The anti-inflammatory effects of mesenchymal stem cells attenuate diffuse pulmonary hemorrhage
Yajin Guan1,2, Qianqing Chen3,4, Jiahuan Xu3,4
1School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China.
Abstract:
There are few effective treatment options for diffuse pulmonary hemorrhage (DPH). We aimed to elucidate the therapeutic role and underlying mechanisms of mesenchymal stem cells (MSCs) and MSC-derived extracellular vesicles (MSC-EVs) in DPH. Therapeutic effects of MSCs/MSC-EVs in pristane-induced DPH mice were evaluated via pulmonary function testing and histopathology. Transcriptome sequencing analyzed differentially expressed genes in control, DPH, and MSC groups. The proportion of macrophage polarization was evaluated in vivo and in vitro via fluorescence-activated cell sorting in control, DPH, MSC, MSC-EV inhalation, and MSC-EV intravenous groups. Intraperitoneal injection of pristane induced diffuse alveolar hemorrhage, early fibrosis, and inflammation in C57BL/6 mice. Monocytes were depleted in the peripheral blood in DPH mice and MSCs were recruited to the lungs, resulting in significantly attenuated diffuse alveolar hemorrhage and suppressed immunological response. This was more effective in the hyperacute hemorrhage phase than the early inflammatory phase. An MSC treatment-mediated anti-inflammatory effect was observed in DPH mice. Furthermore, MSC-EVs inhalation or tail-vein injection could effectively reduce DPH injury. MSCs could suppress macrophage M1 polarization in DPH in vivo and in vitro. MSCs displayed significant therapeutic effects in pristane-induced DPH, which may be a promising cell-free therapeutic approach.
Insights
Mesenchymal stem cells (MSCs) and their extracellular vesicles (MSC-EVs) show promise for treating diffuse pulmonary hemorrhage (DPH). MSCs reduce inflammation and injury in DPH models, offering a potential cell-free therapy.
Area of Science:
- Regenerative Medicine
- Pulmonary Immunology
- Cell Therapy
Background:
- Diffuse pulmonary hemorrhage (DPH) has limited effective treatment options.
- Understanding the therapeutic mechanisms of mesenchymal stem cells (MSCs) and MSC-derived extracellular vesicles (MSC-EVs) is crucial for DPH management.
Purpose of the Study:
- To investigate the therapeutic potential and underlying mechanisms of MSCs and MSC-EVs in a mouse model of DPH.
- To evaluate the impact of MSCs and MSC-EVs on pulmonary function, inflammation, and macrophage polarization in DPH.
Main Methods:
- Pristane-induced DPH model in C57BL/6 mice.
- Evaluation of pulmonary function, histopathology, and gene expression.
- Assessment of macrophage polarization using fluorescence-activated cell sorting (FACS) in vivo and in vitro.
- Administration of MSCs and MSC-EVs via different routes (intraperitoneal, inhalation, intravenous).
Main Results:
- MSCs attenuated diffuse alveolar hemorrhage, fibrosis, and inflammation in DPH mice.
- MSC treatment suppressed M1 macrophage polarization, indicating an anti-inflammatory effect.
- MSC-derived extracellular vesicles (MSC-EVs) administered via inhalation or intravenous injection also reduced DPH injury.
- Therapeutic effects were more pronounced during the hyperacute hemorrhage phase compared to the early inflammatory phase.
Conclusions:
- MSCs demonstrate significant therapeutic effects in a pristane-induced DPH model.
- MSC-EVs represent a promising cell-free therapeutic strategy for DPH.
- Targeting macrophage polarization is a key mechanism underlying MSC-mediated DPH treatment.
Related Concept Videos
01:19Mesenchymal Stem Cells
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