Abstract

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.

Details

Title
The immune modulatory effects of mitochondrial transplantation on cecal slurry model in rat
Author
Hwang, Jung Wook; Min Ji Lee; Chung, Tae Nyoung; Reum Lee, Han A; Jung Ho Lee; Seo Yoon Choi; Ye Jin Park; Kim, Chul Hee; Isom, Jin; Kim, Seong Hoon; Kwak, Hyo-Bum; Jun-Won Heo; Na, Kwangmin; Choi, Sangchun; Yong-Soo, Choi; Kyuseok Kim  VIAFID ORCID Logo 
Pages
1-12
Section
Research
Publication year
2021
Publication date
2021
Publisher
BioMed Central
ISSN
13648535
e-ISSN
1366609X
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2478725015
Copyright
© 2021. This work is licensed under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.