Role of Artificial Cells in the Treatment of Liver Disease

Keywords

Artificial cell, biomimetic, cell therapy, liver diseases, stem cell, gene therapy, cell transplant, bioartificial liver, regenerative medicine, cell therapy.

Introduction

Liver diseases have become an increasing health burden accounting for millions of deaths every year globally. Standard therapies including liver transplant and cell therapy offer a promising treatment for liver diseases, but they also suffer limitations such as adverse immune reactions and lack of long-term efficacy. Artificial cells that mimic certain functions of a living cell have emerged as a new strategy to overcome some of the challenges that liver cell therapy faces at present. Artificial cells have demonstrated advantages in long-term storage, targeting capability, and tunable features.

An overview of the recent progress in developing artificial cells and their potential applications in liver disease treatment, including the design of artificial cells and their biomimicking functions, two systems that mimic cell surface properties such as cell membrane-coated artificial cells and synthetic lipid-based artificial cells, and cell microencapsulation strategy, also the challenges and future perspectives of artificial cells.

Key Points

The goals of liver support therapy include the following:

• To provide detoxification and synthetic function during liver failure.

• To remove or reduce the production of proinflammatory cytokines to correct the systemic inflammatory response of liver failure.

• To stimulate the regeneration of the injured liver and increase the likelihood of spontaneous recovery.

• There is a large unmet need for a liver support device because of the shortage of organs for liver transplantation and the risks of major surgery.

• Liver support devices can be divided into 2 groups: purely mechanical artificial devices and cell-based bioartificial devices. Both provide detoxification, but bioartificial liver devices provide the option of synthetic function and biotransformation activities that are not possible with a purely mechanical device.

• An abundant high-quality supply of human hepatocytes is not currently available for liver cell therapy. However, such a supply is essential for successful bioartificial liver therapy. Novel options are under development for the unlimited production of high-quality human hepatocytes.

Liver is the largest organ in the human body that performs many fundamental functions, including filtering blood, detoxifying wastes, and toxins, synthesizing proteins and glycogen, metabolizing lipids, excreting bile for digestion, storing, and delivering nutrients, and breakdown of hormones.

Many people suffer from liver diseases including nonalcoholic fatty liver disease (NAFLD), hepatitis, alcohol-related liver disease (ARLD), drug-induced liver injury (DILI), and primary biliary cholangitis (PBC). Although the liver can regenerate, liver diseases often cause irreversible liver damage and loss of functions, which often lead to fibrosis or cirrhosis, acute liver failure, chronic liver failure, and even hepatocellular carcinoma.

Liver transplants save many lives, but it only meets 10% of the worldwide needs because of the shortage of liver donors.

Cells are the basic units of life, are very complex systems possessing unique structures and distinct functions. Cell therapy represents a promising alternative treatment to promote liver regeneration and offers some attractive advantages over traditional liver transplantation, such as less immune invasion and accessible cell sources.

Various types of cells have been proved to be effective in treating liver diseases in preclinical models, including hepatocytes, macrophages, and stem cells such as mesenchymal stem cells, hematopoietic stem cells, endothelial progenitor cells. Stem cell therapy as regenerative medicine is promising with its ability to differentiate hepatocyte-like cells to repair the liver.

Mesenchymal stem cells (MSCs) are the most widely used stem cells in clinical and preclinical studies for the treatment of liver disease, including liver cirrhosis, liver failure, and complications of liver transplantation. The design, assembly, and behavior of artificial cells and their continuing development to improve the efficacy and safety of their applications for the treatment of liver diseases.

Functions of Artificial Cells

The different functions of artificial cells related to clinical applications include membrane features, metabolic reactions, and cell communication.

Mimicking Cell Surface Properties

In this section, artificial cells that mimic cell surface properties are introduced with two key strategies: cell membrane-coated AC such as red blood cell membrane coated, cancer cell membrane coated, stem cell membrane coated, and macrophage membrane coated, and synthetic lipid-coated AC.

Cell Microencapsulation

A semi-membrane-based artificial cell has been developed to mimic cells or organelles, also known as cell microencapsulation. Cell microencapsulation technology refers to the technique to encapsulate living cells in microcapsules made from membrane-like materials.

Potential Applications of Stem Cells in Liver Diseases

• Hereditary Liver Diseases
• Acute Liver Failure (ALF)
• Cirrhosis
• Liver Cancer
• Liver Transplantation

Conclusion

Present treatment for liver diseases faces challenges associated with immune invasion, long-term efficacy, lack of targeting, and so on. Compared to conventional therapeutics, artificial cells have the potential to improve treatment efficacy for liver disease by mimicking the structure and function of natural cells including cell metabolic reactions, cell communication, and cell surface properties.

The principle of artificial cells was a very novel idea when it was first proposed, and it took time to extend this principle for use in cell and organ replacements.

For example, encapsulated cells are being studied for the treatment of diabetes, liver failure and kidney failure. Artificial cells containing enzymes are being developed for clinical trial in hereditary enzyme deficiency diseases and other diseases. The artificial cell is also being investigated for drug delivery and for other uses in biotechnology, chemical engineering, and medicine.