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2015 ; 6
(ä): 199
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Combination therapy of menstrual derived mesenchymal stem cells and antibiotics
ameliorates survival in sepsis
#MMPMID26474552
Alcayaga-Miranda F
; Cuenca J
; Martin A
; Contreras L
; Figueroa FE
; Khoury M
Stem Cell Res Ther
2015[Oct]; 6
(ä): 199
PMID26474552
show ga
INTRODUCTION: Sepsis is a clinical syndrome associated with a severe systemic
inflammation induced by infection. Although different anti-microbial drugs have
been used as treatments, morbidity and mortality rates remain high. Mesenchymal
stem cells (MSCs) derived from the bone marrow have demonstrated a partial
protective effect in sepsis. Menstrual derived MSCs (MenSCs) emerge as an
attractive candidate because they present important advantages over other
sources, including improved proliferation rates and paracrine response under
specific stress conditions. Here, we evaluate their therapeutic effect in a
polymicrobial severe sepsis model. METHODS: The antimicrobial activity of MenSCs
was determined in vitro through direct and indirect bacterial growth assays and
the measurement of the expression levels of different antimicrobial peptides
(AMPs) by quantitative reverse transcription-polymerase chain reaction. The
therapeutic effect of MenSCs was determined in the cecal ligation and puncture
(CLP) mouse model. Mice were then treated with antibiotics (AB) or MenSCs alone
or in combination. The survival rates and histological and biochemical parameters
were evaluated, and the systemic levels of pro- and anti-inflammatory cytokines
as well as the response of specific lymphocyte subsets were determined by flow
cytometry. RESULTS: MenSCs exerted an important antimicrobial effect in vitro,
mediated by a higher expression of the AMP-hepcidin. In the CLP mouse model,
MenSCs in synergy with AB (a) improved the survival rate (95 %) in comparison
with saline (6 %), AB (73 %), and MenSCs alone (48 %) groups; (b) enhanced
bacterial clearance in the peritoneal fluids and blood; (c) reduced organ
injuries evaluated by lower concentrations of the liver enzymes alanine
aminotransferase and aspartate aminotransferase; and (d) modulated the
inflammatory response through reduction of pro- and anti-inflammatory cytokines
without significant loss of T and B lymphocytes. CONCLUSIONS: We conclude that
MenSCs in combination with AB enhance survival in CLP-induced sepsis by acting on
multiples targets. MenSCs thus constitute a feasible approach for the future
clinical treatment of sepsis.