Yu-Kun Yang1,2,3,4, Ye Li1,2,3,4, Yan-Ying Wang1,2,3, Guang-Ping Ruan1,2,3, Chuan Tian1,2,3, Qiang Wang1,2,3, Huan-Yu He4, Gao-Hong Zhu5, Dong Fang5, Mao Wang5, Xiang-Qing Zhu6,7,8,9, Xing-Hua Pan10,11,12,13. 1. Kunming Key Laboratory of Stem Cell and Regenerative Medicine, 920th Hospital of the PLA Joint Logistics Support Force, Kunming, 650032, Yunnan Province, China. 2. Stem Cells and Immune Cells Biomedical Techniques Integrated Engineering Laboratory of State and Regions, 920th Hospital of the PLA Joint Logistics Support Force, Kunming, 650032, Yunnan Province, China. 3. Cell Therapy Technology Transfer Medical Key Laboratory of Yunnan Province, Kunming, Yunnan Province, China. 4. Kunming Medical University, Kunming, Yunnan Province, China. 5. Department of Nuclear Medicine, the First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan Province, China. 6. Kunming Key Laboratory of Stem Cell and Regenerative Medicine, 920th Hospital of the PLA Joint Logistics Support Force, Kunming, 650032, Yunnan Province, China. qing1021zhu@163.com. 7. Stem Cells and Immune Cells Biomedical Techniques Integrated Engineering Laboratory of State and Regions, 920th Hospital of the PLA Joint Logistics Support Force, Kunming, 650032, Yunnan Province, China. qing1021zhu@163.com. 8. Cell Therapy Technology Transfer Medical Key Laboratory of Yunnan Province, Kunming, Yunnan Province, China. qing1021zhu@163.com. 9. Kunming Medical University, Kunming, Yunnan Province, China. qing1021zhu@163.com. 10. Kunming Key Laboratory of Stem Cell and Regenerative Medicine, 920th Hospital of the PLA Joint Logistics Support Force, Kunming, 650032, Yunnan Province, China. xinghuapan@aliyun.com. 11. Stem Cells and Immune Cells Biomedical Techniques Integrated Engineering Laboratory of State and Regions, 920th Hospital of the PLA Joint Logistics Support Force, Kunming, 650032, Yunnan Province, China. xinghuapan@aliyun.com. 12. Cell Therapy Technology Transfer Medical Key Laboratory of Yunnan Province, Kunming, Yunnan Province, China. xinghuapan@aliyun.com. 13. Kunming Medical University, Kunming, Yunnan Province, China. xinghuapan@aliyun.com.
Abstract
BACKGROUND: Age-associated lung tissue degeneration is a risk factor for lung injury and exacerbated lung disease. It is also the main risk factor for chronic lung diseases (such as COPD, idiopathic pulmonary fibrosis, cancer, among others). So, it is particularly important to find new anti-aging treatments. METHODS: We systematically screened and evaluated elderly senile multiple organ dysfunction macaque models to determine whether BMMSCs inhibited lung tissue degeneration. RESULTS: The average alveolar area, mean linear intercept (MLI), and fibrosis area in the elderly macaque models were significantly larger than in young rhesus monkeys (p < 0.05), while the capillary density around the alveoli was significantly low than in young macaque models (p < 0.05). Intravenous infusion of BMMSCs reduced the degree of pulmonary fibrosis, increased the density of capillaries around the alveoli (p < 0.05), and the number of type II alveolar epithelium in elderly macaques (p < 0.05). In addition, the infusion reduced lung tissue ROS levels, systemic and lung tissue inflammatory levels, and Treg cell ratio in elderly macaque models (p < 0.05). Indirect co-cultivation revealed that BMMSCs suppressed the expression of senescence-associated genes, ROS levels, apoptosis rate of aging type II alveolar epithelial cells (A549 cells), and enhanced their proliferation (p < 0.05). CONCLUSIONS: BMMSC treatment inhibited age-associated lung tissue degeneration.
BACKGROUND: Age-associated lung tissue degeneration is a risk factor for lung injury and exacerbated lung disease. It is also the main risk factor for chronic lung diseases (such as COPD, idiopathic pulmonary fibrosis, cancer, among others). So, it is particularly important to find new anti-aging treatments. METHODS: We systematically screened and evaluated elderly senile multiple organ dysfunction macaque models to determine whether BMMSCs inhibited lung tissue degeneration. RESULTS: The average alveolar area, mean linear intercept (MLI), and fibrosis area in the elderly macaque models were significantly larger than in young rhesus monkeys (p < 0.05), while the capillary density around the alveoli was significantly low than in young macaque models (p < 0.05). Intravenous infusion of BMMSCs reduced the degree of pulmonary fibrosis, increased the density of capillaries around the alveoli (p < 0.05), and the number of type II alveolar epithelium in elderly macaques (p < 0.05). In addition, the infusion reduced lung tissue ROS levels, systemic and lung tissue inflammatory levels, and Treg cell ratio in elderly macaque models (p < 0.05). Indirect co-cultivation revealed that BMMSCs suppressed the expression of senescence-associated genes, ROS levels, apoptosis rate of aging type II alveolar epithelial cells (A549 cells), and enhanced their proliferation (p < 0.05). CONCLUSIONS: BMMSC treatment inhibited age-associated lung tissue degeneration.
Entities:
Keywords:
BMMSCs; Lung degeneration; Macaque; Type II alveolar epithelial cells
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