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Future Approaches in Liver Disorders: Regenerative Medicine

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Liver Diseases

Abstract

End-stage liver disease benefits only from liver transplantation. As we shall see, the emerging field of regenerative medicine offers novel approaches to liver disease treatment based on a remarkable progress in basic biomedical research during the last 20–30 years. In this context, the major methods of regenerative medicine are cell therapy, tissue/organ engineering and bioartificial liver with promising results. At the present time, cell therapy is an important tool to evaluate liver regeneration, hepatoxicity of xenobiotics by CYP enzymes, and drug interactions. Moreover, bioartificial livers can remove the problematic lack of donor liver and allow disease modeling. Ultimately, advancements in liver genome editing might treat either hereditary monogenic liver disorders or viral hepatitis. Herein, we discuss the basic knowledge of liver regeneration and highlight the current methods of liver regenerative medicine.

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Abbreviations

ATF5:

Activating Transcription Factor 5

BAL:

bioartificial liver

BMPs:

bone morphogenetic protein

CEBPA:

CCAAT/enhancer binding protein (C/EBP) alpha

CYP:

cytochrome P450

DNMTi:

DNA methylation inhibitor

EGF:

epidermal growth factor

ESCs:

embryonic stem cells

FGF:

fibroblast growth factor

FGF:

fibroblast growth factor

FOXA1:

Forkhead Box A1

FOXA2:

Forkhead Box A2

FOXA3:

Forkhead Box A3

G-CSF:

Granulocyte-colony stimulating factor

HDACi:

histone deacetylase inhibitor

HGF:

hepatocyte growth factor

HLCs:

Hepatocyte like-cells

HNF1A:

hepatocyte nuclear factor 1 alpha or hepatocyte nuclear factor 1 homeobox alpha

HNF4A:

hepatocyte nuclear factor 4 alpha

HSCs:

hematopoietic stem cells

IL-6:

interleukin-6

iPSCs:

induced pluripotent stem cells

LSPCs:

liver stem/progenitor cells

MELD:

Model For End-Stage Liver Disease

MIR122:

MicroRNA 122

MSCs:

mesenchymal stem cells

NASH:

Nonalcoholic steatohepatitis

OSM:

oncostatin M

PPARα:

peroxisome proliferator-activated receptor α

PSCs:

pluripotent stem cells

TGFα:

transforming growth factor

TNFα:

tumor necrosis factor alpha

β-PDGRR:

platelet-derived growth factors

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Author information

Authors and Affiliations

  1. Central Military Emergency University Hospital “Dr. Carol Davila”, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania

    Mariana Jinga & Vasile Daniel Balaban

  2. “Prof. C.C. Iliescu” Emergency Institute for Cardiovascular Diseases, Bucharest, Romania

    Ecaterina Bontas

  3. Faculty of Medicine, “Carol Davila” Central Military Emergency University Hospital, “Titu Maiorescu” University, Bucharest, Romania

    Ion C. Tintoiu

Authors
  1. Mariana Jinga
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  2. Vasile Daniel Balaban
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  3. Ecaterina Bontas
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  4. Ion C. Tintoiu
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Editor information

Editors and Affiliations

  1. Faculty of Medicine, “Titu Maiorescu” University, Central Military Emergency University Hospital “Dr. Carol Davila”, Bucharest, Romania

    Florentina Radu-Ionita

  2. New Jersey Medical School, Rutgers University New Jersey Medical School, Newark, NJ, USA

    Nikolaos T. Pyrsopoulos

  3. Carol Davila University of Medicine and Pharmacy, Central Military Emergency University Hospital “Dr. Carol Davila”, Bucharest, Romania

    Mariana Jinga

  4. Faculty of Medicine, “Titu Maiorescu” University, Central Military Emergency University Hospital “Dr. Carol Davila”, Bucharest, Romania

    Ion C. Tintoiu

  5. Medical Radiation Sciences, Curtin University, Perth, WA, Australia

    Zhonghua Sun

  6. “Prof. C.C. Iliescu” Emergency Institute for Cardiovascular Diseases, Bucharest, Romania

    Ecaterina Bontas

Self Study

Self Study

1.1 Questions

  1. 1.

    Which statement is true?

    1. (a)

      An important tool to evaluate liver regeneration is cell therapy.

    2. (b)

      Hepatocyte like-cells are manufactured only from human ESCs.

    3. (c)

      Hepatocyte like-cells from human ESCs are obtained from whole blastocyst.

    4. (d)

      Co-culturing uses only human umbilical vein endothelial cells.

  2. 2.

    Which statement/statements is/are true?

    1. (a)

      Microencapsulation technique defines the fixation of hepatocytes into a semipermeable polymer.

    2. (b)

      BAL systems are a temporary option in therapy of acute liver failure.

    3. (c)

      BAL systems contain hepatocytes located in a mechanical artificial liver support device.

    4. (d)

      Stem cell transplantation together with gene therapy can correct the metabolic deficits of inherited liver disease on long time.

1.2 Answers

  1. 1.

    Which statement is true?

    1. (a)

      Correct. Cell-based therapy is an important tool to evaluate liver regeneration, hepatotoxicity or metabolism of xenobiotics by CYP enzymes, drug interactions.

    2. (b)

      Hepatocyte like-cells are generated in vitro, from human pluripotent stem cells (PSCs), from human ESCs, iPSCs, gestational stem cells, and mesenchymal stem cells (MSCs).

    3. (c)

      Hepatocyte like-cells from human ESCs are obtained from inner part of blastocyst.

    4. (d)

      Co-culturing uses human MSCs, HUVEC-human umbilical vein endothelial cells, and human iPSCs-derived human endodermal cells.

  2. 2.

    Which statement/statements is/are true?

    1. (a)

      Correct.

    2. (b)

      Correct.

    3. (c)

      Correct.

    4. (d)

      Correct.

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Jinga, M., Balaban, V.D., Bontas, E., Tintoiu, I.C. (2020). Future Approaches in Liver Disorders: Regenerative Medicine. In: Radu-Ionita, F., Pyrsopoulos, N., Jinga, M., Tintoiu, I., Sun, Z., Bontas, E. (eds) Liver Diseases. Springer, Cham. https://doi.org/10.1007/978-3-030-24432-3_74

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  • DOI: https://doi.org/10.1007/978-3-030-24432-3_74

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  • Online ISBN: 978-3-030-24432-3

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