Genome-wide blood transcriptional profiling in human endotoxemia given human adipose-derived mesenchymal stem cells

Mesenchymal stem cells (MSCs) can modulate various immune responses implicated in the pathogenesis of sepsis. Intravenous injection of lipopolysaccharide (LPS) into healthy subjects represents a model with relevance for the host response to sepsis. To determine the effect of MSCs on the early inflammatory response to intravenous LPS we conducted a randomized study in 32 healthy subjects with 4 treatment arms: placebo or adipocyte-derived MSCs intravenously at either 250.000, 1 million or 4 million cells/kg; all subjects received LPS intravenously (2 ng/kg) one hour after the end of MSC infusion. PAXgene blood RNA was isolated before and at 2, 4, 6 and 24 hours after LPS injection. Through the use of genome-wide transcriptional profiling we aimed to identify features of the systemic host transcriptional response to E.coli LPS endotoxemia that were altered due to mesenchymal stem cell administration. Moreover, biological pathway analysis was used to tease out the most relevant biological units.