1. Mesenchymal stem/stromal cells stably transduced with an inhibitor of CC chemokine ligand 2 ameliorate bronchopulmonary dysplasia and pulmonary hypertension
- Author
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Toshihiko Suzuki, Atsuto Onoda, Hidenori Yamamoto, Masahiro Hayakawa, Yuma Kitase, Takayuki Nakayama, Yoshiyuki Takahashi, Yuichiro Sugiyama, Shigeki Saito, Taichi Kato, Yoshiaki Sato, Kazuto Ueda, and Haruka Mimatsu
- Subjects
Male ,0301 basic medicine ,Cancer Research ,Stromal cell ,Receptors, CCR2 ,Hypertension, Pulmonary ,Immunology ,Vascular Remodeling ,CCL2 ,Lung injury ,Mesenchymal Stem Cell Transplantation ,Transfection ,Viral vector ,03 medical and health sciences ,0302 clinical medicine ,Transduction, Genetic ,mental disorders ,Animals ,Humans ,Immunology and Allergy ,Medicine ,Macrophage ,Rats, Wistar ,Chemokine CCL2 ,Genetics (clinical) ,Bronchopulmonary Dysplasia ,Transplantation ,business.industry ,Macrophages ,Mesenchymal stem cell ,Cell Biology ,Macrophage Activation ,medicine.disease ,Pulmonary hypertension ,Rats ,Disease Models, Animal ,HEK293 Cells ,030104 developmental biology ,Oncology ,Bronchopulmonary dysplasia ,030220 oncology & carcinogenesis ,Cancer research ,Female ,Mutant Proteins ,business - Abstract
Perinatal bronchopulmonary dysplasia (BPD) is defined as lung injury in preterm infants caused by various factors, resulting in serious respiratory dysfunction and high mortality. The administration of mesenchymal stem/stromal cells (MSCs) to treat/prevent BPD has proven to have certain therapeutic effects. However, MSCs can only weakly regulate macrophage function, which is strongly involved in the development of BPD. 7ND-MSCs are MSCs transfected with 7ND, a truncated version of CC chemokine ligand 2 (CCL2) that promotes macrophage activation, using a lentiviral vector. In the present study, we show in a BPD rat model that 7ND-MSC administration, but not MSCs alone, ameliorated the impaired alveolarization evaluated by volume density and surface area in the lung tissue, as well as pulmonary artery remodeling and pulmonary hypertension induced by BPD. In addition, 7ND-MSCs, but not MSCs alone, reduced M1 macrophages and the messenger RNA expressions of interleukin-6 and CCL2 in the lung tissue. Thus, the present study showed the treatment effect of 7ND-MSCs in a BPD rat model, which was more effective than that of MSCs alone.
- Published
- 2020