Immunomodulatory cell therapy in sepsis: have we learnt lessons from the past?

Sepsis still constitutes a public health challenge worldwide since its incidence constantly increases over time but its related mortality remains more or less constant. There is thus an unquestionable and urgent need to develop innovative and efficacious therapies for the treatment of this deadly disease. In this study, the authors propose that injection of mesenchymal stem cells rescues mice from death after septic shock owing to their potent immunosuppressive and anti-inflammatory properties. The authors conclude that immunomodulatory cell therapy may represent an effective treatment for sepsis. While the potential therapeutic value of these cells is not to be challenged, considering the present lack of convincing data about mesenchymal stem cell use in sepsis, we do not believe that they constitute the next topical clinical trial in the field. Rather, recent evidence indicates that most septic patients actually present with profound immune alterations suggesting that anti-inflammatory approaches could deleteriously amplify this state. Therefore, in this article, we propose hypotheses explaining why the future of clinical trials in sepsis immunology will likely rely on stimulating immune functions for rebalancing immune homeostasis.