Mitochondria-Rich Fraction Isolated From Mesenchymal Stromal Cells Reduces Lung and Distal Organ Injury in Experimental Sepsis*
| Autor: | Pedro L. Silva, Paula Matos Silva, Renata Trabach Santos, Luiza Rachel Pinheiro de Carvalho, Fernanda F. Cruz, Miquéias Lopes-Pacheco, Luisa H. A. Silva, Ligia Lins de Castro, J.B. Vieira, Maroun Khoury, Daniel J. Weiss, Soraia C. Abreu, Marianna Ribeiro Cabral, Patricia R. M. Rocco |
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| Rok vydání: | 2021 |
| Předmět: |
Multiple Organ Failure
Inflammation Critical Care and Intensive Care Medicine medicine.disease_cause Andrology Sepsis 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine Animals Lung Liver injury Kidney business.industry Mesenchymal stem cell Mesenchymal Stem Cells 030208 emergency & critical care medicine medicine.disease Mitochondria Mice Inbred C57BL Disease Models Animal medicine.anatomical_structure Liver 030228 respiratory system chemistry Keratinocyte growth factor medicine.symptom business Oxidative stress |
| Zdroj: | Critical Care Medicine. 49:e880-e890 |
| ISSN: | 0090-3493 |
| DOI: | 10.1097/ccm.0000000000005056 |
| Popis: | OBJECTIVES To ascertain whether systemic administration of mitochondria-rich fraction isolated from mesenchymal stromal cells would reduce lung, kidney, and liver injury in experimental sepsis. DESIGN Animal study. SETTING Laboratory investigation. SUBJECTS Sixty C57BL/6 male mice. INTERVENTIONS Sepsis was induced by cecal ligation and puncture; sham-operated animals were used as control. At 24 hours after surgery, cecal ligation and puncture and Sham animals were further randomized to receive saline or mitochondria-rich fraction isolated from mesenchymal stromal cells (3 × 106) IV. At 48 hours, survival, peritoneal bacterial load, lung, kidney, and liver injury were analyzed. Furthermore, the effects of mitochondria on oxygen consumption rate and reactive oxygen species production of lung epithelial and endothelial cells were evaluated in vitro. MEASUREMENTS AND MAIN RESULTS In vitro exposure of lung epithelial and endothelial cells from cecal ligation and puncture animals to mitochondria-rich fraction isolated from mesenchymal stromal cells restored oxygen consumption rate and reduced total reactive oxygen species production. Infusion of exogenous mitochondria-rich fraction from mesenchymal stromal cells (mitotherapy) reduced peritoneal bacterial load, improved lung mechanics and histology, and decreased the expression of interleukin-1β, keratinocyte chemoattractant, indoleamine 2,3-dioxygenase-2, and programmed cell death protein 1 in lung tissue, while increasing keratinocyte growth factor expression and survival rate in cecal ligation and puncture-induced sepsis. Mitotherapy also reduced kidney and liver injury, plasma creatinine levels, and messenger RNA expressions of interleukin-18 in kidney, interleukin-6, indoleamine 2,3-dioxygenase-2, and programmed cell death protein 1 in liver, while increasing nuclear factor erythroid 2-related factor-2 and superoxide dismutase-2 in kidney and interleukin-10 in liver. CONCLUSIONS Mitotherapy decreased lung, liver, and kidney injury and increased survival rate in cecal ligation and puncture-induced sepsis. |
| Databáze: | OpenAIRE |
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