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Liver Development and Regeneration - An Overview

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This article comprises information about liver function, regeneration, and development. Read the article below to know more about them.

Medically reviewed by

Dr. Jagdish Singh

Published At November 2, 2022
Reviewed AtApril 18, 2023

Introduction:

The liver is the unique and largest vital organ of the human body. It is located on the upper right side of the abdomen beneath the diaphragm. The liver is divided into two lobes; it is cone-shaped and is a dark brown-reddish organ that weighs around three pounds. The liver's main function is to metabolize the drugs and detoxify the body, and it also secretes bile that helps carry waste products from the liver.

What Are the Functions of the Liver?

The liver carries out many endocrines as well as exocrine functions. Some are:

  • Bile production helps to carry waste products.

  • Breaking down fats in the small intestine.

  • It produces proteins from blood plasma.

  • Conversion of excess glucose into glycogen.

  • Liver stores iron, processing hemoglobin for use.

  • The metabolization of drugs and medications.

  • Regulates blood clotting.

  • Production of serum proteins.

  • Glycogen storage.

Most liver functions are carried out by hepatocytes, the liver parenchymal cells, which are highly polarized cells and form cords.

How Does Liver Development Occur?

  • The liver is the largest vital organ in the human body that performs endocrine and exocrine functions.

  • Hepatocytes are the main cells in the liver; about 80% of the mass of the organ is hepatocytes.

  • Along with the hepatocytes, cholangiocytes, that is, biliary epithelial cells that are derived from embryonic endoderm, are present.

  • Cells of mesoderm origin are stromal cells, Kupffer cells, stellar cells, and blood vessels.

  • Liver development occurs through the process of hepatogenesis.

What Happens In the Embryonic Stage of Liver Development?

The totipotent stem cells of blastocyst differentiate into multipotent tissue-specific progenitor cells. Along with the foregut closure, the medial and lateral domain fuse and endodermal cells lead to hepatic fate under genetic factors and indicative signals.

What Are the Steps of Liver Development?

The steps of liver development are:

  • Liver tissue and development derive from the endoderm layer, and its organogenesis is conserved among vertebrate species.

  • Endoderm is the monolayer of cells that form tubes in the foregut, midgut, and hindgut; liver diverticula appear on the ventral surface of the foregut adjacent to the cardiac mesoderm.

  • This diverticula transitions from monolayer cells to a multilayer of pseudostratified cells called hepatoblasts.

  • These hepatoblasts proliferate and move to the surrounding septum transversum to form a bud, a liver bud.

  • Hepatocytes and cholangiocytes initiate differentiation from hepatoblasts. Based on multiple signaling pathways, hepatic development occurs.

  • Signaling programs and gene transcription programs with Wnt (wingless signaling pathway), Notch, transforming growth factors, morphogenic protein, and all interactions between cells enable liver development.

What Is Liver Regeneration?

The regrowth of liver tissue as a reaction to any kind of infection is known as the regeneration of the liver. Out of all organs in the human body, the liver has a high capacity for regeneration. Liver regeneration is divided into three phases: primary phase, proliferative phase, and termination phase.

What Happens in Different Phases of Liver Regeneration?

Liver regeneration is mainly into three parts:

  • Primary Phase: Inflammation of the liver in diseased conditions targets the inflammatory cells to release cytokines and growth factors that are induced by primary inflammation. Kupffer cells produce cytokines and immunomodulating factors. The widely known main cytokines are TNF-alpha and IL-6, which inhibits the effect of hepatic inflammation and injury.

  • Proliferative Phase: This is the second phase and is subdivided into two, mitogens and auxiliary mitogens. Mitogens proliferate hepatocyte proliferation, while the auxiliary mitogens proliferate bile acids, epinephrine, insulin growth factor, endothelial growth factor, and serotonin. Though they are not mitogenic, their absence can delay the liver regeneration process.

  • Termination Phase: In this phase, the proliferation and regeneration stop and normal liver mass and function are maintained. For this, anti-proliferative factors are responsible; the most commonly known are TGF-beta and its TGF-beta family members.

How Does Liver Regeneration Help in Curing Other Liver Diseases?

Regenerative medicine is a great developing field that helps the patient during the waiting period before the whole liver transplant and when there is no availability of the liver for transplantation surgery.

The therapies that are provided are:

  • Living Donor Transplants: In this procedure, a part of the healthy donor's liver is removed to replace the patient's diseased liver. The liver’s regenerative ability regenerates the donor's healthy liver as well as the recipient's. Both the liver regenerates and grows back to normal size.

