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Review
. 2020 Feb 7;9(2):386.
doi: 10.3390/cells9020386.

Evolving Cell-Based and Cell-Free Clinical Strategies for Treating Severe Human Liver Diseases

Viviana Cernigliaro  1   2 , Rossella Peluso  1   2 , Beatrice Zedda  1   2 , Lorenzo Silengo  3 , Emanuela Tolosano  3 , Rinaldo Pellicano  4 , Fiorella Altruda  3 , Sharmila Fagoonee  5
Affiliations
Review

Evolving Cell-Based and Cell-Free Clinical Strategies for Treating Severe Human Liver Diseases

Viviana Cernigliaro et al. Cells. .

Abstract

Liver diseases represent a major global health issue, and currently, liver transplantation is the only viable alternative to reduce mortality rates in patients with end-stage liver diseases. However, scarcity of donor organs and risk of recidivism requiring a re-transplantation remain major obstacles. Hence, much hope has turned towards cell-based therapy. Hepatocyte-like cells obtained from embryonic stem cells or adult stem cells bearing multipotent or pluripotent characteristics, as well as cell-based systems, such as organoids, bio-artificial liver devices, bioscaffolds and organ printing are indeed promising. New approaches based on extracellular vesicles are also being investigated as cell substitutes. Extracellular vesicles, through the transfer of bioactive molecules, can modulate liver regeneration and restore hepatic function. This review provides an update on the current state-of-art cell-based and cell-free strategies as alternatives to liver transplantation for patients with end-stage liver diseases.

Keywords: cell therapy; extracellular vesicles; liver diseases; organ printing; organoids; scaffolds; transplantation.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Sources of hepatic-like cells (HLCs) for stem cell therapy in liver disease. HLCs can be differentiated from embryonic stem cells (ESCs) derived from the inner cell mass of blastocysts, or from adult stem cells (AdSCs). The main types of AdSCs used for cell therapy are: mesenchymal stem/stromal cells (MSCs) isolated from blood, adipose tissue, cartilage, bone marrow and synovial membrane; hematopoietic stem cells (HSCs) found in the bone marrow and umbilical cord blood; biliary tree stem/progenitor cells (BTSCs) derived from the peribiliary glands of the adult and fetal human biliary tree or from the crypts of the gallbladder; endothelial progenitor cells (EPCs) taken from peripheral vessels and from bone marrow; liver stem cells (LSCs) localised in the liver. HLCs can be also obtained from induced pluripotent stem cells (iPSCs) obtained by reprogramming of adults cells by specific growth factors or spermatogonial stem cells (SSCs) derived from testis.
Figure 2
Figure 2
The mechanism of action of stem cells in the treatment of liver diseases. Stem cell injection may act in several ways in supporting liver repair. Functional stem cells may substitute diseased liver cells and at the same time provide the wild-type gene in case of genetic deficiencies, hence serving as a platform for gene therapy. Stem cells also release soluble factors such as growth factors and cytokines/chemokines to dampen liver injury. Extracellular vesicles (EVs) harbouring biomolecules with restorative properties are also produced by stem cells and participate in liver regenerative process.
Figure 3
Figure 3
A Bioartificial Liver (BAL) system: Patient blood is taken from the venous circulation and separated from plasma, which flows into a reservoir through a pump system. The plasma then goes into a bioreactor inoculated with living cells and returns to the patient after filtration and rejoins the blood.
Figure 4
Figure 4
Action of EVs on liver repair. Upon injury, hepatocytes release EVs containing restorative non-coding RNAs, proteins and lipids that induce the regenerative process in the liver by enhancing survival and proliferation of resident cells, neovascularisation, and by modulating niche homeostasis. Stem cell therapy potentiates this process by providing EVs with anti-inflammatory and immunomodulatory properties to the damaged liver. These EVs may have anti-fibrotic effects and prevent cytotoxicity in the liver, hence contributing to slowing the progression to end-stage liver diseases.
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References

    1. Asrani S.K., Devarbhavi H., Eaton J., Kamath P.S. Burden of liver diseases in the world. J. Hepatol. 2019;70:151–171. doi: 10.1016/j.jhep.2018.09.014. - DOI - PubMed
    1. Brown S.A., Axenfeld E., Stonesifer E.G., Hutson W., Hanish S., Raufman J.P., Urrunaga N.H. Current and prospective therapies for acute liver failure. Dis Mon. 2018;64:493–522. doi: 10.1016/j.disamonth.2018.04.002. - DOI - PubMed
    1. Testino G., Leone S., Fagoonee S., Pellicano R. Alcoholic liver fibrosis: Detection and treatment. Minerva Med. 2018;109:457–471. doi: 10.23736/S0026-4806.18.05844-5. - DOI - PubMed
    1. Toniutto P., Bitetto D., Fornasiere E., Fumolo E. Challenges and future developments in liver transplantation. Minerva Gastroenterol. Dietol. 2019;65:136–152. doi: 10.23736/S1121-421X.18.02529-1. - DOI - PubMed
    1. Carmody I.C., Romano J., Bohorquez H., Bugeaud E., Bruce D.S., Cohen A.J., Seal J., Reichman T.W., Loss G.E. Novel Biliary Reconstruction Techniques During Liver Transplantation. Ochsner J. 2017;17:42–45. - PMC - PubMed

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