期刊
EXPERIMENTAL CELL RESEARCH
卷 399, 期 2, 页码 -出版社
ELSEVIER INC
DOI: 10.1016/j.yexcr.2021.112473
关键词
Sepsis; Mesenchymal stromal cell; Umbilical cord; Bone marrow; Cecal ligation and puncture; Inflammation; Macrophage; Gene expression
资金
- Canadian Institutes of Health Research [MOP-130331, OCN 126573]
- Early Research Award from the Ministry of Research and Innovation [ER 10-07-182]
- Ontario Graduate Scholarship
- St. Michael's Hospital Li Ka Shing Knowledge Institute Graduate Scholarship
Comparative study on the therapeutic effects of bone marrow-derived MSCs (BM-MSCs) and umbilical cord-derived MSCs (UC-MSCs) in a mouse model of polymicrobial sepsis showed significant differences in gene expression profile, surface markers, and therapeutic potency between the two MSC types. BM-MSCs improved survival with enhanced bacterial clearance and improved inflammatory profile post CLP surgery, while UC-MSCs did not enhance survival or bacterial clearance despite some improvement in the inflammatory profile of septic animals.
Sepsis is a complicated multi-system disorder characterized by a dysregulated host response to infection. Despite substantial progress in the understanding of mechanisms of sepsis, translation of these advances into clinically effective therapies remains challenging. Mesenchymal Stromal Cells (MSCs) possess immunomodulatory properties that have shown therapeutic promise in preclinical models of sepsis. The therapeutic effects of MSCs may vary depending on the source and type of these cells. In this comparative study, the gene expression pattern and surface markers of bone marrow-derived MSCs (BM-MSCs) and umbilical cord-derived MSCs (UC-MSCs) as well as their therapeutic effects in a clinically relevant mouse model of polymicrobial sepsis, cecal ligation and puncture (CLP), were investigated. The results showed remarkable differences in gene expression profile, surface markers and therapeutic potency in terms of enhancing survival and pm/anti-inflammatory responses between the two MSC types. BM-MSCs improved survival concomitant with an enhanced systemic bacterial clearance and improved inflammatory profile post CLP surgery. Despite some improvement in the inflammatory profile of the septic animals, treatment with UC-MSCs did not enhance survival or bacterial clearance. Overall, the beneficial therapeutic effects of BM-MSCs over UC-MSCs may likely be attributed to their pro-inflammatory function, and to some extent anti-inflammatory features, reflected in their gene expression pattern enhancing macrophage polarization to M1/M2 phenotypes resulting in a balanced pm- and anti-inflammatory response against polymicrobial sepsis.
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