Abstract
ALI/ARDS remain the main reason of morbidity and mortality in the critically ill. Studies have indicated that human umbilical cord mesenchymal stem cells (hUC-MSCs) can be useful in the treatment of ALI/ARDS. Sphingosine-1-phosphate (S1P) and its analog FTY720 significantly reduce lipopolysaccharide (LPS)-induced lung edema and inflammatory lung injury. This study aimed to assess the therapeutic effects of hUC-MSCs combined with FTY720 in an LPS-induced murine model of ALI. Eight-week-old female C57BL/6 mice were divided into a normal control group, an LPS group, an hUC-MSC group, an FTY720 group, and an hUC-MSCs+FTY720 group randomly. At 24 hours post injury, mice were administrated hUC-MSCs via the tail vein and/or intraperitoneally injected with FTY720. We assessed histopathology and histologic scores, lung wet/dry weight ratio, micro-CT scans, and total protein in the bronchoalveolar lavage fluid (BALF), as well as cytokines in the BALF at 48 h post injury. All treatment groups showed higher survival rates and attenuated lung injuries. The hUC-MSCs+FTY720 group yielded better results than hUC-MSCs or FTY720 alone. While the underlying mechanism requires further study, we anticipate that combination therapy of hUC-MSCs and FTY720 could be an effective strategy for ALI.
Highlights
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) both can result in acute respiratory failure, and are remain the main reasons of death of critically ill patients [1]
While the underlying mechanism requires further study, we anticipate that combination therapy of hUC-MSCs and FTY720 could be an effective strategy for ALI
The results showed that compared with the LPS+phosphate buffer saline. MCP-1 (PBS) group, mice in LPS+hUC-MSCs, LPS+FTY720, and LPS+human umbilical cord mesenchymal stem cells (hUCMSCs)+FTY720 groups showed clearly attenuated inflammation in the lungs after LPS challenge (Figure 1)
Summary
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) both can result in acute respiratory failure, and are remain the main reasons of death of critically ill patients [1]. These syndromes are induced by various clinical diseases and are characterized by serious intractable hypoxemia and increased inspired oxygen fraction [2]. In several researches [8, 9], MSCs are able to improve pathological damage, reduce inflammation, and even reduce mortality in a mouse model of ALI/ ARDS These researches manifest that hUC - MSCs could be a new method of treatment for ALI/ ARDS [7]
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