Cell and cell-derivative-based therapy for liver diseases: current approaches and future promises

ABSTRACT

Introduction

According to the recent updates from World Health Organization, liver diseases are the 12th most common cause of mortality. Currently, orthotopic liver transplantation (OLT) is the most effective and the only treatment for end-stage liver diseases. Owing to several shortcomings like finite numbers of healthy organ donors, lifelong immunosuppression, and complexity of the procedure, cell and cell-derivatives therapies have emerged as a potential therapeutic alternative for liver diseases. Various cell types and therapies have been proposed and their therapeutic effects evaluated in preclinical or clinical studies, including hepatocytes, hepatocyte-like cells (HLCs) derived from stem cells, human liver stem cells (HLSCs), combination therapies with various types of cells, organoids, and implantable cell-biomaterial constructs with synthetic and natural polymers or even decellularized extracellular matrix (ECM).

Areas covered

In this review, we highlighted the current status of cell and cell-derivative-based therapies for liver diseases. Furthermore, we discussed future prospects of using HLCs, liver organoids, and their combination therapies.

Expert opinion

Promising application of stem cell-based techniques including iPSC technology has been integrated into novel techniques such as gene editing, directed differentiation, and organoid technology. iPSCs offer promising prospects to represent novel therapeutic strategies and modeling liver diseases.

KEYWORDS:

• Primary hepatocyte
• liver organoids
• mesenchymal stromal cells
• pluripotent stem cells
• extracellular vesicles
• liver cell therapy

Article highlights

• Several liver disorders can be treated using cell-based therapies.

• MScs have some possible therapeutic mechanisms in liver diseases.

• iPSCs-derived liver organoid could be utilized as transplantable units for treatment of liver diseases.

• Biomaterial-combined cell therapies have the potential to extend the therapeutic impact of transplanted liver cells by providing 3D organization.

• EVs administration could improve liver regeneration and function by transferring bioactive molecules.

Declaration of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.