期刊
RESPIRATORY RESEARCH
卷 15, 期 -, 页码 -出版社
BMC
DOI: 10.1186/s12931-014-0118-x
关键词
Elastase; Emphysema; Remodeling; Macrophage; Mesenchymal stromal cells
资金
- Centers of Excellence Program (PRONEX-FAPERJ)
- Brazilian Council for Scientific and Technological Development (CNPq)
- Carlos Chagas Filho Rio de Janeiro State Research Supporting Foundation (FAPERJ)
- Sao Paulo State Research Support Foundation (FAPESP)
- National Institute of Science and Technology of Drugs and Medicine (INCT-INOFAR)
- Coordination for the improvement of Higher Level Personnel (CAPES)
We sought to assess whether the effects of mesenchymal stromal cells (MSC) on lung inflammation and remodeling in experimental emphysema would differ according to MSC source and administration route. Emphysema was induced in C57BL/6 mice by intratracheal (IT) administration of porcine pancreatic elastase (0.1 UI) weekly for 1 month. After the last elastase instillation, saline or MSCs (1x10(5)), isolated from either mouse bone marrow (BM), adipose tissue (AD) or lung tissue (L), were administered intravenously (IV) or IT After 1 week, mice were euthanized. Regardless of administration route, MSCs from each source yielded: 1) decreased mean linear intercept, neutrophil infiltration, and cell apoptosis; 2) increased elastic fiber content; 3) reduced alveolar epithelial and endothelial cell damage; and 4) decreased keratinocyte-derived chemokine (KC, a mouse analog of interleukin-8) and transforming growth factor levels in lung tissue. In contrast with IV, IT MSC administration further reduced alveolar hyperinflation (EM MSC) and collagen fiber content (BM MSC and L MSC). Intravenous administration of BM and AD MSCs reduced the number of M1 macrophages and pulmonary hypertension on echocardiography, while increasing vascular endothelial growth factor. Only BM-MSCs (IV > IT) increased the number of M2 macrophages. In conclusion, different MSC sources and administration routes variably reduced elastase-induced lung damage, but IV administration of BM-MSCs resulted in better cardiovascular function and change of the macrophage phenotype from M1 to M2.
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