Liver Regeneration with Stem Cells: A Potential Cure for Hepatitis & Cirrhosis

Did you know the only organ that can regenerate is Liver, as it can regenerate on its own to a full size even after 90% of it is removed or damaged.

Despite the liver having the best regenerative capacity why the need for transplant or stem cells therapies arises? The answer to this is, sometimes several diseases and conditions damage the liver to an extent to which it is impossible for the liver to undergo self-regeneration and repair itself. Thus, for regeneration of liver, requirement for transplant and other therapies arises.

Around 800 million people worldwide live with chronic liver diseases. And of all the annual deaths that occur due to diseases, liver diseases constitute about 3.5% of all the deaths i.e. 2 million deaths. Moreover, there are 4 stages of progression in liver diseases. They are inflammation, fibrosis of the liver leading to cirrhosis and eventually leading to end stage liver disease.

Defining liver diseases

Liver disease is posing a serious challenge globally and the disadvantage of existing conventional treatment is that it does not focus on liver regeneration and rather focuses on either just managing the condition by treating the symptoms or taking the extremely difficult route towards transplantation.

The kinds of liver diseases that we see commonly in patients are:

1. Liver fibrosis: fibrosis begins with injury, trauma or any inflammation that occurs in the liver and leads to accumulation of scar tissue. 
2. Liver cirrhosis: if the liver continues to be in the state of fibrosis, it transforms into cirrhosis. Therefore, cirrhosis is progression of tissue scarring which further impairs functions of the liver. 
3. Hepatic carcinoma: as the name suggests, cancer of the hepatic cells determines hepatic carcinoma.

The causes of liver fibrosis, cirrhosis and hepatic carcinoma are 

1) Hepatitis: a condition where hepatitis virus causes liver inflammation and alters liver functions. 

2) Alcoholic hepatitis: similarly, it is condition which damages liver and inflammation of liver occurs due to too much consumption of alcohol and lastly,

3) Autoimmune hepatitis: a condition where the immune system loses its track and attack person’s own hepatic cells leading to damage of the hepatocytes.

Can stem cells cure liver disease?

Stem cells therapy is proving its potential time and again with its ability to regenerate into specialized type of cells depending on the condition and disease. This time around in liver diseases also stem cells regenerate into hepatocytes, the primary cells of liver and exert anti-inflammatory and anti-fibrotic effects.

1. In conditions like cirrhosis and liver failure, stem cells differentiate into hepatic cells and promote regeneration. The restoration of hepatic cells restores functions of the liver.
2. The main cause of liver damage is fibrosis, but stem cells have the potential to reduce the formation of tissue scar which in turn slows the progression of fibrosis into cirrhosis.

The beauty of stem cells therapy is personalized treatment approach. It gives an option to carry out personalization of the therapy depending upon the patient’s genetic makeup, characteristic features and condition.

Mechanisms of stem cell therapy for liver regeneration

There are several mechanisms for regenerating liver with stem cells that range from proliferation, differentiation to anti-fibrosis, anti-inflammation and immunomodulation.

MSC’s Immunomodulation effect

MSC secrete certain bioactive molecules and factors in chronic liver diseases to exert immunomodulation mechanism which mitigates inflammation. MSC stimulate the release of PGE2, IL-10, IL-11, TGF-β, and hepatocyte growth factor (HGF). Additionally, they also inhibit Th-1 and Th-17 cells by inducing Treg cells. Therefore, the net result of all these secretions is reduction of inflammation leading to delay in progression of disease and regeneration of liver.

Proliferation and Differentiation function

The main property of MSC is to differentiate and proliferate into hepatocyte-like cell and promote angiogenesis. Hence, because of this ability it can replace the cells that the liver damages and restore normal liver function.

Mechanism of Anti-fibrosis

MSCs inhibit the activation of hepatic stellate cells which slows down the process of fibrosis, since; hepatic stellate cells produce certain components which lead to fibrosis. Similarly, stem cells secrete an enzyme metalloproteinase, which degrade the components that hepatic stellate cells produce which resolute existing fibrosis. Furthermore, MSCs also have the ability to reduce fibrosis by initiating apoptosis of hepatic stellate cells. Thus, these mechanisms prevent the progression of liver disease from fibrosis stage to cirrhosis and stimulate liver regeneration.

