Early effects of bone marrow-derived mononuclear cells on lung and kidney in experimental sepsis

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Silva, Carla M. ; Ornellas, Debora S. ; Ornellas, Felipe M. ; Santos, Raquel S. ; V. Martini, Sabrina ; Ferreira, Debora ; Muiler, Caroline ; Cruz, Fernanda F. ; Takiya, Christina M. ; Rocco, Patricia R. M. ; Morales, Marcelo M. ; Silva, Pedro L.

• Document type: Journal article
• Source: Respiratory Physiology & Neurobiology; v. 309, p. 10-pg., 2023-03-01.

Abstract

Background: In experimental sepsis, functional and morphological effects of bone marrow-derived mononuclear cell (BMDMC) administration in lung tissue have been evaluated 1 and 7 days after therapy. However, to date no study has evaluated the early effects of BMDMCs in both lung and kidney in experimental polymicrobial sepsis.Material and methods: Twenty-five female C57BL/6 mice were randomly divided into the following groups: 1) cecal ligation and puncture (CLP)-induced sepsis; and 2) Sham (surgical procedure without CLP). After 1 h, CLP animals received saline (NaCl 0.9%) (CLP-Saline) or 106 BMDMCs (CLP-Cell) via the jugular vein. At 6, 12, and 24 h after saline or BMDMC administration, lungs and kidneys were removed for histology and molecular biology analysis.Results: In lungs, CLP-Saline, compared to Sham, was associated with increased lung injury score (LIS) and keratinocyte chemoattractant (KC) mRNA expression at 6, 12, and 24 h. BMDMCs were associated with reduced LIS and KC mRNA expression regardless of the time point of analysis. Interleukin (IL)-10 mRNA content was higher in CLP-Cell than CLP-Saline at 6 and 24 h. In kidney tissue, CLP-Saline, compared to Sham, was associated with tubular cell injury and increased neutrophil gelatinase-associated lipocalin (NGAL) levels, which were reduced after BMDMC therapy at all time points. Surface high-mobility-group-box (HMGB)-1 levels were higher in CLP-Saline than Sham at 6, 12, and 24 h, whereas nuclear HMGB-1 levels were increased only at 24 h. BMDMCs were associated with decreased surface HMGB-1 and increased nuclear HMGB-1 levels. Kidney injury molecule (KIM)-1 and IL-18 gene expressions were reduced in CLP-Cell compared to CLP-Saline at 12 and 24 h.Conclusion: In the present experimental polymicrobial sepsis, early intravenous therapy with BMDMCs was able to reduce lung and kidney damage in a time-dependent manner. BMDMCs thus represent a potential therapy in well-known scenarios of sepsis induction.Purpose: To evaluate early bone marrow-derived mononuclear cell (BMDMC) therapy on lung and kidney in experimental polymicrobial sepsis.Methods: Twenty-five female C57BL/6 mice were randomly divided into the following groups: cecal ligation and puncture (CLP)-induced sepsis; and sham (surgical procedure without CLP). After 1 h, CLP animals received saline (CLP-saline) or 106 BMDMCs (CLP-cell) via the jugular vein. Lungs and kidneys were evaluated for his-tology and molecular biology after 6, 12, and 24 h. (AU)

• FAPESP's process: 18/20403-6 - Biomolecular markers of proliferation and remodeling in acute and chronic respiratory diseases: promising therapeutic targets
• Grantee: Vera Luiza Capelozzi
• Support Opportunities: Research Projects - Thematic Grants