Liver cell therapy: is this the end of the beginning?

Alwahsh, Salamah Mohammad; Rashidi, Hassan; Hay, David C.

doi:10.1007/s00018-017-2713-8

Cited by 61 publications

(41 citation statements)

References 196 publications

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“…While donor hepatocytes have been used to successfully treat metabolic liver disease (Alwahsh et al 2018 ), the graft is eventually lost. This is further compounded by the scarcity of human hepatocytes.…”

Section: Introductionmentioning

confidence: 99%

3D human liver tissue from pluripotent stem cells displays stable phenotype in vitro and supports compromised liver function in vivo

et al. 2018

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Liver disease is an escalating global health issue. While liver transplantation is an effective mode of therapy, patient mortality has increased due to the shortage of donor organs. Developing renewable sources of human liver tissue is therefore attractive. Pluripotent stem cell-derived liver tissue represents a potential alternative to cadaver derived hepatocytes and whole organ transplant. At present, two-dimensional differentiation procedures deliver tissue lacking certain functions and long-term stability. Efforts to overcome these limiting factors have led to the building of three-dimensional (3D) cellular aggregates. Although enabling for the field, their widespread application is limited due to their reliance on variable biological components. Our studies focused on the development of 3D liver tissue under defined conditions. In vitro generated 3D tissues exhibited stable phenotype for over 1 year in culture, providing an attractive resource for long-term in vitro studies. Moreover, 3D derived tissue provided critical liver support in two animal models, including immunocompetent recipients. Therefore, we believe that our study provides stable human tissue to better model liver biology ‘in the dish’, and in the future may permit the support of compromised liver function in humans.Electronic supplementary materialThe online version of this article (10.1007/s00204-018-2280-2) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

3D human liver tissue from pluripotent stem cells displays stable phenotype in vitro and supports compromised liver function in vivo

et al. 2018

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“…Patients with inborn liver-based metabolic disorders are good candidates for cell transplantation, presenting only defects in enzymes or transport proteins for which even partial correction will significantly improve a patient's condition. Successful clinical trials have been reported in treating liver-based metabolic disorders in pediatric patients, and numerous studies are currently being carried out in order to improve cell availability and safety as well as medical procedures [32,33]. Nevertheless, all these studies allowed for the identification of some critical parameters for the optimal organ repopulation by transplanted cells and the anticipated clinical outcome.…”

Section: Cell Therapy: Transplantation Of Isolated Cellmentioning

confidence: 99%

Pluripotent-Stem-Cell-Derived Hepatic Cells: Hepatocytes and Organoids for Liver Therapy and Regeneration

Messina

Luce

Hussein

et al. 2020

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The liver is a very complex organ that ensures numerous functions; it is thus susceptible to multiple types of damage and dysfunction. Since 1983, orthotopic liver transplantation (OLT) has been considered the only medical solution available to patients when most of their liver function is lost. Unfortunately, the number of patients waiting for OLT is worryingly increasing, and extracorporeal liver support devices are not yet able to counteract the problem. In this review, the current and expected methodologies in liver regeneration are briefly analyzed. In particular, human pluripotent stem cells (hPSCs) as a source of hepatic cells for liver therapy and regeneration are discussed. Principles of hPSC differentiation into hepatocytes are explored, along with the current limitations that have led to the development of 3D culture systems and organoid production. Expected applications of these organoids are discussed with particular attention paid to bio artificial liver (BAL) devices and liver bio-fabrication.

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“…The ECM plays a crucial role in cellular organization and function. 61 Several approaches have been investigated, including co-culture and the development of 3-dimensional (3D) systems. 62,63 It is possible that cells grown in 3D systems would behave more like cells in vivo and be implanted directly.…”

Section: Tissue Engineeringmentioning

confidence: 99%

Mesenchymal Stem Cells for the Treatment of Liver Disease: Present and Perspectives

et al. 2020

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Mesenchymal stem cell transplantation is an emerging therapy for treating chronic liver diseases. The potential of this treatment has been evaluated in preclinical and clinical studies. Although the mechanisms of mesenchymal stem cell transplantation are still not completely understood, accumulating evidence has revealed that their immunomodulation, differentiation, and antifibrotic properties play a crucial role in liver regeneration. The safety and therapeutic effects of mesenchymal stem cells in patients with chronic liver disease have been observed in many clinical studies. However, only modest improvements have been seen, partly because of the limited feasibility of transplanted cells at present. Here, we discuss several strategies targeted at improving viable cell engraftment and the potential challenges in the use of extracellular vesicle-based therapies for liver disease in the future.

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Liver cell therapy: is this the end of the beginning?

Cited by 61 publications

References 196 publications

3D human liver tissue from pluripotent stem cells displays stable phenotype in vitro and supports compromised liver function in vivo

3D human liver tissue from pluripotent stem cells displays stable phenotype in vitro and supports compromised liver function in vivo

Pluripotent-Stem-Cell-Derived Hepatic Cells: Hepatocytes and Organoids for Liver Therapy and Regeneration

Mesenchymal Stem Cells for the Treatment of Liver Disease: Present and Perspectives

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