Stem program: cell therapy will protect against liver fibrosis

Russian scientists have studied the long-term effects of cell therapy in liver fibrosis. In an animal experiment, they compared the effectiveness of mesenchymal stromal cells (MSCs) derived from adipose tissue and bone marrow. Both approaches have provided positive dynamics in the long term. The next stage will be the improvement of cell transplantation technologies for the correction and treatment of acute and chronic liver failure. At the same time, cell therapy has not yet been officially recognized as the standard of medical care, experts noted. Such procedures can only be carried out within the framework of scientific research.

Cellular therapy of liver fibrosis

Scientists from Sechenov University, together with colleagues from the V.I. Shumakov National Research Medical Center for Transplantation and Artificial Organs and the Bauman Moscow State Technical University, modeled liver fibrosis in rats, after which MSCs from bone marrow or adipose tissue were injected into the animals. The liver condition was assessed after 14, 30, 90, and 270 days. The scientists analyzed the biochemical parameters of the blood, the condition of the organ tissue and signs of its regeneration.

The differences between the two cell therapy options persisted for a long time. Nine months after the introduction of cells, the histological picture was more favorable in animals that received MSCs from adipose tissue than in the bone marrow MSCs group: in particular, the area of reticular fibers and the number of cells with the Ki67 proliferation marker differed. According to the authors, this indicates a higher potential of MSCs of adipose tissue for long-term liver tissue repair.

— There are very few studies comparing the effect of mesenchymal stromal cells from adipose tissue and bone marrow in liver fibrosis, and there are practically no studies with a long follow-up period. Therefore, it was important for us to evaluate the possibilities of both approaches and share our accumulated experience in using cellular technologies. So far, this area is at an experimental stage, but the existing regulatory framework allows us to consider the prospects for its implementation in clinical practice," said Murat Shagidulin, MD, Professor at the Department of Transplantation and Artificial Organs at the N.V. Sklifosovsky Institute of Clinical Medicine at Sechenov University.

The results obtained expand the understanding of the long-term effect of cell therapy in liver fibrosis and will help to more accurately select the source of MSCs for further research. The authors note that in order to move to clinical use, it is necessary to continue studying the safety, mechanisms of action and stability of the therapeutic effect.

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""Unlike the outdated idea that MSCs simply transform into new hepatocytes (liver cells), their main therapeutic effect is now associated with the paracrine effect," Dmitry Konstantinov, head of the Department and Clinic of Infectious Diseases with Epidemiology, infectious diseases specialist (hepatologist), expert at NTI "Helsnet", told Izvestia. The cells do not so much repair the organ directly, as they change the microenvironment in the liver.

— Autologous (proprietary) or allogeneic (donor) cells are used for clinical use. The most available sources are bone marrow, umbilical cord blood cells, and fat cells. They can be delivered to the body in several ways: intravenous infusion (the most common method that allows cells to linger in the capillaries of the lungs and liver), injection through the portal vein, selective delivery to the hepatic artery, or direct injection directly into the liver tissue under ultrasound control," the expert said.

Currently, the treatment of liver fibrosis with MSCs is at the stage of active clinical trials all over the world, including Russia, Dmitry Konstantinov noted. Experiments on animal models have convincingly demonstrated the ability of MSCs to slow down and partially reverse scar formation.

— If we talk about cirrhosis and severe fibrosis at the stage before decompensation, cell therapy can really slow down the pathological process and create conditions for the restoration of one's own liver tissue. However, with irreversible cirrhosis with a rebuilt vascular network, MSCs are more likely to be able to stabilize the condition and maintain organ function, but not eliminate the need for transplantation," said Evgenia Krylova, gastroenterologist and acting director of the NSU Medical Center.

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Today, this is an experimental field," said Alexey Nikitin, MD, cardiologist at "Invitro". Fibrosis is reversible, and this has been proven without any cell therapy: after hepatitis C eradication, hepatitis B suppression, alcohol withdrawal, or weight loss in metabolically associated fatty liver disease, the severity of fibrosis decreases in a significant proportion of patients.

— Cirrhosis is already a restructuring of the architecture of an organ with regeneration nodes and vascular shunts; at this stage, the reverse development is only partially possible and not at all, — said the specialist.

Despite the abundance of "stem therapy" offers in private clinics, the treatment of liver fibrosis with mesenchymal cells is not officially recognized as the standard of medical care. The procedure should be carried out strictly within the framework of certified clinical protocols and scientific research, the experts emphasized.

The results of the study are published in the International Journal of Molecular Sciences.