By:

Louis A. Cona, MD

Reviewed:

Robert J. Hancock

Stem cell therapy for liver disease offers a new hope for the increasing number of patients affected by this condition, which leads to over 33,500 deaths annually in the U.S. This innovative treatment addresses the limitations of past therapies, providing a more accessible and effective option for improving patients' health and quality of life.

Stem cell therapy for liver disease offers a new hope for the increasing number of patients affected by this condition, which leads to over 33,500 deaths annually in the U.S.

This innovative treatment addresses the limitations of past therapies, providing a more accessible and effective option for improving patients' health and quality of life.

Stem Cell Therapy for Liver Disease

Many studies have shown that Mesenchymal stem cells play an essential role in liver recovery, and further research has verified the preliminary effectiveness and safety of these therapies. Stem cell-based therapies will emerge as an effective treatment strategy for liver diseases in 2021 and the future.

According to a recent study published by Li et al. 

At present, it has been preliminarily proved that stem cell therapy for liver failure is effective and safe. However, the long-term efficacy, the regulatory mechanism of stem cell development and differentiation, and the best treatment methods for liver diseases are not clear. (1)

We do know that stem cells have many properties, including immunomodulation, differentiation, and the ability to repair damaged tissues that can be beneficial for liver disease.

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Stem cell Treatment for Liver Cirrhosis

Stem cell treatment for liver cirrhosis is gaining attention for its healing potential, as evidenced by various studies:

• Effectiveness and Safety: A systematic review and meta-analysis found mesenchymal stem cell therapy to be effective and safe for liver cirrhosis. Another meta-analysis supported these findings, showing stem cell transplantation (SCT) can improve clinical outcomes compared to conventional treatment.

• Experimental Studies: Research on mice demonstrated faster liver function recovery with intraportally introduced cellular technologies, as noted here.

• Influencing Factors: The effectiveness of stem cell therapy can be affected by other factors, such as steroids reducing the efficacy of mesenchymal stem cell therapy, as discussed in this study.

• Clinical Impact: A study in Bangladesh found a dominant effect on ascites in liver cirrhosis patients post-therapy, although biochemical parameters remained largely unchanged. The number of patients with ascites decreased significantly after treatment, as detailed here.

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Is Stem Cell Therapy a Cure for Liver Cirrhosis?

Stem cell therapy is not a cure for liver cirrhosis but is being investigated as a potential treatment for liver cirrhosis. Key points include:

• Current Status: Research is in early stages, with more comprehensive studies needed to confirm safety and efficacy, as suggested in this study.

• Potential Benefits: A systematic review and meta-analysis indicates mesenchymal stem cell therapy could slow fibrosis progression and enhance life expectancy in hepatic cirrhosis, but further research is essential.

• Clinical Findings: A study in Bangladesh showed stem cell therapy's significant impact on ascites, a liver cirrhosis complication, but no major changes in biochemical parameters, highlighting its symptom management potential without reversing the disease, as noted here.

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Stem cell therapy offers promise in treating liver cirrhosis but requires more research to be considered a cure, particularly regarding its long-term efficacy and safety.

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Current liver disease treatments are plagued with issues

Liver disease has had an increasing incidence and has become a troubling cause of death in more people each year. It accounts for over 33,500 deaths in the U.S. alone every year. Unfortunately, past treatments for damaged or diseased livers have been plagued with issues.

Treatments are often rarely available, too expensive, or come with large costs of quality of life for patients. However, advances in stem cell treatments have created a new path toward regaining their health for patients with liver disease.

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Can stem cell therapy treat liver cirrhosis?

Cirrhosis of the liver is characterized by internal scarring and subsequent dysfunction of the liver. Liver cirrhosis can be caused by many different factors, but most notable is due to alcohol consumption, viral hepatitis B or C, and metabolic disorders.

"Although certain parts of the liver can naturally regenerate, the only proven treatment for end-stage liver disease is a full liver transplant."

Unfortunately, a liver transplant is extremely expensive, donors are hard to come by, and there is a risk of rejection of the organ by the patient's body.  

Mesenchymal stem cell therapy may be used as an alternative treatment option. Mesenchymal stem cells (MSCs) can restore liver injury after differentiation (changing into new types of useful liver cells) and exert immunomodulatory, anti‐inflammatory, antifibrotic, antioxidative stress all potentially leading to organ function improvements. (4)

Differentiation (becoming new types of cells)

Stem cells have the unique ability to morph or differentiate into different types of cells within the body. In this way, stem cells can be used to seek out damaged liver tissue and regenerate the organ itself. 

