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

• Published in: Critical care (London, England) Vol. 25; no. 1; pp. 20 - 12
• Main Authors: Hwang, Jung Wook, Lee, Min Ji, Chung, Tae Nyoung, Lee, Han A. Reum, Lee, Jung Ho, Choi, Seo Yoon, Park, Ye Jin, Kim, Chul Hee, Jin, Isom, Kim, Seong Hoon, Kwak, Hyo-Bum, Heo, Jun-Won, Na, Kwangmin, Choi, Sangchun, Choi, Yong-Soo, Kim, Kyuseok
• Format: Journal Article
• Language: English
• Published: London BioMed Central 07.01.2021; BioMed Central Ltd; BMC
• Subjects: Apoptosis; Care and treatment; Cells; Critical care; Critical Care Medicine; Drug development; Drugs; Emergency Medicine; Experiments; Health aspects; Hyperinflammation; Immune modulation; Immune paralysis; Immune response; Intensive; Medicine; Medicine & Public Health; Mitochondria; Mitochondria dysfunction; Mitochondria transplantation; Sepsis; Spleen; Transplantation; South Korea; United States > US; California; Mitochondria transplantation; Hyperinflammation; Sepsis; Mitochondria dysfunction; Immune modulation; Immune paralysis
• ISSN: 1364-8535; 1466-609X; 1364-8535; 1466-609X; 1366-609X
• DOI: 10.1186/s13054-020-03436-x

Background Sepsis 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. Methods We 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. Results Mitochondrial 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. Conclusions In rat polymicrobial cecal slurry model, the outcome is improved by mitochondrial transplantation, which might have an immunomodulatory effect.