Cryopreserved Stem Cells Incur Damages Due To Terrestrial Cosmic Rays Impairing Their Integrity Upon Long-Term Storage.

Stem cells have the capacity to ensure the renewal of tissues and organs. They could be used in the future for a wide range of therapeutic purposes and are preserved at liquid nitrogen temperature to prevent any chemical or biological activity up to several decades before their use. We show that the cryogenized cells accumulate damages coming from natural radiations, potentially inducing DNA double-strand breaks (DSBs). Such DNA damage in stem cells could lead to either mortality of the cells upon thawing or a mutation diminishing the therapeutic potential of the treatment. Many studies show how stem cells react to different levels of radiation; the effect of terrestrial cosmic rays being key, it is thus also important to investigate the effect of the natural radiation on the cryopreserved stem cell behavior over time. Our study showed that the cryostored stem cells totally shielded from cosmic rays had less DSBs upon long-term storage. This could have important implications on the long-term cryostorage strategy and quality control of different cell banks.

Micro-fragmented fat injection reduces sepsis-induced acute inflammatory response in a mouse model.

BACKGROUND: Severe sepsis has a high mortality rate. There is increasing evidence that human mesenchymal stem cells possess immunomodulatory properties in sepsis, particularly those from adipose tissue. We hypothesised that micro-fragmented human fat, obtained with minimal alteration of the stromal vascular niche, attenuates the inflammatory response and improves outcome in a murine model of sepsis. METHODS: Micro-fragmented fat, lipoaspirate, or saline was administered intraperitoneally 2 h after caecal ligation and puncture (CLP) in C57Bl/6RJ ketamine-xylazine anaesthetised mice. The primary endpoint was the inflammatory score. Secondary endpoints included survival, physiological, histological, and biological parameters. RESULTS: In CLP mice, micro-fragmented fat administration significantly decreased the median (range) inflammatory score compared with saline [17 (14-20) vs 9 (8-12), P=0.006]. Secondary endpoints were also significantly improved in micro-fragmented fat-treated compared with saline-treated CLP mice. Improvement in inflammatory score and in survival was suppressed when micro-fragmented fat was co-administered with liposomes loaded with clodronate (macrophage toxin) or NS-398 (cyclo-oxygenase 2 inhibitor), but not with SC-560 (cyclo-oxygenase 1 inhibitor). CONCLUSIONS: In a murine model of severe sepsis, micro-fragmented fat improved early inflammatory status and outcome, at least in part, by a cyclo-oxygenase-2-mediated mechanism. The potential therapeutic value of micro-fragmented fat in severe sepsis warrants further investigation.

Sepsis induces long-term metabolic and mitochondrial muscle stem cell dysfunction amenable by mesenchymal stem cell therapy.

Sepsis, or systemic inflammatory response syndrome, is the major cause of critical illness resulting in admission to intensive care units. Sepsis is caused by severe infection and is associated with mortality in 60% of cases. Morbidity due to sepsis is complicated by neuromyopathy, and patients face long-term disability due to muscle weakness, energetic dysfunction, proteolysis and muscle wasting. These processes are triggered by pro-inflammatory cytokines and metabolic imbalances and are aggravated by malnutrition and drugs. Skeletal muscle regeneration depends on stem (satellite) cells. Herein we show that mitochondrial and metabolic alterations underlie the sepsis-induced long-term impairment of satellite cells and lead to inefficient muscle regeneration. Engrafting mesenchymal stem cells improves the septic status by decreasing cytokine levels, restoring mitochondrial and metabolic function in satellite cells, and improving muscle strength. These findings indicate that sepsis affects quiescent muscle stem cells and that mesenchymal stem cells might act as a preventive therapeutic approach for sepsis-related morbidity.