Observations from studies post stem cells infusion

1. The study “Transplantation with autologous bone marrow-derived MSC for alcoholic cirrhosis” reports that MSC improves both the fibrosis stage and child-Pugh score and initiate regeneration of liver and there were no adverse effects.
2. In a randomized control trial for chronic liver failure induced by hepatitis B virus using Allogeneic bone marrow-derived mesenchymal stromal cells, there was enhancement of liver function. Additionally, the study also suggests that there was a better control of infection and fatality in those patients.
3. And another randomized control trial using MSC therapy in decompensated liver cirrhosis reports improvement in both liver function as well as patient survival and there was no reports of tumours and adverse effects in the trial.

What makes MSC the go to therapy for liver regeneration in chronic liver diseases?

The following constitutes the reasons why healthcare providers lean towards MSC therapy for liver regeneration.

1. MSC can easily differentiate into hepatocytes due to its regeneration and differentiation capacity.
2. The ability of MSC to reduce inflammation and regulate immune system by exerting immunomodulation.
3. MSC stimulate apoptosis of hepatic stellate cells (HSCs) by releasing TNF and IL-10.
4. They also play an important role in protecting the liver by inhibiting the process of hepatocyte ferroptosis.

The above are some of the functions of liver regeneration that make MSC therapy a preferable choice.

Liver Patient Success Stories

Why does stem cells therapy have an edge over transplantation in liver regeneration in chronic liver diseases?

The current existing conventional treatment options for severe liver damage or liver failure ranges from medications for treating symptoms and managing the condition to transplantation of liver. 

1. Firstly, the absence of sufficient number of donors for transplantation.
2. Then, transplantation is only successful if there is no graft rejection.
3. Need to take medications for a long period of time.
4. The regeneration potential of stem cells therapy and repair of the damaged tissue.
5. And finally, MSC has numerous properties like anti-inflammatory, anti-fibrotic and anti-apoptic.

Therefore, above are the rationales that suggest paradigm shift towards stem cell therapy for regeneration of liver.

Summary/ key takeaways

The following are the concluding points regarding stem cell therapy for liver damage. For the treatment of chronic liver diseases, stem cell therapy is currently studied as a potential solution for liver regeneration. 

Since, chronic liver diseases damage liver to an extent where regeneration of liver is not possible, it is necessary that we employ strategies which can stimulate the process of regeneration of damaged tissue. And fortunately, MSC stimulate liver regeneration, and the liver exhibits various functions and has a remarkable ability to regenerate. This characteristic makes stem cell therapy a promising option for treating chronic liver diseases. However, further research is needed to determine the long-term outcomes and to address the existing challenges related to liver regeneration.

Hence, the above are the concluding remarks about blog for liver regeneration with stem cells.

FAQs

Q: What is the difference between fibrosis and cirrhosis?

Fibrosis begins with injury, trauma or any inflammation that occurs in the liver and leads to accumulation of scar tissue. On the other hand, if the liver continues to be in the state of fibrosis, it transforms into cirrhosis. Cirrhosis is progression of tissue scarring which further impairs functions of the liver.

Q: How do stem cells cure liver diseases?

Stem cells regenerate due to its ability into specialized types of cells i.e. hepatocytes. Hepatocytes, the primary cells of the liver, cure liver diseases by exerting anti-inflammatory and anti-fibrotic effects.

Q: What is autoimmune hepatitis?

As the name suggests, autoimmune hepatitis is a condition where the immune system attacks a person’s own hepatic cells leading to damage of the hepatocytes.

Q: How does MSC exhibit anti-fibrotic effect?

MSCs inhibit the activation of hepatic stellate cells which slows down the process of fibrosis, since; hepatic stellate cells produce certain components which lead to fibrosis. Similarly, stem cells secrete an enzyme metalloproteinase, which degrade the components that hepatic stellate cells produce which resolute existing fibrosis. Additionally, MSCs also can reduce fibrosis by initiating apoptosis of hepatic stellate cells. Thus, these mechanisms prevent the progression of liver disease from fibrosis stage to cirrhosis.