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Mesenchymal stem cells significantly improved treatment effects of Linezolid on severe pneumonia in a rabbit model
Dexiao Kong1,2, Xia Liu3, Xiaomei Li4
1Department of hematology of the Second Hospital, Institute of Biotherapy for Hematological Malignancies, Shandong University-Karolinska Institute Collaborative Laboratory for Stem Cell Research, Shandong University, Jinan, Shandong Province, China.
Abstract:
The present study aimed to investigate whether co-administration of mesenchymal stromal cells (MSC) and linezolid (LZD) into a rabbit model of methicillin-resistant Staphylococcus aureus (MRSA)-infected pneumonia would bring a synergistic therapeutic effect. Human umbilical cord-derived MSCs (hUMSCs) were isolated and characterized. A rabbit model of pneumonia was constructed by delivering 1 × 1010 CFU MRSA via a bronchoscope into the basal segment of lower lobe of right lung. Through analyzing vital sign, pulmonary auscultation, SpO2, chest imaging, bronchoscopic manifestations, pathology, neutrophil percentage, and inflammatory factors, we verified that a rabbit model of MRSA-induced pneumonia was successfully constructed. Individual treatment with LZD (50 mg/kg for two times/day) resulted in improvement of body weight, chest imaging, bronchoscopic manifestations, histological parameters, and IL-10 concentration in plasma (P<0.01), decreasing pulmonary auscultation, and reduction of IL-8, IL-6, CRP, and TNF-α concentrations in plasma (P<0.01) compared with the pneumonia model group at 48 and 168 h. Compared with LZD group, co-administration of hUMSCs (1 × 106/kg for two times at 6 and 72 h after MRSA instillation) and LZD further increased the body weight (P<0.05). The changes we observed from chest imaging, bronchoscopic manifestations and pathology revealed that co-administration of hUMSCs and LZD reduced lung inflammation more significantly than that of LZD group. The plasma levels of IL-8, IL-6, CRP, and TNF-α in combined group decreased dramatically compared with the LZD group (P<0.05). In conclusion, hUMSCs administration significantly improved therapeutic effects of LZD on pneumonia resulted from MRSA infection in a rabbit model.
Insights
Co-administering human umbilical cord-derived mesenchymal stromal cells (hUMSCs) with linezolid (LZD) synergistically enhanced treatment for methicillin-resistant Staphylococcus aureus (MRSA) pneumonia in rabbits. This combination therapy significantly reduced lung inflammation and improved therapeutic outcomes compared to linezolid alone.
Area of Science:
- * Regenerative Medicine
- * Infectious Diseases
- * Pharmacology
Background:
- * Methicillin-resistant Staphylococcus aureus (MRSA) pneumonia poses a significant therapeutic challenge.
- * Current treatments, including linezolid (LZD), have limitations in fully eradicating infection and inflammation.
- * Mesenchymal stromal cells (MSCs) show potential immunomodulatory and regenerative properties.
Purpose of the Study:
- * To investigate the synergistic therapeutic effect of co-administering mesenchymal stromal cells (MSCs) and linezolid (LZD) in a rabbit model of MRSA-infected pneumonia.
- * To evaluate the impact of this combination therapy on clinical, imaging, pathological, and inflammatory markers.
- * To determine if hUMSCs enhance the efficacy of LZD in treating MRSA pneumonia.
Main Methods:
- * Construction of a rabbit model of MRSA-induced pneumonia via bronchoscopic instillation of MRSA.
- * Administration of linezolid (LZD) alone and in combination with human umbilical cord-derived MSCs (hUMSCs).
- * Comprehensive assessment including vital signs, pulmonary auscultation, SpO2, chest imaging, bronchoscopy, pathology, neutrophil counts, and plasma inflammatory factors (IL-8, IL-6, CRP, TNF-α, IL-10).
Main Results:
- * Linezolid (LZD) monotherapy improved body weight, chest imaging, bronchoscopic manifestations, histology, and IL-10 levels, while reducing pulmonary auscultation findings and other inflammatory markers (IL-8, IL-6, CRP, TNF-α).
- * Co-administration of hUMSCs with LZD resulted in further significant improvements in body weight, chest imaging, bronchoscopic manifestations, and pathology compared to LZD alone.
- * The combination therapy led to a more pronounced reduction in plasma levels of IL-8, IL-6, CRP, and TNF-α compared to LZD monotherapy.
Conclusions:
- * Co-administration of hUMSCs significantly enhances the therapeutic efficacy of LZD in treating MRSA-induced pneumonia in a rabbit model.
- * The synergistic effect is characterized by improved clinical and pathological outcomes and a greater reduction in systemic inflammation.
- * This combination therapy represents a promising strategy for managing severe MRSA pneumonia.
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