Background The use of mesenchymal stem cells (MSCs) is being extensively studied in clinical trials in the setting of various diseases including diabetes, stroke, and progressive multiple sclerosis. The unique immunomodulatory properties of MSCs also point them as a possible therapeutic tool during sepsis and septic shock, a devastating syndrome associated with 30–35% mortality. However, MSCs are not equal regarding their activity, depending on their tissue origin. Here, we aimed at comparing the in vivo properties of MSCs according to their tissue source (bone marrow (BM) versus Wharton’s jelly (WJ)) in a murine cecal ligation and puncture (CLP) model of sepsis that mimics a human peritonitis. We hypothesized that MSC properties may vary depending on their tissue source in the setting of sepsis. Methods CLP, adult, male, C57BL/6 mice were randomized in 3 groups receiving respectively 0.25 × 10 6 BM-MSCs, 0.25 × 10 6 WJ-MSCs, or 150 μL phosphate-buffered saline (PBS) intravenously 24 h after the CLP procedure. Results We observed that both types of MSCs regulated leukocyte trafficking and reduced organ dysfunction, while only WJ-MSCs were able to improve bacterial clearance and survival. Conclusion This study highlights the importance to determine the most appropriate source of MSCs for a given therapeutic indication and suggests a better profile for WJ-MSCs during sepsis.
BackgroundSeptic shock is the leading cause of death in intensive care units. The pathophysiological complexity of this syndrome contributes to an absence of specific treatment. Several preclinical studies in murine models of septic shock have shown improvements to organ injury and survival after administration of mesenchymal stem cells (MSCs). To better mimic a clinical approach in humans, we investigated the impact of randomized controlled double-blind administration of clinical-grade umbilical cord-derived MSCs to a relevant pig model of septic shock.MethodsSeptic shock was induced by fecal peritonitis in 12 male domestic pigs. Animals were resuscitated by an experienced intensivist including fluid administration and vasopressors. Four hours after the induction of peritonitis, pigs were randomized to receive intravenous injection of thawed umbilical cord-derived MSCs (UCMSC) (1 × 106 UCMSCs/kg diluted in 75 mL hydroxyethyl starch (HES), (n = 6) or placebo (HES alone, n = 6). Researchers were double-blinded to the treatment administered. Hemodynamic parameters were continuously recorded. Gas exchange, acid-base status, organ function, and plasma cytokine concentrations were assessed at regular intervals until 24 h after the onset of peritonitis when animals were sacrificed under anesthesia.ResultsPeritonitis induced profound hypotension, hyperlactatemia, and multiple organ failure. These disorders were significantly attenuated when animals were treated with UCMSCs. In particular, cardiovascular failure was attenuated, as attested by a better mean arterial pressure and reduced lactatemia, despite lower norepinephrine requirements. As such, UCMSCs improved survival in this very severe model (60% survival vs. 0% at 24 h).ConclusionUCMSCs administration is beneficial in this pig model of polymicrobial septic shock.
During spaceflight, organisms are subjected to various physical stressors including modification of gravity (G) that, associated with lifestyle, could lead to impaired immunity, intestinal dysbiosis and thus potentially predispose astronauts to illness. Whether space travel affects microbiota homeostasis has not been thoroughly investigated. The aim of this study was to evaluate changes in intestinal microbiota and mucosa in a ground-based murine model consisting in a 21-days confinement of mice in a centrifuge running at 2 or 3G. Results revealed an increased α-diversity and a significant change in intracaecal β-diversity observed only at 3G, with profiles characterized by a decrease of the Firmicutes / Bacteroidetes ratio. Compared to 1G microbiota, 12.1% of the taxa were significantly impacted in 3G microbiota, most of them (78%) being enriched. This study shows a G-level-dependent disruption of intracaecal microbiota, without alteration of mucosal integrity. These first data reinforce those recently obtained with in-flight experimentations or microgravity models, and emphasize the critical need for further studies exploring the impact of spaceflight on intestinal microbiota in order to optimize long-term space travel conditions.
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