Stem Cell Therapies for Treatment of Liver Disease

Nicolas, Clara T.; Wang, Yujia; Luebke-Wheeler, Jennifer; Nyberg, Scott L.

doi:10.3390/biomedicines4010002

Cited by 37 publications

(37 citation statements)

References 152 publications

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“…Recent evidences indicate that LPCs isolated from adult healthy mouse liver are important source of new mature hepatocytes for tissue maintenance and repair in vivo, and for regenerative medicine ex vivo [26,27]. Understanding the mechanism that LPCs differentiation into hepatocytes may allow for novel induction strategies for chronic liver disease [28]. Here, we used rat liver progenitor cell WB-F344 as LPC cell model and HGF as inducer to simulate the process of LPCs hepatic differentiation [29].…”

Section: Discussionmentioning

confidence: 99%

Mir-382 Promotes Differentiation of Rat Liver Progenitor Cell WB-F344 by Targeting Ezh2

Zheng

Zhou

et al. 2018

Cell Physiol Biochem

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Background/Aims: Liver progenitor cells (LPCs) were considered as a promising hepatocyte source of cell therapy for liver disease due to their self-renewal and differentiation capacities, while little is known about the mechanism of LPC differentiate into hepatocytes. This study aims to explore the effect of miR-382, a member of Dlk1-Dio3 microRNA cluster, during hepatic differentiation from LPCs. Methods: In this study, we used rat liver progenitor cell WB-F344 as LPC cell model and HGF as inducer to simulate the process of LPCs hepatic differentiation, then microRNAs were quantified by qPCR. Next, WB-F344 cell was transfected with miR-382 mimics, then hepatocyte cell trait was characterized by multiple experiments, including that periodic acid schiff staining and cellular uptake and excretion of indocyanine green to evaluate the hepatocellular function, qPCR and Western Blotting analysis to detect the hepatocyte-specific markers (ALB, Ttr, Apo E and AFP) and transmission electron microscopy to observe the hepatocellular morphology. Moreover, Luciferase reporter assay was used to determine whether Ezh2 is the direct target of miR-382. Results: We found that miR-382 increased gradually and was inversely correlated with the potential target, Ezh2, during WB-F344 hepatic differentiation. In addition, functional studies indicated that miR-382 increased the level of hepatocyte-specific genes. Conclusions: This study demonstrates that miR-382 may be a novel regulator of LPCs differentiation by targeting Ezh2.

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Section: Discussionmentioning

confidence: 99%

Mir-382 Promotes Differentiation of Rat Liver Progenitor Cell WB-F344 by Targeting Ezh2

Zheng

Zhou

et al. 2018

Cell Physiol Biochem

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“…The development of an implantable engineered liver device, for liver regeneration application, represents an innovative approach to surmount the limitations of liver cell therapy and to provide engineered liver microtissues able to sustain and regenerate liver functions. This approach aimed to be particularly critical for patients with severe liver diseases, for whom whole liver transplantation represented the only presently existing treatment opportunity.…”

Section: Conventional Versus Advanced Processing Technologies For LIVmentioning

confidence: 99%

Advanced Biomaterials and Processing Methods for Liver Regeneration: State‐of‐the‐Art and Future Trends

Morais

Vieira

Zhao

et al. 2020

Adv Healthcare Materials

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Liver diseases contribute markedly to the global burden of mortality and disease. The limited organ disposal for orthotopic liver transplantation results in a continuing need for alternative strategies. Over the past years, important progress has been made in the field of tissue engineering (TE). Many of the early trials to improve the development of an engineered tissue construct are based on seeding cells onto biomaterial scaffolds. Nowadays, several TE approaches have been developed and are applied to one vital organ: the liver. Essential elements must be considered in liver TE—cells and culturing systems, bioactive agents or growth factors (GF), and biomaterials and processing methods. The potential of hepatocytes, mesenchymal stem cells, and others as cell sources is demonstrated. They need engineered biomaterial‐based scaffolds with perfect biocompatibility and bioactivity to support cell proliferation and hepatic differentiation as well as allowing extracellular matrix deposition and vascularization. Moreover, they require a microenvironment provided using conventional or advanced processing technologies in order to supply oxygen, nutrients, and GF. Herein the biomaterials and the conventional and advanced processing technologies, including cell‐sheets process, 3D bioprinting, and microfluidic systems, as well as the future trends in these major fields are discussed.

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“…Isolated primary hepatocytes were the first and most obvious candidate for use in cell therapy, but they have several limitations related to both the nature of the cell and the scarcity of its source. Hepatocytes are not easily cultured in vitro and are susceptible to freeze‐thaw damage . The most important restriction to their use, however, is the difficulty that isolation of a sufficient quantity of metabolically active, high quality cells presents .…”

Section: Use Of Primary Hepatocytes Versus Stem Cellsmentioning

confidence: 99%

Concise Review: Liver Regenerative Medicine: From Hepatocyte Transplantation to Bioartificial Livers and Bioengineered Grafts

et al. 2016

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Donor organ shortage is the main limitation to liver transplantation as a treatment for end-stage liver disease (ESLD) and acute liver failure (ALF). Liver regenerative medicine may in the future offer an alternative form of therapy for these diseases, be it through cell transplantation, bioartificial liver (BAL) devices, or bioengineered whole organ liver transplantation. All three strategies have shown promising results in the past decade. However, before they are incorporated into widespread clinical practice, the ideal cell type for each treatment modality must be found, and an adequate amount of metabolically active, functional cells must be able to be produced. Research is ongoing in hepatocyte expansion techniques, use of xenogeneic cells, and differentiation of stem cell-derived hepatocyte-like cells (HLCs). HLCs are a few steps away from clinical application, but may be very useful in individualized drug development and toxicity testing, as well as disease modeling. Finally, safety concerns including tumorigenicity and xenozoonosis must also be addressed before cell transplantation, BAL devices, and bioengineered livers occupy their clinical niche. This review aims to highlight the most recent advances and provide an updated view of the current state of affairs in the field of liver regenerative medicine.

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Stem Cell Therapies for Treatment of Liver Disease

Cited by 37 publications

References 152 publications

Mir-382 Promotes Differentiation of Rat Liver Progenitor Cell WB-F344 by Targeting Ezh2

Mir-382 Promotes Differentiation of Rat Liver Progenitor Cell WB-F344 by Targeting Ezh2

Advanced Biomaterials and Processing Methods for Liver Regeneration: State‐of‐the‐Art and Future Trends

Concise Review: Liver Regenerative Medicine: From Hepatocyte Transplantation to Bioartificial Livers and Bioengineered Grafts

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