Title |
Senescence of bone marrow-derived mesenchymal stem cells from patients with idiopathic pulmonary fibrosis
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Published in |
Stem Cell Research & Therapy, September 2018
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DOI | 10.1186/s13287-018-0970-6 |
Pubmed ID | |
Authors |
Nayra Cárdenes, Diana Álvarez, Jacobo Sellarés, Yating Peng, Catherine Corey, Sophie Wecht, Seyed Mehdi Nouraie, Swaroop Shanker, John Sembrat, Marta Bueno, Sruti Shiva, Ana L. Mora, Mauricio Rojas |
Abstract |
Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease for which age is the most important risk factor. Different mechanisms associated with aging, including stem cell dysfunction, have been described to participate in the pathophysiology of IPF. We observed an extrapulmonary effect associated with IPF: increase in cell senescence of bone marrow-derived mesenchymal stem cells (B-MSCs). B-MSCs were obtained from vertebral bodies procured from IPF patients and age-matched normal controls. Cell senescence was determined by cell proliferation and expression of markers of cell senescence p16INK4A, p21, and β-galactosidase activity. Mitochondrial function and DNA damage were measured. Paracrine induction of senescence and profibrotic responses were analyzed in vitro using human lung fibroblasts. The reparative capacity of B-MSCs was examined in vivo using the bleomycin-induced lung fibrosis model. In our study, we demonstrate for the first time that B-MSCs from IPF patients are senescent with significant differences in mitochondrial function, with accumulation of DNA damage resulting in defects in critical cell functions when compared with age-matched controls. Senescent IPF B-MSCs have the capability of paracrine senescence by inducing senescence in normal-aged fibroblasts, suggesting a possible link between senescent B-MSCs and the late onset of the disease. IPF B-MSCs also showed a diminished capacity to migrate and were less effective in preventing fibrotic changes observed in mice after bleomycin-induced injury, increasing illness severity and proinflammatory responses. We describe extrapulmonary alterations in B-MSCs from IPF patients. The consequences of having senescent B-MSCs are not completely understood, but the decrease in their ability to respond to normal activation and the risk of having a negative impact on the local niche by inducing inflammation and senescence in the neighboring cells suggests a new link between B-MSC and the onset of the disease. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United States | 5 | 26% |
Spain | 5 | 26% |
Canada | 1 | 5% |
Switzerland | 1 | 5% |
Unknown | 7 | 37% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 13 | 68% |
Practitioners (doctors, other healthcare professionals) | 3 | 16% |
Scientists | 2 | 11% |
Science communicators (journalists, bloggers, editors) | 1 | 5% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 73 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 11 | 15% |
Student > Master | 10 | 14% |
Student > Bachelor | 8 | 11% |
Student > Doctoral Student | 5 | 7% |
Professor | 5 | 7% |
Other | 9 | 12% |
Unknown | 25 | 34% |
Readers by discipline | Count | As % |
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Biochemistry, Genetics and Molecular Biology | 14 | 19% |
Medicine and Dentistry | 7 | 10% |
Pharmacology, Toxicology and Pharmaceutical Science | 5 | 7% |
Agricultural and Biological Sciences | 4 | 5% |
Immunology and Microbiology | 4 | 5% |
Other | 11 | 15% |
Unknown | 28 | 38% |