Key Takeaways & Executive Findings
- ā¢ā¢ MSCs are the most extensively studied stem cell type for ESLD, with 25 preclinical and clinical studies reviewed. ā¢ Core mechanisms include differentiation into hepatocyte-like cells, immunomodulation, and inhibition of fibrosis. ā¢ Clinical translation faces challenges such as donor shortages, immune rejection, and high costs, but novel opportunities are emerging. ā¢ MSC therapy offers a promising alternative to liver transplantation by delaying or reversing liver fibrosis or failure.
Abstract
End-stage liver disease (ESLD) is one of the predominant diseases contributing to high morbidity and mortality worldwide, with etiologies including alcoholic liver disease, viral hepatitis, non-alcoholic fatty liver disease, and metabolic-associated liver disease. Currently, liver transplantation remains the only effective treatment, however, its clinical application is significantly limited by donor shortages, immune rejection, and high medical costs. Among the five types of stem cells that have been experimentally applied to liver diseases, mesenchymal stem cells (MSCs) have emerged as the most extensively studied, with the largest number of experimental and clinical research platforms worldwide. This review compiles findings from 25 preclinical and clinical studies on MSCs in the treatment of ESLD, aiming to elucidate the core mechanisms of action and then outline both the challenges in MSC clinical translation and the novel opportunities arising from cutting-edge research.
1. Introduction
As the largest solid organ in the human body (approximately 1.4 kg), the liver maintains systemic homeostasis through its dual blood supply system and three core functionsānutrient regulation, toxin neutralization, and metabolic coordination. Its unique capacity to balance detoxification and metabolism is crucial for overall health. However, the global prevalence of liver diseasesāsuch as alcoholic liver disease, viral hepatitis, and a marked rise in conditions linked to overweight and obesity, including non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and metabolic-associated liver diseaseācan ultimately progress to end-stage conditions such as cirrhosis and liver failure [1].
End-stage liver disease (ESLD) represents a global health crisis, with the number of affected individuals continuing to rise at an alarming rate each year [2ā4]. While liver transplantation remains the only curative treatment, its clinical application is severely limited by donor shortages, immune rejection, and high costs [5, 6]. This therapeutic gap has driven the exploration of alternative treatments, among which stem cell-based therapies have demonstrated breakthrough potential.
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Shiqi Li, Yichen Wang, Su-meng Li, Yaxin Zhu, Yan-qin Du, Xin Zheng, Jun Wu (2026). Mesenchymal stem cell therapy for end-stage liver disease: adversity and opportunity. Stem Cell Research & Therapy. https://doi.org/10.1186/s13287-025-04788-3
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Frequently Asked Questions
What is end-stage liver disease (ESLD)?
ESLD is a terminal stage of chronic liver disease characterized by cirrhosis or liver failure, often caused by alcoholic liver disease, viral hepatitis, non-alcoholic fatty liver disease, or metabolic-associated liver disease.
Why is liver transplantation not always feasible for ESLD?
Liver transplantation is limited by donor shortages, immune rejection risks, and high medical costs, making it inaccessible for many patients.
How do mesenchymal stem cells (MSCs) help in treating ESLD?
MSCs can differentiate into hepatocyte-like cells, modulate immune responses, and inhibit fibrosis, thereby promoting tissue regeneration and functional recovery in the liver.
What are the main challenges in translating MSC therapy to clinical practice?
Challenges include ensuring consistent cell quality, avoiding tumorigenicity, managing immune compatibility, and overcoming regulatory and cost barriers.
What novel opportunities are emerging in MSC therapy for ESLD?
Cutting-edge research is exploring gene editing, biomaterial scaffolds, and combination therapies to enhance MSC efficacy and safety, offering new hope for ESLD patients.
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