AN INTRODUCTION TO LIVER TISSUE ENGINEERING
Author: Mridula Vats
The liver has an essential role in the health and lifespan of humans due to its metabolic functions like protein production, bile production, and drug detoxification. Million people are currently suffering from chronic liver diseases like chronic hepatitis, liver cirrhosis, hepatocellular carcinoma. Due to the limited availability of donors, only a few individuals could receive them.
Therefore, we need to bring forward the tissue engineering approaches aiming to fabricate 3D hepatic tissue in microscale size or whole bioengineered liver synthesis to restore damaged liver function due to a massive injury and resolve the donor shortage problem.
The Liver is the largest organ in the body weighing about 1.5 kg in adults. It is divided into a large right lobe and a smaller left lobe. Each lobe is further divided into lobules. Lobules are the functioning units of the liver. A lobule consists of a row of hepatocytes.
Some important functions played by the liver include:
(a) bile production and secretion.
(b) excretion of bilirubin, cholesterol, hormones, and drugs.
(c) metabolism of fats, proteins, and carbohydrates.
(d) enzyme activation.
(e) storage of glycogen, vitamins, and some minerals.
(f) protein synthesis.
(g) detoxification. Detoxification is a critical liver-specific function.
The loss of liver functions causes life-threatening diseases. Due to the short supply of liver transplants, difficulties with the immunosuppressive drugs, and the possibility of rejection of transplanted tissue, liver tissue engineering basis seems to be the right alternative. dialysis has also been used for short - term survival in patients. Cell encapsulation has been widely used in the case of acute liver failure. this approach gives some time for regeneration of the liver by itself by retrieving some of the liver functions.
Liver Tissue Engineering
These scaffolds bring cells close to each other and enable the formation of cell-cell contacts that mimic cells in the body. As an ideal scaffold degrades at a rate similar to the rate of cell growth and matrix deposition, eventually the synthetic scaffold is completely replaced with natural cells and matrix.
These scaffolds aim to mimic in vivo conditions and facilitate the delivery of nutrients, oxygen, and some other important factors.
Sources of the cell for regeneration
These cells include a primary culture of hepatocytes, ESCs, iPSCs, and MSCs, hPHs, FLC, BM VSEL.
- human Primary hepatocytes (hPHs): They are one of the most mature liver cell sources, as a result, they dedifferentiate in cell cultures. However, researches show that the function and viability of these cells are enhanced when they are in the form of aggregations formation. But there are some, limitations to their use.
- Animal primary hepatocytes: Two kinds of animal primary hepatocytes have been used in liver tissue engineering: 1) rat and 2) porcine hepatocytes. Animal cells are famous for their availability, but they should be used under some special conditions.
- Embryonic stem cells (ESC): they have been an interest in recent studies due to their potential of high proliferation and self - renewing. When injected in mice, they activated tumour formation and ultimately led to cancer. it is a challenge to keep them in an undifferentiated state.
- Induced Pluripotent Stem Cells (iPSC): Differentiated cells such as skin cells can be transformed into an iPSC through reprogramming factors.
- Mesenchymal Stem Cell (MSC): Can be derived from adipose tissue, bone marrow, umbilical cord, amniotic membrane, and many other sources. They stay undifferentiated during the life span until the body needs them.
- Fetal Liver Cells (FLC)
- Human adult liver stem cells/Hepatic liver stem cells (HLSCs)
- Bone Marrow - derived Very Small Embryonic - Like Stem Cells (BM VSEL).
Tissue Engineering Strategy
A major challenge we face in liver tissue engineering is that the liver cells quickly lose their differentiated function. Thus, it is desirable to formulate alternative approaches to more precisely control the organization of cells and vascularization of engineered hepatic tissues.
Hydrogels are desirable as scaffolding materials because of their high water content, biocompatibility, and their mechanical properties, which is similar to those of natural tissues. In general, hydrogels from natural sources can be derived from polymers like collagen, HA, fibrin, alginate, agarose, or chitosan.
As above-mentioned many studies have tried to discover cheap and accessible techniques for the production of definite liver cells or hepatocyte-like cells from different stem cell types. miRNAs influence the process of regeneration of tissues. In a recent experiment, the significance of specific miRNAs has been shown on the differentiation and growth of certain cells.
The use of donor organs is associated with a high chance of primary nonfunction and early graft impairment/rejection as well as a poorer long-term outcome. The only curative treatment suggested for liver disease is transplantation Calling attention, producing decellularized scaffolds from the liver organ.
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About the Author:
Mridula Vats, a graduate student of University School of Chemical Technology, GGSIP University, Delhi. She is pursuing her degree in biochemical engineering and is interested in biotechnology.