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Enhancing the Engraftment of Human Induced Pluripotent Stem Cell-derived Cardiomyocytes via a Transient Inhibition of Rho Kinase Activity
Published on: July 10, 2019
Combined treatment with mesenchymal stem cells and ROCK inhibitor Y-27632 ameliorates PM2.5-induced lung injury
He Jiang1, Lifang Jin2,3, ShanShan Tan2
1Center for General Practice Medicine, Department of Traditional Chinese Medicine, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, No. 158, Shangtang Road, Gongshu District, Hangzhou, Zhejiang 310014, China.
Abstract:
Particulate matter 2.5 μm (PM2.5) can directly enter the human respiratory tract and cause damage to lungs. Mesenchymal stem cells (MSCs) transplantation has emerged as a promising therapeutic strategy for ameliorating lung injury. Nonetheless, the lineage fate of recruited MSCs in the lung can be impacted by Rho-associated protein kinase 1 (ROCK) signaling. The current study investigated whether a combined treatment of MSCs with ROCK inhibitor Y-27632 offers enhanced therapeutic efficacy in addressing PM2.5-induced lung injury. The combined therapeutic efficacy was analyzed by wound healing assay, oxidative response and inflammatory factors in PM2.5-treated A549 cells. Besides, the combined MSCs and Y-27632 therapy was also analyzed by lung pathology, EMT response and inflammatory factors in PM2.5-treated mice. Combined MSCs and Y-27632 treatment more effectively restored wound healing ability and attenuated oxidative stress and inflammatory response in PM2.5-injured A549 cells than MSCs monotherapy. Immunohistochemical analysis result demonstrated that PM2.5 exposure altered markers related to epithelial-to-mesenchymal transition (EMT), such as E-cadherin, α-SMA and vimentin in lung tissue. Both MSCs monotherapy and combined MSCs and Y-27632 therapy restored lung injury by reducing lung pathology, oxidative stress, inflammatory response, and EMT process by inhibiting β-catenin pathway. However, the combined treatment proved more efficacious in mitigating PM2.5-induced lung injury. Although MSCs alleviated PM2.5-induced lung injury, the combined therapeutic efficacy of MSCs and Y-27632 offered a better treatment effect. This study offers valuable insights into the mechanisms of lung injury induced by PM2.5 and potential interventional treatments.
Insights
Combining mesenchymal stem cells (MSCs) with ROCK inhibitor Y-27632 enhances treatment for particulate matter 2.5 (PM2.5)-induced lung injury. This combined therapy offers superior efficacy in mitigating lung damage, inflammation, and oxidative stress compared to MSCs alone.
Area of Science:
- Pulmonary Medicine
- Regenerative Medicine
- Toxicology
Background:
- Particulate matter 2.5 (PM2.5) exposure causes lung injury.
- Mesenchymal stem cells (MSCs) show therapeutic potential for lung injury.
- Rho-associated protein kinase 1 (ROCK) signaling influences MSC function in the lungs.
Purpose of the Study:
- To investigate the enhanced therapeutic efficacy of combined MSCs and ROCK inhibitor Y-27632 for PM2.5-induced lung injury.
- To elucidate the underlying mechanisms of this combined therapy.
Main Methods:
- In vitro analysis using PM2.5-treated A549 cells (wound healing, oxidative stress, inflammatory factors).
- In vivo analysis using PM2.5-treated mice (lung pathology, epithelial-to-mesenchymal transition (EMT) markers, inflammatory factors).
- Immunohistochemical analysis of EMT markers (E-cadherin, α-SMA, vimentin) and β-catenin pathway.
Main Results:
- Combined MSCs and Y-27632 treatment significantly improved wound healing and reduced oxidative stress and inflammation in A549 cells compared to MSCs alone.
- PM2.5 exposure altered EMT markers in mouse lung tissue.
- Both MSC monotherapy and combined therapy reduced lung pathology, oxidative stress, inflammation, and EMT by inhibiting the β-catenin pathway.
- The combined MSCs and Y-27632 treatment demonstrated superior efficacy in mitigating PM2.5-induced lung injury.
Conclusions:
- Combined MSCs and Y-27632 therapy offers enhanced therapeutic benefits for PM2.5-induced lung injury.
- This approach effectively reduces inflammation, oxidative stress, and EMT.
- The findings provide valuable insights into PM2.5 lung injury mechanisms and potential interventions.
