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      Adipose-Derived Stem Cell Transplantation Attenuates Inflammation and Promotes Liver Regeneration after Ischemia-Reperfusion and Hemihepatectomy in Swine

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          Abstract

          Aim

          To study the anti-inflammatory and liver regenerative effects of adipose-derived mesenchymal stem cells (ADSCs) on a porcine model of ischemia-reperfusion (IR) and hemihepatectomy.

          Methods

          Eighteen healthy Bama miniature pigs were randomly divided into the sham-operated (sham), untreated IR injury (IRI), and ADSC-transplanted (ADSC) groups. Hepatic IR was established by laparoscopic hemihepatectomy. ADSCs were transplanted directly into the liver parenchyma after the surgery. Hepatic inflammation and liver regeneration were evaluated by histopathological examination and assessment of relevant cytokines and other factors.

          Results

          ADSC transplantation successfully ameliorated the IRI-induced histopathological damage and the high levels of pro-inflammatory cytokines like IL-1 β, IL-6, and TNF- α. In addition, the ADSCs enhanced the expression of the anti-inflammatory IL-10, regenerative factors including HGF, Cyclin D1, and proliferating cell nuclear antigen (PCNA), and angiogenic factors like VEGF, ANG-1, and ANG-2.

          Conclusions

          ADSCs attenuated the hepatic IRI-induced inflammatory response and promoted liver regeneration.

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          Most cited references48

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          Liver regeneration.

          George Michalopoulos (2007)
          Liver regeneration after partial hepatectomy is a very complex and well-orchestrated phenomenon. It is carried out by the participation of all mature liver cell types. The process is associated with signaling cascades involving growth factors, cytokines, matrix remodeling, and several feedbacks of stimulation and inhibition of growth related signals. Liver manages to restore any lost mass and adjust its size to that of the organism, while at the same time providing full support for body homeostasis during the entire regenerative process. In situations when hepatocytes or biliary cells are blocked from regeneration, these cell types can function as facultative stem cells for each other.
          Article 0 comments Cited 437 times – based on 0 reviews     Review now
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            Neutrophil infiltration as an important factor in liver ischemia and reperfusion injury. Modulating effects of FK506 and cyclosporine.

            S. Suzuki, L H Toledo-Pereyra, Karina Rodriguez … (1993)
            To examine the role of neutrophils, their presence and the degree of infiltration, as important determinants of ischemia and reperfusion injury of the liver, male Sprague-Dawley rats were subjected to 60 and 90 min of total-liver ischemia. The presence of neutrophils, assessed by the measurement of liver tissue myeloperoxidase (MPO), and the degree of neutrophil liver infiltration, determined by the naphthol AS-D chloroacetate esterase technique, correlated well with animal survival and response to FK506 and cyclosporine administration. Lipid peroxidation, measured by the malondialdehyde (MDA) test in liver tissue, was another factor closely linked with liver function and survival. Pretreatment with FK506 (0.3 mg/kg) and CsA (5 mg/kg) was given at 4 hr and 1 hr before ischemia and at the time of reperfusion. Control ischemic animals showed increased neutrophil liver infiltration, high MPO and MDA liver levels, and diminished overall survival. FK506 and CsA-treated animals had better survival and diminished neutrophil liver infiltration, as well as MPO and MDA levels. The mechanism by which FK506 and CsA protected the animals from severe liver ischemic injury is unknown. Our data indicated that the presence and the degree of infiltration of neutrophils were important components of liver ischemia/reperfusion injury in the rat. So it is possible that one of the fundamental effects of the FK506 and CsA might be through the inhibition of the presence and infiltration of neutrophils in liver tissue.
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              The angiogenic properties of mesenchymal stem/stromal cells and their therapeutic potential.

              Francesca Gullo, Cheen Khoo, D. Markeson … (2012)
              Blood vessel formation is fundamental to development, while its dysregulation can contribute to serious disease. Expectations are that hundreds of millions of individuals will benefit from therapeutic developments in vascular biology. MSCs are central to the three main vascular repair mechanisms. Key recent published literature and ClinicalTrials.gov. MSCs are heterogeneous, containing multi-lineage stem and partly differentiated progenitor cells, and are easily expandable ex vivo. There is no single marker defining native MSCs in vivo. Their phenotype is strongly determined by their specific microenvironment. Bone marrow MSCs have skeletal stem cell properties. Having a perivascular/vascular location, they contribute to vascular formation and function and might be harnessed to regenerate a blood supply to injured tissues. These include MSC origin, phenotype and location in vivo and their ability to differentiate into functional cardiomyocytes and endothelial cells or act as vascular stem cells. In addition their efficacy, safety and potency in clinical trials in relation to cell source, dose, delivery route, passage and timing of administration, but probably even more on the local preconditioning and the mechanisms by which they exert their effects. Understanding the origin and the regenerative environment of MSCs, and manipulating their homing properties, proliferative ability and functionality through drug discovery and reprogramming strategies are important for their efficacy in vascular repair for regenerative medicine therapies and tissue engineering approaches. Characterization of MSCs' in vivo origins and biological properties in relation to their localization within tissue niches, reprogramming strategies and newer imaging/bioengineering approaches.
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                Author and article information

                Contributors
                Hongbin Wang:
                ORCID: https://orcid.org/0000-0002-4454-3328
                Journal
                Journal ID (nlm-ta): Stem Cells Int
                Journal ID (iso-abbrev): Stem Cells Int
                Journal ID (publisher-id): SCI
                Title: Stem Cells International
                Publisher: Hindawi
                ISSN (Print): 1687-966X
                ISSN (Electronic): 1687-9678
                Publication date Collection: 2019
                Publication date (Electronic): 18 November 2019
                Volume: 2019
                Electronic Location Identifier: 2489584
                Affiliations
                1Department of Veterinary Surgery, College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China
                2Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, Harbin 150030, China
                Author notes

                Academic Editor: Francisco J. Rodríguez-Lozano

                Author information
                https://orcid.org/0000-0001-7055-3485
                https://orcid.org/0000-0002-4454-3328
                Article
                DOI: 10.1155/2019/2489584
                PMC ID: 6885808
                PubMed ID: 31827526
                SO-VID: 57ab6501-f199-44e8-990f-e14940977259
                Copyright © Copyright © 2019 Zhihui Jiao et al.
                License:

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 12 July 2019
                Date revision received : 17 September 2019
                Date accepted : 23 October 2019
                Funding
                Funded by: National Natural Science Foundation of China
                Award ID: 31772807
                Award ID: 31472245
                Categories
                Subject: Research Article

                ScienceOpen disciplines: Molecular medicine
                Data availability:
                ScienceOpen disciplines: Molecular medicine

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