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Early effects of bone marrow-derived mononuclear cells on lung and kidney in experimental sepsis
Carla M Silva1, Debora S Ornellas2, Felipe M Ornellas3
1Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil; Laboratory of Cellular and Molecular Physiology, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil; National Institute of Science and Technology for Regenerative Medicine, Rio de Janeiro, Brazil.
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 histology and molecular biology after 6, 12, and 24 h.
Results:
In lungs, BMDMCs reduced the lung injury score and keratinocyte chemoattractant mRNA expression regardless of the time point of analysis; interleukin-10 mRNA content was higher in CLP-cell than CLP-saline at 6 and 24 h. In kidneys, BMDMCs reduced neutrophil gelatinase-associated lipocalin levels at all time points. BMDMCs decreased surface high mobility group box (HMGB)- 1 but increased nuclear HMGB-1 levels.
Conclusion:
Early BMDMC therapy reduced lung and kidney damage in a time-dependent manner.
Insights
Early therapy with bone marrow-derived mononuclear cells (BMDMCs) significantly reduced lung and kidney damage in experimental sepsis. This study highlights BMDMCs as a promising therapeutic agent for sepsis-induced organ injury.
Area of Science:
- Regenerative Medicine
- Immunology
- Sepsis Research
Background:
- Sepsis is a life-threatening condition characterized by a dysregulated host response to infection.
- Previous studies explored bone marrow-derived mononuclear cells (BMDMCs) in lung injury models, but early effects on both lung and kidney in polymicrobial sepsis remain unclear.
Purpose of the Study:
- To investigate the early therapeutic effects of BMDMC administration on lung and kidney damage in a mouse model of experimental polymicrobial sepsis.
Main Methods:
- Cecal ligation and puncture (CLP) was used to induce sepsis in female C57BL/6 mice.
- Animals received either saline or 10^6 BMDMCs intravenously 1 hour post-CLP.
- Lungs and kidneys were analyzed for histological damage and molecular markers at 6, 12, and 24 hours.
Main Results:
- BMDMCs reduced lung injury scores and keratinocyte chemoattractant (KC) mRNA expression in lungs.
- Kidney analysis revealed reduced tubular injury, neutrophil gelatinase-associated lipocalin (NGAL), and altered high-mobility-group-box (HMGB)-1 levels post-BMDMC treatment.
- Interleukin-10 (IL-10) mRNA levels were elevated in BMDMC-treated groups at specific time points.
Conclusions:
- Early intravenous BMDMC therapy effectively mitigated lung and kidney damage in experimental polymicrobial sepsis.
- BMDMCs demonstrate potential as a therapeutic strategy for managing sepsis-induced organ dysfunction.
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