Mesenchymal Stem Cells (MSCs) Treatment Alleviates Smoke Inhalation and BurnInduced Acute Respiratory Distress Syndrome (ARDS) by Inhibiting HMGB1-TLR4 Signal
Journal of Immunology(2023)
摘要
Abstract ARDS is one of the leading causes of high morbidity and mortality in trauma patients. Previously our data demonstrated autologous MSCs treatment improved survival in a swine model of smoke inhalation and burn injury. However, the pathophysiological mechanisms are still largely unknown. Twenty anesthetized female swine underwent smoke inhalation injury and 40% TBSA burns, were then randomly assigned to either mock treatment (IC, n=10), or autologous MSCs treatment (MSCs, n=10), followed by ICU care up to 72 hours except in case of early death. Three doses of MSCs collected by bone marrow aspiration and concentrated using a bedside cell concentrator device were applied at 2, 24, and 48 hours of post-injury (PI). Blood and tissue samples were collected for ELISA and IHC analyses. In IC group, 10/10 injured pigs developed ARDS, but only 6/10 pigs in MSCs group developed ARDS. Serum analysis revealed that the HMGB1 level gradually increased after injury and reached a peak at 48h PI (5.7-fold increase vs. baseline). The SDC-1 and C3a levels also increased after injury but reached a peak at 24h (2.9-fold) and 72h PI (2.2-fold), respectively. The MSCs treatment significantly reduced the HMGB1 level in the serum, especially at 6h and 12h PI compared to the IC group but failed to inhibit the SDC-1 and C3a increases. IHC analyses showed that injury triggered a significantly higher expressions of HMGB1 and TLR4, as well as co-localization of HMGB1 and TLR4 in the lung; while MSCs treatment was able to disrupt the HMGB1-TLR4 interaction and significantly reduce their expressions. Our data indicate that the way MSCs treatment mitigates ARDS might be by reducing HMGB1 release and inhibiting the HMGB1-TLR4 signal pathway activation in pigs after smoke and burn injury. This work was supported by the US Army Medical Research and Development Command (USAMRDC) under Grant No. W81XWH-13-2-0005.
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关键词
treatment alleviates smoke inhalation,burn-induced
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