  • Extracellular Vesicle-based Therapies: In this procedure, the stem cells are brought together in manufacturing to its clinical stage; it is a therapeutic therapy for various liver injuries and diseases.

  • Liver Assist Devices: Many types of artificial devices are available now - bioartificial livers; these devices perform functions of the liver till the patient receives the donor’s liver by liver transplantation. These devices contain pig liver (hepatocytes) cells and spheroids that compensate for the liver functions of patients.

  • Patient-specific Liver Cell Transplantation: In this procedure, cells from the patient's body are taken, and gene therapy is used on them to correct the genetic defect. The treated cells are again transplanted into the patient's body; in this way, no immunosuppressive drugs are required.

What Are the Factors Affecting Regeneration After a Liver Transplant?

Most of the complications and factors affect the regeneration process when the transplantation of the liver is cadaveric, that is, the donor is dead. In this situation, there is a huge loss of hepatocytes in the organ; this occurs due to:

  • Alloimmune Response: Immunity that produces an immune response against antigens from the same cells and species.

  • Ischemia-Reperfusion Injury: Injury caused by the blood which returns to the tissue after the damage to the tissue occurs, especially after hypoxia (lack of oxygen).

  • Others: Damage that may have affected the liver.

Conclusion:

The liver has always been a matter of interest for researchers for its developmental and regenerative properties. Regenerative medicine is a promising technology for the treatment of liver and severe hepatic conditions. Future research is going on to create a whole bioengineered liver. However, in severe infections and injuries, the regenerative capacity of the hepatocytes in the liver decreases and fades out, leading to life-threatening conditions. Identification research and details about development and regeneration, the role of stem cells, and underlying molecular mechanisms have opened doors for many therapeutic therapies and future treatment procedures for chronic fatal liver conditions.

Frequently Asked Questions

1.

What Are the Steps Involved in Liver Regeneration?

Regeneration of the liver is constant among vertebrates and is derived from the endoderm. The foregut, midgut, and hindgut are formed from a monolayer of endodermal cells. The liver diverticula is seen in the ventral surface of the foregut. Hepatoblasts are a layer of pseudostratified cells that replace the monolayer that makes up the diverticula. They multiply and travel to the surrounding transverse septum to form a liver bud. Hepatocytes and cholangiocytes start differentiation from hepatoblasts.

2.

Is It True That The Liver Regenerate Every Three Years?

The liver can recover from damage every day. However, severe damage might take three months to a year to fully repair. This unique ability to regenerate helps the liver to maintain an age of less than three years throughout a person’s life. On the contrary, it does not heal the scars of liver cirrhosis (severe scarring of the liver).

3.

When Does the Liver Begin to Develop?

The liver begins to develop at three weeks of gestation. Gestation is the period when a fetus matures within the womb of the mother. The liver grows rapidly from the fifth to the tenth week. 

4.

Can A Liver Regenerate Completely?

The liver can regenerate almost completely. It can repair its damage up to ninety percent, even if most of it is removed.  However, many diseases may cause damage to the liver, which can be beyond repair.

5.

What Are the Food That Promote Liver Regeneration?

Berries, cruciferous vegetables, beans, whole grains, nuts, and fatty fish are some of the foods that promote liver regeneration. Coffee and tea contain antioxidants that promote liver regeneration. Apples, grapes, and citrus fruits like orange and lemon are considered friends of the liver as they boost liver health. 

6.

What Symptoms Indicate a Sick Liver?

A general feeling of unwellness and tiredness is the first sign of any sickness. Yellowing of the skin and whiteness of the eyes is a condition called jaundice; the next sign is seen. Fluid retention in the feet and ankles (pedal edema) is another sign of a weak liver or a liver not functioning properly.

7.

Can the Liver Recover After Cirrhosis?

Cirrhosis of the liver causes scarring, which in most cases is irreversible. Scarring of the liver is not reversible. However, stopping alcohol can prevent further damage to the liver. 

8.

Does Fatty Liver Harm the Liver?

Fatty liver may not damage the liver permanently during the early stages. But it can cause inflammation of the liver. If it continues, it can cause serious damage to the liver.

9.

How Can My Liver Be Naturally Healed?

The liver can be healed by following a healthy diet and lifestyle. Including a lot of fiber in food can promote liver health. Stopping or limiting alcohol can help prevent further damage to the organs. Plenty of exercise and hydration boost liver health. 
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Dr. Jagdish Singh
Dr. Jagdish Singh

Medical Gastroenterology

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liver development and regeneration
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