Expanded endothelial progenitor cells mitigate lung injury in septic mice

Abstract

Endothelial progenitor cells (EPCs) improve survival and reduce organ failure in cecal ligation and puncture-induced sepsis; however, expanded EPCs may represent an even better approach for vascular repair. To date, no study has compared the effects of non-expanded EPCs (EPC-NEXP) with those of expanded EPCs (EPC-EXP) and mesenchymal stromal cells of human (MSC-HUMAN) and mouse (MSC-MICE) origin in experimental sepsis. One day after cecal ligation and puncture sepsis induction, BALB/c mice were randomized to receive saline, EPC-EXP, EPC-NEXP, MSC-HUMAN or MSC-MICE (1 × 105) intravenously. EPC-EXP, EPC-NEXP, MSC-HUMAN, and MSC-MICE displayed differences in phenotypic characterization. On days 1 and 3, cecal ligation and puncture mice showed decreased survival rate, and increased elastance, diffuse alveolar damage, and levels of interleukin (IL)-1β, IL-6, IL-10, tumor necrosis factor-α, vascular endothelial growth factor, and platelet-derived growth factor in lung tissue. EPC-EXP and MSC-HUMAN had reduced elastance, diffuse alveolar damage, and platelet-derived growth factor compared to no-cell treatment. Tumor necrosis factor-α levels decreased in the EPC-EXP, MSC-HUMAN, and MSC-MICE groups. IL-1β levels decreased in the EPC-EXP group, while IL-10 decreased in the MSC-MICE. IL-6 levels decreased both in the EPC-EXP and MSC-MICE groups. Vascular endothelial growth factor levels were reduced regardless of therapy. In conclusion, EPC-EXP and MSC-HUMAN yielded better lung function and reduced histologic damage in septic mice.