Treating chronic sepsis with adipose derived stem cells

Sepsis is defined as a deregulated immune response to an infection. Despite years of research, no adequate therapy exists and many septic patients die. Especially older people, who survive the acute phase of the disease subsequently develop severe physiological, mental and immunological impairments. In this bilateral project, veterinarian Susanne Drechsler, from the Ludwig Boltzmann Institute for Experimental and Clinical Traumatology in Vienna, and medical doctor Tomasz Skirecki from the Medical Center of Postgraduate Education in Warsaw, will investigate whether treatment with adipose-derived stem cells alleviates the chronic consequences of sepsis. The underlying mechanisms of chronic sepsis will be investigated by using old mice (the Austrian team) and so-called humanized mice containing human immune cells (the Polish team). Both teams will use the same animal model of sepsis und study the influence of the disease on physiologic and mental parameters as well as on the immune system and metabolism. This study aims to fill the current knowledge gaps regarding the long -term consequences of sepsis and therapeutic potential of adipose-derived stem cells to optimize their use in clinical trials.

This project established a long-term model of post-septic chronic complications in aged septic mice and, with the Polish partner, developed an advanced humanized mouse model of sepsis. Together, these models revealed how sepsis causes lasting muscle damage and immune dysfunction, while also showing that a stem-cell therapy can meaningfully improve survival and recovery. Sepsis is the body's extreme and often damaging response to infection and remains a leading cause of death in intensive care. Many survivors go on to suffer long-term problems-chronic muscle weakness, cognitive difficulties, and lasting immune impairment-collectively known as PICS (Persistent Inflammation, Immunosuppression, and Catabolism Syndrome). Studying these consequences requires animal models that closely mirror the human immune system, which standard mice do not provide. To address this, the project built two complementary platforms. The first uses regular mice at adult and old age, matching the demographics of human patients. The second uses a new "humanized" mouse model (MISTRG6), created by transplanting human blood-forming cells into mice so that much of their immune system is genuinely human. Both platforms were used to model sepsis closely resembling infections seen in patients. The results showed that sepsis causes deep, lasting damage well beyond the initial infection. In skeletal muscle, sepsis disrupted the cellular systems maintaining healthy mitochondria, leading to structural damage, reduced energy output, and ongoing muscle-cell death for weeks after infection resolved-offering one of the first mechanistic explanations for the chronic muscle weakness seen in PICS. Detailed immune profiling of bone marrow, spleen, and abdominal fluid mapped how immune cells are recruited, activated, and ultimately exhausted during and after sepsis. Mice also showed lasting behavioral and cognitive changes mirroring those reported in human survivors. The project also tested an experimental cell therapy using human adipose-derived stem cells (hASC). Preliminary data show treated animals had a lower death rate (35% vs. 46% in untreated controls), a favorable trend toward reduced risk of death, milder early weight loss, and faster recovery of temperature and weight-all without safety concerns such as coagulopathy. This part of the project is ongoing, with more definitive data expected within months. Current results strongly suggest real translational promise, though the survival benefit has not yet reached statistical significance. Together, these findings establish a powerful new platform for studying sepsis in a clinically realistic way and point toward a possible cell-based treatment for its aftermath. Subsequent analyses of the therapy's long-term effects on muscle and mitochondrial recovery are expected to yield further important results.