Pluripotent Stem Cells as a Treatment for Liver Failure

Pluripotent Stem Cells as a Treatment for Liver Failure

 13 Oct 2021 : 07:00AM

Introduction

Chronic liver disease is a condition where the liver becomes damaged and unable to function properly. It can lead to cirrhosis, cancer, and even death. There are several types of chronic liver diseases, including liver cirrhosis, viral hepatitis, alcoholic liver disease, nonalcoholic fatty liver disease, primary biliary cholangitis, biliary cirrhosis and hepatocellular carcinoma (liver cancer). Acute-on-chronic liver failure ranks globally as the 4th leading cause of death.

Up until now, patients with end-stage liver disease typically had one therapeutic strategy for this condition - liver transplant surgery. Transplantation in patients is considered to be a high-risk procedure and the complications after liver transplantation can seriously affect quality of life. Alternative treatment is an integral part of medical regenerative therapy. 

Regenerative medicine in the form of stem cell-based therapies holds promise as an effective treatment of liver diseases and alternative to liver transplantation. Previous studies and clinical trials using mesenchymal stem cells have already showed some promising results. Pluripotent stem cell therapy is the next frontier as leading cell-based therapy for all forms of liver damage, from acute liver failure to end-stage liver disease. 

What are the types of liver disease?

Liver disease is a condition where the liver does not function properly. It may cause serious problems such as cirrhosis, scarring or cancer.There are many different types of liver disease, viral hepatitis, alcoholic liver disease, nonalcoholic fatty liver disease, primary biliary cholangitis, biliary cirrhosis and hepatocellular carcinoma (liver cancer). Hepatitis is an inflammation of the liver caused by viruses, bacteria, toxins, drugs, alcohol, or autoimmune diseases. Fatty liver disease is a type of liver disease that occurs when fat builds up in the liver.

What causes cirrhosis?

Cirrhosis of the liver is often caused by long term exposure to a toxins. It leads to scarring of the liver tissue and eventually liver failure. Liver cirrhosis patients show end-stage liver disease scores. 

Chronic disease like liver cirrhosis is often coupled with chronic hepatitis, inflammation and autoimmune diseases. The immune cells are often involved in disease progression in acute-on-chronic liver failure patients. Improvement in liver function is always proceeded by positive changes in immune responses. Anti-inflammatory effects and a immunomodulatory therapeutic tool is needed. Pluripotency is indicated. 

What challenges do patients with liver cirrhosis experience? 

Cirrhosis is a condition where the liver becomes damaged and scarred. It causes the liver to become enlarged and hard. The liver is responsible for filtering toxins out of the blood. If the liver does not function properly, these toxins build up in the body and patients experience fatigue, abdominal discomfort and pain. Systemic metabolic problems arise. 

What are Pluripotent Stem Cells?

Pluripotent embryonic stem cells (PESCs) are undifferentiated cells that have the ability to self-renew and repair indefinitely and can therefore be used for regenerative medicine. They release potent paracrine factors that signal repair in all 220+ types of the human body, including hepatic tissue. They release repair transcription factors, like angiocrine factors, that instigate cellular reprogramming of hepatic cells. 

The Case Study

Purpose:

The purpose of this study was to assess the therapeutic efficacy of the Stemaid™ protocol as a cell-based therapy for cirrhosis (alcoholic cirrhosis) and other chronic liver diseases.   Liver function blood tests were taken pre-treatment, during treatment and 18-months post-treatment, in order to assess the beneficial effects of Pluripotent stem cells in the treatment of liver cirrhosis. 

Background:

Acute and long-term therapeutic effects of pluripotent embryonic stem cells (ESC) in patients with liver diseases have been observed at the Stemaid Institute clinical practice since 2012. Pluripotency is comprehensive in its signaling profile and has paracrine effects that are capable of signaling repair in all 220+ tissue types of the body, including liver tissue. Repair of cirrhotic livers and overall liver regeneration is considered possible with the help of pluripotent signaling factors, such as DNA repair factors, growth factors, neurotrophic factors, angiocrine factors and immunomodulatory properties. Cells in liver cirrhosis are considered to be reprogrammable back to their healthy phenotype with pluripotent stem cell treatments. Liver injuries and post-treatment improved liver function can be measured via blood liver profiles in patients with a diseased liver. This case report is of one Stemaid patient with hepatic failure due to chronic liver cirrhosis.

Methods:

The participant aged 62 received 12 intravenous injection treatments of single dose 20 million ESC (Stemaid™ standard line #331) in 50 mL DPBS over a period of 2 weeks. His liver enzymes and bilirubin levels were measured before treatment, one week  into the treatment, on the last day of the treatment and 18 months post-treatment. The patient didn't change his current diet during treatment and kept taking his prescribed medications. He received 5 Ascorbic Acid intravenous infusion therapies during treatment.

Administration route: Intravenous Injections. 

Results:

Day 1 Day 6 Day 12 >18 months Normal Range
AST 166 130 74 55 0-40 U/L
ALT 95 85 51 33 0-38 U/L
ALP 189 196 135 171 33-135 U/L
Bilirubin Total 12.7 8.35 4.02 2.1 0-1.2 mg/dL
Bilirubin Conjugated 8.3 4.09 2.91 0.7 0-0.5 mg/dL
Bilirubin Non Conjugated 4.40 4.26 1.11 1.40 0-0.8 mg/dL
ESR 39 45 40 23 0-15 mm/hr

Discussion:

The patient had a history of heart failure and had a by-pass surgery 8 years prior to the current treatment. His gallbladder was removed 4 years prior to treatment.
The patient had to stop alcohol intake 3 months prior to treatment due to his condition. He wasn't accepted as a candidate for liver transplant due to his history of alcoholism. Icterus, the jaundiced tone of his skin, started to fade at the end of the first week and his energy and appetite improved. The patient reported continuing improvement after returning home and resumed work shortly after, including a flight to Brazil which his doctors initially recommended he cancels. 
Long term function in patient was reported 2 years later. Total bilirubin levels have been at approximately 2.0 mg/dL for 2 years post-treatment.

Conclusion

Stem cell based therapies around the world use many different types of stem cells. The adult stem cell based therapy options are mesenchymal stem cells, hematopoietic stem cells, fat-derived and bone marrow-derived stem cells. Previous studies, clinical trials and systematic review and meta-analysis sources show positive results with adult stem cell-based therapy. However, out of all the cell-based therapies, pluripotent cells have the most wide tissue reach and most potent cellular reprograming potency of all types of cells. Hepatic progenitor cells are quiescent or degenerated in a cirrhotic liver. Exposure to Yamanaka and other pluripotent factors reprograms damaged phenotype to a more healthy youthful state. Daily pulsing dose of pluripotent factors over a period of 2-week and 4-week intervals creates a restorative microenvironment and causes cellular changes towards health. Therapy for Liver disease is vastly accelerated by pluripotent cell type activity and potency. The quality of life of patients with liver diseases improves drastically with these therapeutic effects. 

We hope to see a future pilot study and clinical studies investigating the changes in inflammatory markers and epigenetic markers in the treatment of liver diseases with pluripotent stem cells.







This news item is from Stemaid™ : Pluripotent Stem Cells
https://stemaid.com/news/pluripotent-stem-cells-as-a-treatment-for-liver-failure.html