Mesenchymal Stem Cells Attenuate Myocardial Functional Depression and Reduce Systemic and Myocardial Inflammation during Endotoxemia

Paeoniflorin improves survival in LPS-challenged mice through the suppression of TNF-α and IL-1β release and augmentation of IL-10 production

“…However, Pae did not significantly enhance cardiac IL-10 content in LPS-challenged mice (data not shown). Recently, several investigators have also demonstrated that treatment with mesenchymal stem cells during endotoxemia reduces myocardial inflammation and functional depression without increasing myocardial IL-10 content [22]. Therefore, myocardial IL-10 might not be responsible for the inhibitory effect of Pae on myocardial TNF-α production during endotoxemia.…”

Advances in Mesenchymal Stem Cell Research in Sepsis

“…While the institution of aggressive supportive strategies now allows the majority of septic patients to survive this initial proinflammatory phase, organ damage resulting from this phase remains a significant cause of morbidity. MSCs ameliorate this potential injury through an overall reduction in both local and systemic inflammation by a balanced decrease in proinflammatory cytokine production and an increase in anti-inflammatory cytokine production [15,46,55]. Important players in the anti-inflammatory cytokine profile of MSCs include transforming growth factor (TGF)-b, IL-10, IL-13, and TNF-a stimulated gene/protein 6 (TSG-6) [10,13].…”

“…Important players in the anti-inflammatory cytokine profile of MSCs include transforming growth factor (TGF)-b, IL-10, IL-13, and TNF-a stimulated gene/protein 6 (TSG-6) [10,13]. MSC-mediated down-regulation of proinflammatory cytokines TNF-a, IL-1, and IL-6 also contributes to the diminished inflammatory milieu [15,52]. The reduced inflammatory state is an especially important consideration for the cytokine dysregulation observed in sepsis.…”

“…However, because of MSC-specific major histocompatibility complex (MHC) profiles and immunomodulatory properties, allogeneic transplantation of stem cells remains a therapeutic possibility [122], and MHC-typed stem cell banks with ready-to-transplant reserves for acute therapies are also plausible. While there are currently no human trials underway to evaluate the efficacy or safety of MSCs in the management of sepsis, an expanding body of animal research data exists, which demonstrates the potential benefits of cellbased therapy for the septic patient (see Table 1) [15,16,30,46,71,75,76]. One of the first studies utilizing MSCs in a mouse endotoxemia model was performed by Xu and colleagues in 2007 [16].…”

“…An ever growing variety of stem cell types and sources have been described to date and a number of phase I, II, and III clinical trials have been undertaken to evaluate their clinical utility in a variety of human diseases [12]. While it was initially believed that the greatest potential of stem cells resided in their ability to engraft and differentiate into the cell types of injured organs, it has now been well established that they also exhibit a range of beneficial abilities, including homing to sites of injury, down-regulating the inflammatory cascade, preventing apoptosis in threatened tissues, promoting neoangiogenesis, activating resident stem cells, and modulating the activity of multiple immune cell types [13][14][15][16][17]. These features make stem cells an extremely attractive therapy in addressing both the proinflammatory response of early sepsis as well as the widespread organ dysfunction which develops thereafter.…”