Human umbilical cord mesenchymal stem cell-derived mitochondria (PN-101) attenuate LPS-induced inflammatory responses by inhibiting NFκB signaling pathway

Abstract

Inflammation is one of the body’s natural responses to injury and illness as part of the healing process. However, persistent inflammation can lead to chronic inflammatory diseases and multi-organ failure. Altered mitochondrial function has been implicated in several acute and chronic inflammatory diseases by inducing an abnormal inflammatory response. Therefore, treating inflammatory diseases by recovering mitochondrial function may be a potential therapeutic approach. Recently, mitochondrial transplantation has been proven to be beneficial in hyperinflammatory animal models. However, it is unclear how mitochondrial transplantation attenuates inflammatory responses induced by external stimuli. Here, we isolated mitochondria from umbilical cord-derived mesenchymal stem cells, referred as to PN-101. We found that PN-101 could signifi-cantly reduce LPS-induced mortality in mice. In addition, in phorbol 12-myristate 13-acetate (PMA)-treated THP-1 macrophages, PN-101 attenuated LPS-induced increase production of pro-inflammatory cytokines. Furthermore, the anti-inflammatory effect of PN-101 was mediated by blockade of phosphorylation, nuclear translocation, and trans-activity of NFκB. Taken together, our results demonstrate that PN-101 has therapeutic potential to attenuate pathological inflammatory responses.

Exploration of drug resistance mechanisms in triple negative breast cancer cells using a microfluidic device and patient tissues

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Exploration of Mechanisms of Drug Resistance in a Microfluidic Device and Patient Tissues

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Therapeutic potential of mitochondrial transplantation in modulating immune responses post-cardiac arrest: a narrative review

“…Similarly, in osteoarthritis, mitochondria derived from bone marrow mesenchymal stem cells have been found to enhance chondrocyte function and stimulate mitochondrial biogenesis, contributing to joint health [ 77 ]. Human MSC-derived mitochondria have shown promise in attenuating LPS-induced inflammatory responses by inhibiting the nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) signaling pathway [ 78 ]. Further, a link between mitochondrial health in neurodevelopment and brain functioning in adulthood was established in a maternal immune activation model of schizophrenia in rats [ 79 ].…”