The Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA 94143, USA.
Stem Cells. 2010 Dec;28(12):2229-38. doi: 10.1002/stem.544.
Recent in vivo studies indicate that mesenchymal stem cells (MSCs) may have beneficial effects in the treatment of sepsis induced by bacterial infection. Administration of MSCs in these studies improved survival and enhanced bacterial clearance. The primary objective of this study was to test the hypothesis that human MSCs possessed intrinsic antimicrobial properties. We studied the effect of human MSCs derived from bone marrow on the bacterial growth of Gram-negative (Escherichia coli and Pseudomonas aeruginosa) and Gram-positive (Staphylococcus aureus) bacteria. MSCs as well as their conditioned medium (CM) demonstrated marked inhibition of bacterial growth in comparison with control medium or normal human lung fibroblasts (NHLF). Analysis of expression of major antimicrobial peptides indicated that one of the factors responsible for the antimicrobial activity of MSC CM against Gram-negative bacteria was the human cathelicidin antimicrobial peptide, hCAP-18/LL-37. Both m-RNA and protein expression data showed that the expression of LL-37 in MSCs increased after bacterial challenge. Using an in vivo mouse model of E. coli pneumonia, intratracheal administration of MSCs reduced bacterial growth (in colony-forming unit) in the lung homogenates and in the bronchoalveolar lavage (BAL) fluid, and administration of MSCs simultaneously with a neutralizing antibody to LL-37 resulted in a decrease in bacterial clearance. In addition, the BAL itself from MSC-treated mice had a greater antimicrobial activity in comparison with the BAL of phosphate buffered saline (PBS)-treated mice. Human bone marrow-derived MSCs possess direct antimicrobial activity, which is mediated in part by the secretion of human cathelicidin hCAP-18/ LL-37.
最近的体内研究表明，间充质干细胞（MSCs）可能对治疗由细菌感染引起的败血症具有有益作用。在这些研究中，给予 MSCs 可提高存活率并增强细菌清除率。本研究的主要目的是检验以下假设，即人 MSCs 具有内在的抗菌特性。我们研究了源自骨髓的人 MSCs 对革兰氏阴性（大肠杆菌和铜绿假单胞菌）和革兰氏阳性（金黄色葡萄球菌）细菌的细菌生长的影响。与对照培养基或正常人肺成纤维细胞（NHLF）相比，MSCs 及其条件培养基（CM）显示出对细菌生长的明显抑制作用。对抗菌肽表达的分析表明，MSC CM 对革兰氏阴性菌的抗菌活性的一个原因是人类防御素抗菌肽 hCAP-18/LL-37。mRNA 和蛋白表达数据均表明，细菌攻击后 MSC 中 LL-37 的表达增加。在大肠杆菌肺炎的体内小鼠模型中，气管内给予 MSCs 可减少肺匀浆和支气管肺泡灌洗液（BAL）中的细菌生长（菌落形成单位），并且同时给予 MSC 和针对 LL-37 的中和抗体可导致细菌清除减少。此外，与用磷酸盐缓冲盐水（PBS）处理的小鼠的 BAL 相比，用 MSC 处理的小鼠的 BAL 具有更大的抗菌活性。人骨髓源性 MSCs 具有直接的抗菌活性，部分通过人防御素 hCAP-18/LL-37 的分泌介导。
