HepaStem consists of liver-derived Mesenchymal Stem Cells that are obtained from ethically healthy donated organs and expanded in the lab.

Learn in the 3D animation below about the multiple modes of action of HepaStem and why the technology is ideal to promote immune modulation and reduce tissue fibrosis for devastating immune-mediated liver diseases.


Chronic liver injury is caused by multiple hits, such as viral infection, toxic injury or excessive calory intake. NASH, is due to mainly fat accumulation leading to systemic liver inflammation, progressive fibrosis and eventually end-stage liver disease.


In additional, patients with chronic liver disease are at risk of abrupt loss of liver function, called ACLF.

Liver injury starts with hepatocyte damage triggering the process of programmed cell death. This is followed by activation of hepatic stellate cells, increased deposition of collagens together with inflammatory cell infiltration , activation and the release of pro-inflammatory cytokines.

HepaStem, administered intravenously, circulates in the body and enters the liver via the bloodstream. After reaching the liver, HepaStem has multiple modes of action and targets several altered pathways. The cells will cool down the pro-inflammatory environment, inhibit hepatic stellate cells activation and collagen secretion.

The combination of the immunomodulatory and anti-fibrotic potential builds on the tissue repair support function.

Therefore, Promethera believes that its HepaStem technology is ideal to promote immune modulation and reduce tissue fibrosis for devastating immune-mediated liver diseases

Acute-on-chronic liver failure (ACLF)

ACLF is a recently recognized syndrome characterized by acute decompensation of cirrhosis associated with organ/system failure(s) (liver, kidney, brain, coagulation, circulation and/or lung) and poor survival. (27)

Common precipitants of acute decompensation of liver function include bacterial and viral infections, alcoholic hepatitis, and surgery, but in more than 40 % of patients, no precipitating event is identified.

Epidemiological studies indicate that there is an increasing prevalence of liver cirrhosis related to chronic infection by hepatitis C or B virus, alcohol consumption and non-alcoholic steatohepatitis worldwide (28). The natural course of cirrhosis is from compensated to decompensated disease. Decompensation is characterized by the development of complications related to portal hypertension and liver failure (variceal bleeding, ascites, hepatic encephalopathy and bacterial infections) and is associated with poor prognosis.

Approximately 31% of patients admitted to a hospital for acute decompensation of cirrhosis have ACLF at admission (20%) or develop the syndrome during hospitalization (11%). 

It is estimated that the incidence of ACLF patients in Europe (EMA), the U.S. and Japan is more than 70,000 patients annually.


27. Bernal, W. et al. Acute-on-chronic liver failure. Lancet 386, 1576-1587, doi:10.1016/S0140-6736(15)00309-8 (2015).

28. Murray, C. J. et al. GBD 2010: a multi-investigator collaboration for global comparative descriptive epidemiology. Lancet 380, 2055-2058, doi:10.1016/S0140-6736(12)62134-5 S0140-6736(12)62134-5 [pii] (2012)

Nonalcoholic Steatohepatitis (NASH)

Nonalcoholic fatty liver disease (“NAFLD”) is one of the world’s most significant liver-related health problems. Being overweight or obese is a primary risk factor for NAFLD, with 80% of obese people and a high proportion of diabetics (40-70%) estimated to have NAFLD.  The severity of the disease is assessed histologically using the NAFLD Activity Score (“NAS”), which consists of the unweighted sum of scores of steatosis, hepatocyte ballooning, and lobular inflammation.

Nonalcoholic steatohepatitis (“NASH”) is defined as a sub-form of NAFLD when the simultaneous presence of any degree of steatosis, lobular inflammation, and ballooning of the liver can be observed as a result of liver inflammation and damage caused by a build-up of fat in the liver.  In simple steatosis, fat accumulates in the liver with no presence of significant inflammation or liver fibrosis, whereas in NASH, liver steatosis is associated with hepatic inflammation, hepatocellular ballooning, and fibrosis, which can render it indistinguishable from alcoholic steatohepatitis.  As NASH is the progressive form of liver disease, it carries the risk of progressive fibrosis, cirrhosis, and end-stage liver disease, and is primarily characterized by hepatic necro-inflammation.  NASH is a slow developing condition and, as a result, the intensity of a patient suffering from NASH can vary and NASH therefore often goes undiagnosed in the larger population.

The prevalence of NAFLD is increasing worldwide in parallel with the obesity epidemic. It is estimated that the prevalence of NAFLD in the adult US population is 30%-40%, while studies from other parts of the world report a prevalence ranging from 6% to 35% (median approximately 20%)[6]. Furthermore, it has been estimated that 15%-20% of patients with NAFLD have NASH. This translates into a NASH prevalence in the general population of 3%-5%. A more recent study from the US observed an even higher prevalence of NAFLD and NASH in the general population (46% and 12%, respectively), and 2.7% in the entire cohort had established, advanced NASH related liver fibrosis, leading to an estimated > 2 million US adults with NASH related, advanced liver disease[8]


6. Miyajima, A., Tanaka, M. & Itoh, T. Stem/Progenitor Cells in Liver Development, Homeostasis, Regeneration, and Reprogramming. Cell Stem Cell 14, 561-574, doi:10.1016/j.stem.2014.04.010 (2014).

8. HEPAMAP. A roadmap for hepatology research in Europe: An overview for policy makers.  (2016).