The mortality rate of critically ill patients with acute respiratory distress syndrome (ARDS) is 30.9% to 46.1%. The emergence of the coronavirus disease 2019 (Covid-19) has become a global issue with raising dire concerns. Patients with severe Covid-19 may progress toward ARDS. Mesenchymal stem cells (MSCs) can be derived from bone marrow, umbilical cord, adipose tissue and so on. The easy accessibility and low immunogenicity enable MSCs for allogeneic administration, and thus they were widely used in animal and clinical studies. Accumulating evidence suggests that mesenchymal stem cell infusion can ameliorate ARDS. However, the underlying mechanisms of MSCs need to be discussed. Recent studies showed MSCs can modulate immune/inflammatory cells, attenuate endoplasmic reticulum stress, and inhibit pulmonary fibrosis. The paracrine cytokines and exosomes may account for these beneficial effects. In this review, we summarize the therapeutic mechanisms of MSCs in ARDS, analyzed the most recent animal experiments and Covid-19 clinical trial results, discussed the adverse effects and prospects in the recent studies, and highlight the potential roles of MSC therapy for Covid-19 patients with ARDS.

Objectives: Abnormal rheological properties induce adverse effects during sepsis. This study sought to investigate the hypothesis that resveratrol (Res) improves blood rheological properties in rats following a lipopolysaccharide (LPS) challenge, and provide a novel approach for treatment of sepsis. Methods: The rats were intraperitoneally or intramuscularly injected with vehicle, LPS (8 mg/kg), Res (30 mg/kg), or both to yield four groups: control, Res, LPS, and LPS + Res. After 6 h of LPS and/or Res injection, the mean arterial pressure (MAP), regional blood flow, erythrocyte and leukocyte parameters, and blood viscosity were observed. Results: LPS administration had no significant effects on the erythrocyte parameters and plasma viscosity. LPS administration reduced the MAP, whole blood viscosity at low and medium shear rates, the blood flow in the spleen and kidney, and the leukocyte content in whole blood when compared to control group, and increased the myeloperoxidase (MPO) activity in lung. Treatment with Res alone had no effects on most of parameters observed except increasing the whole blood relative viscosity. However, Res treatment after LPS resulted in further decrease in whole blood viscosity at high and medium shear rates. Furthermore, Res treatment conversely decreased the red blood cell distribution width-CV, blood flow of stomach, whole blood relative viscosity and MPO activity in lung, and increased the leukocyte content, but did not restore LPS-induced decrease in MAP and the blood flow in the spleen and kidney. Conclusion: The Res treatment partly reduce the whole blood viscosity and regional blood flow, and increase WBC content in peripheral blood following the LPS challenge, suggesting a favorable role in expanding the quasi-sympathetic effects of LPS in blood viscosity at early stages.

Background: The kidney is a common target in multiple organ dysfunction syndrome (MODS). The aim of this study is to determine the role of intestinal lymphatic pathway on renal injury in hemorrhagic shock rats. Methods: Wistar rats were divided into sham, shock, and ligation groups. The hemorrhagic shock model was induced in the shock and ligation groups. After resuscitation, the mesenteric lymph ducts were ligated in the ligation group. Blood from the carotid artery was taken to determine renal functional indices. The kidneys were used to observe histomorphological changes at 6 h after resuscitation. In addition, kidney homogenate was used to determine malondialdehyde (MDA), superoxide dismutase (SOD), tumor necrosis factor alpha (TNFα), interleukin-6 (IL-6), and myeloperoxidase (MPO) levels at 90 min after shock and 0, 1, 3, 6, 12, and 24 h after resuscitation. And the survival rate of 24 h was recorded. Results: The survival rate in shock group was obviously lower than sham and ligation groups. The urea and creatinine contents in the serum of shock and ligation groups were significantly higher than the sham group; the indices in the ligation group were significantly lower than the shock group. Histological studies showed various degrees of renal injury in the shock and ligation groups with a lesser severity in the ligation group. MDA, TNFα, IL-6, and MPO in renal homogenate of the shock group were raised, and the activity of SOD was lower in comparison to the sham group. Further, MDA, TNFα, IL-6, and MPO in renal homogenate of the ligation group at 6, 12, and 24 h were lower, and the SOD activity was higher than that of the shock group at the same time points. Conclusion: The mesenteric lymph duct ligation could be used to attenuate renal injury in shock rats. Its mechanism might be related to reducing the polymorph nuclear (PMN) and decreasing inflammatory mediator and free radical.

Vascular hyporeactivity is an important factor in irreversible shock, whereas calcium desensitization is one of the mechanisms of vascular hyporeactivity, and the intestinal lymphatic pathway plays an important role in multiple organ injury after severe hemorrhagic shock (HS). In this study, our aims were to determine the effects of mesenteric lymph on vascular reactivity during HS and the mechanisms involved. First, the in vivo pressor response was observed by intravenous injection of norepinephrine (3 μg/kg) at different time points after HS. We found that mesenteric lymph duct ligation (MLDL) and mesenteric lymph drainage (MLD) enhanced the pressor response at multiple time points after shock. Next, vascular reactivity and calcium sensitivity in superior mesenteric artery (SMA) vascular rings were examined using an isolated organ perfusion system. Vascular reactivity and calcium sensitivity were higher for SMA rings from rats that had undergone HS plus MLDL or MLD that those from rats that had undergone only HS. The effects of MLDL and MLD on vascular reactivity and calcium sensitivity were significantly increased following incubation with the calcium sensitizer angiotensin II and were reduced after incubation with the calcium sensitivity inhibitor insulin. When SMA rings from normal rats were incubated with mesenteric lymph from rats subjected to HS, lymph obtained 0 to 0.5 h after shock enhanced vascular reactivity and calcium sensitivity, whereas lymph obtained 1 to 3 h after shock blunted these effects. We finally examined vascular reactivity and calcium sensitivity in HS rats subjected to MLD at 0 to 3 h or 1 to 3 h after shock. We found that contractile activity of SMAs in response to norepinephrine or Ca²⁺ was higher in HS rats subjected to MLD at 1 to 3 h after shock compared with rats subjected to MLD at 0 to 3 h after shock. These results indicate that mesenteric lymph return plays an important role in biphasic changes in vascular reactivity during HS. Even more importantly, mesenteric lymph 1 h after shock was an important contributor to vascular hyporeactivity, and its mechanism of action was related to calcium desensitization. Targeting lymph may therefore have therapeutic potential in the treatment of severe shock-induced hypotension.

Background: Hemorrhagic shock-induced ischemia and hypoxia elicit endoplasmic reticulum stress (ERS) that leads to cell apoptosis, tissue structural damage and organ dysfunction and failure. Stellate ganglion blockade (SGB) has been demonstrated to improve intestinal barrier dysfunction induced by hemorrhagic shock. The present study sought to investigate whether the beneficial effect of SGB on the intestinal mucosal barrier function is via suppression of ERS.