Mitochondria-Rich Fraction Isolated From Mesenchymal Stromal Cells Reduces Lung and Distal Organ Injury in Experimental Sepsis∗

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dc.coverageDOI: 10.1097/CCM.0000000000005056
dc.creatorDe Carvalho, Luiza Rachel Pinheiro
dc.creatorAbreu, Soraia Carvalho
dc.creatorDe Castro, Ligia Lins
dc.creatorAndrade Da Silva, Luísa Helena
dc.creatorSilva, Paula Matos
dc.creatorVieira, Juliana Borges
dc.creatorSantos, Renata Trabach
dc.creatorCabral, Marianna Ribeiro
dc.creatorKhoury, Maroun
dc.creatorWeiss, Daniel J.
dc.creatorLopes-Pacheco, Miquéias
dc.creatorSilva, Pedro Leme
dc.creatorCruz, Fernanda Ferreira
dc.creatorRocco, Patricia Rieken Mac Edo
dc.date2021
dc.date.accessioned2025-11-18T19:41:25Z
dc.date.available2025-11-18T19:41:25Z
dc.description<p>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 × 10<sup>6</sup>) 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.</p>eng
dc.identifierhttps://investigadores.uandes.cl/en/publications/20703057-889f-4dda-8b67-e3e4651cd586
dc.identifier.urihttps://repositorio.uandes.cl/handle/uandes/51807
dc.languageeng
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.sourcevol.49 (2021) nr.9 p.E880-E890
dc.subjectanimal model
dc.subjectcritical illness
dc.subjectinflammation
dc.subjectmitotherapy
dc.subjectoxidative stress
dc.subjectremodeling
dc.titleMitochondria-Rich Fraction Isolated From Mesenchymal Stromal Cells Reduces Lung and Distal Organ Injury in Experimental Sepsis∗eng
dc.typeArticleeng
dc.typeArtículospa
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