• Crit Care · Jan 2021

    The immune modulatory effects of mitochondrial transplantation on cecal slurry model in rat.

    • Jung Wook Hwang, Min Ji Lee, Tae Nyoung Chung, Han A Reum Lee, Jung Ho Lee, Seo Yoon Choi, Ye Jin Park, Chul Hee Kim, Isom Jin, Seong Hoon Kim, Hyo-Bum Kwak, Jun-Won Heo, Kwangmin Na, Sangchun Choi, Yong-Soo Choi, and Kyuseok Kim.
    • Department of Biotechnology, CHA University, Gyeonggi-Do, South Korea.
    • Crit Care. 2021 Jan 7; 25 (1): 20.

    BackgroundSepsis has a high mortality rate, but no specific drug has been proven effective, prompting the development of new drugs. Immunologically, sepsis can involve hyperinflammation, immune paralysis, or both, which might pose challenges during drug development. Recently, mitochondrial transplantation has emerged as a treatment modality for various diseases involving mitochondrial dysfunction, but it has never been tested for sepsis.MethodsWe isolated mitochondria from L6 muscle cells and umbilical cord mesenchymal stem cells and tested the quality of the isolated mitochondria. We conducted both in vivo and in vitro sepsis studies. We investigated the effects of intravenous mitochondrial transplantation on cecal slurry model in rats in terms of survival rate, bacterial clearance rate, and the immune response. Furthermore, we observed the effects of mitochondrial transplantation on the immune reaction regarding both hyperinflammation and immune paralysis. To do this, we studied early- and late-phase cytokine production in spleens from cecal slurry model in rats. We also used a lipopolysaccharide (LPS)-stimulated human PBMC monocyte model to confirm the immunological effects of mitochondrial transplantation. Apoptosis and the intrinsic apoptotic pathway were investigated in septic spleens.ResultsMitochondrial transplantation improved survival and bacterial clearance. It also mitigated mitochondrial dysfunction and apoptosis in septic spleens and attenuated both hyperinflammation and immune paralysis in the spleens of cecal slurry model in rats. This effect was confirmed with an LPS-stimulated human PBMC study.ConclusionsIn rat polymicrobial cecal slurry model, the outcome is improved by mitochondrial transplantation, which might have an immunomodulatory effect.

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