Tissue - cytology
3Adipose-derived mesenchymal stem cells
4Analysis
5Animals
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7Cells, Cultured
8Cytokines - metabolism
9Enzymes
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12Histochemistry
13Immune Tolerance
14Interleukins
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18Liver Transplantation
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20Medical research
21Medicine, Experimental
22Mesenchymal Stem Cell Transplantation
23Mesenchymal Stromal Cells - physiology
24Organ Size
25Phosphates
26Rats
27Rats, Inbred BN
28Rats, Inbred Lew
29Recovery of Function
30Reduced size liver transplantation
31Stem cells
32T cells
33T-Lymphocytes, Regulatory - immunology
34Transforming growth factors
35Transplantation
36Transplantation, Homologous
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35Transplantation
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abstractAdipose-derived mesenchymal stem cells (ADSCs) possess a liver regeneration capacity and immunosuppressive activity and hold promise in autologous cell-based technology. This study aimed to determine whether autologous ADSCs can improve outcomes in the rat reduced size liver transplantation model. Allogeneic 50% orthotopic liver transplantation followed by administration of autologous ADSCs delivered into the portal vein system was conducted in LEW donor rats and BN recipient rats with phosphate buffered solution (PBS) infusion used as the control. Liver grafts and recipient serum were obtained. We assessed histopathology, regeneration, apoptosis, serum liver enzymes, serum cytokines, and circulating regulatory T cells (Tregs) on postoperative day (POD) 7 and 14. It was found that ADSCs significantly reduced acute rejection and improved the allograft's survival times (median, 24days). Liver function, as assessed by the levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin, as well as liver apoptosis was significantly alleviated in the ADSC group compared with the control group. In addition, ADSC therapy markedly promoted the expression of PCNA in the allograft. Furthermore, levels of interleukin (IL)-10 and transforming growth factor (TGF)-β1 were significantly elevated, whereas those of IL-2 and IL-17 levels were significantly reduced in the ADSC group when compared to the control group. Moreover, flow cytometry analysis revealed that peripheral Tregs had been significantly increased by the infusion of ADSCs. These results demonstrate that implanted autologous ADSCs improve allogeneic reduced size liver allograft outcomes by attenuating acute rejection and reducing inflammatory responses, as well as enhancing liver regeneration. •ADSC improve allogeneic reduced size liver allograft survival.•ADSC therapy after 50% RSLT inhibits hepatocyte apoptosis, enhances hepatocyte regeneration, and attenuates acute rejection.•ADSC can exert their immunosuppressive effects is by inducing the production of Tregs.
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pubElsevier B.V
pmid28778713
doi10.1016/j.trim.2017.07.005