Mesenchymal stem cells are multipotent stem cells that can self-renew and differentiate into different cell types. In other words, mesenchymal stem cells can become a variety of different cell types including; adipose tissue, cartilage, muscle, tendon/ligament, bone, neurons, and hepatocytes (2)

According to a 2016 study conducted by Almalki et al. - "The differentiation of MSCs into specific mature cell types is controlled by various cytokines, growth factors, extracellular matrix molecules, and transcription factors (TFs). (2)

Mesenchymal stem cells contribute to tissue regeneration and differentiation, including the maintenance of homeostasis and function, adaptation to altered metabolic or environmental requirements, and the repair of damaged tissue. (3)

Anti-inflammatory properties of mesenchymal stem cells (MSCs)

Mesenchymal stem cells significantly reduce inflammatory factor secretion, immune cell infiltration, and hepatocyte apoptosis (liver cell death) and up‐regulate levels of antioxidants and energy metabolism in acute liver injuries. (4)

According to a study conducted by Hu et al. "At the cellular level, inflammatory signals promote the proliferation of MSCs and mesenchymal‐to‐epithelial transformation, suppress HSC differentiation into fibrogenic myofibroblasts and encourage immune cells to adopt an anti‐inflammatory phenotype. (4)

Stem cell liver disease study shows positive results

Although available data is limited and tests are still ongoing, a study ran by PubMed in 2013 used 11 clinical trials to test the use of stem cells on damaged liver patients. The independent trials showed that not only were stem cells a safe form of intravenous treatment for liver failure, but all of the trials reported positive results. 

The results ranged from improvements to quality of life and quantitatively improving liver function, to reducing morbidity and mortality. The studies showed patients to have a significant decrease in the MELD score (The Model for End-Stage Liver Disease), MELD score measures the risk of mortality in patients with liver disease. 

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Stem Cells for Autoimmune Hepatitis (AIH)

Stem cell therapy is emerging as a promising treatment for autoimmune hepatitis (AIH), a severe liver disease, with various studies highlighting its potential:

• MSCs-Derived Exosomes: These have been explored as drug carriers. A study found that dexamethasone-incorporated exosomes improved dexamethasone accumulation in the liver, indicating potential for AIH treatment, as detailed here.

• Menstrual Blood-Derived Stem Cells: Human menstrual blood-derived stem cells (MenSCs) significantly decreased mortality and improved liver function in an AIH mouse model, as shown in this research. The effect was linked to apoptosis regulation and signaling pathway modulation.

• Stem Cells from Human Exfoliated Deciduous Teeth: These cells protected hepatocytes from apoptosis and alleviated acute liver injury in AIH models, suggesting another potential therapy approach, as found in this study.

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These findings suggest that various forms of stem cell therapy could be effective strategies for treating AIH.

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Stem Cell Therapy for Hepatic Insufficiency

Stem cell therapy is being investigated as a treatment for hepatic insufficiency, offering an alternative to liver transplantation. Key aspects include:

• Mesenchymal Stem Cells (MSCs): MSCs are notable for their multipotent nature and therapeutic effects like anti-fibrosis and hepatocyte proliferation, as detailed in this study.

• Types of Stem Cells: There are embryonic stem cells (ESCs) and adult stem cells (ASCs), which include hematopoietic stem cells (HSCs) and MSCs. While ESCs have high potential, ethical and safety concerns limit their use.

• Application in Liver Damage: Stem cell therapy has shown improvement in hepatic injury in viral infection models, with potential in treating hepatic fibrosis, as discussed here.

• Challenges: A key challenge is monitoring treatment effectiveness, with further research needed to understand stem cell therapy mechanisms for hepatic insufficiency and to develop effective monitoring systems.

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Although promising, the full potential and mechanisms of stem cell therapy in hepatic insufficiency require more comprehensive research and effective monitoring solutions.

What does the future look like?

Liver disease is difficult to treat, but stem cell treatments have provided a bright future for patients. While the positive results of treatment are continuing to be reported, some patients find the lack of a required transplant reason enough to seek potential treatment. 

There have already been numerous success stories for patient recovery without the need for transplant. With transplant costs reaching over $150,000 for the first year after treatment, stem cells are providing patients with an affordable and sustainable way forward.  

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References: 

(1) Li, S., Bi, Y., Duan, Z., Chang, Y., Hong, F., & Chen, Y. (2021, May 15). Stem cell transplantation for treating liver diseases: progress and remaining challenges. American journal of translational research. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205777/.

(2) Almalki, S. G., & Agrawal, D. K. (2016). Key transcription factors in the differentiation of mesenchymal stem cells. Differentiation; research in biological diversity. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5010472/.

(3) Grafe, I., Alexander, S., Peterson, J. R., Snider, T. N., Levi, B., Lee, B., & Mishina, Y. (2018, May 1). TGF-β Family Signaling in Mesenchymal Differentiation. Cold Spring Harbor perspectives in biology. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5932590/.

(4) Hu, C., Wu, Z., & Li, L. (2020, January). Pre-treatments enhance the therapeutic effects of mesenchymal stem cells in liver diseases. Journal of cellular and molecular medicine. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6933358/.