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Therapeutic benefits of young, but not old, adipose-derived mesenchymal stem cells in a chronic mouse model of bleomycin-induced pulmonary fibrosis.
Transl Res 2015; 166(6):554-67TR

Abstract

The observation that pulmonary inflammatory lesions and bleomycin (BLM)-induced pulmonary fibrosis spontaneously resolve in young mice, whereas remaining irreversible in aged mice suggests that impairment of pulmonary regeneration and repair is associated with aging. Because mesenchymal stem cells (MSCs) may promote repair after injury, we postulated that differences in MSCs from aged mice may underlie postinjury fibrosis in aging. The potential for young-donor MSCs to inhibit BLM-induced pulmonary fibrosis in aged male mice (>22 months) has not been studied. Adipose-derived MSCs (ASCs) from young (4 months) and old (22 months) male mice were infused 1 day after intratracheal BLM administration. At 21-day sacrifice, aged BLM mice demonstrated lung fibrosis by Ashcroft score, collagen content, and α(v)-integrin messenger RNA (mRNA) expression. Lung tissue from aged BLM mice receiving young ASCs exhibited decreased fibrosis, matrix metalloproteinase (MMP)-2 activity, oxidative stress, and markers of apoptosis vs BLM controls. Lung mRNA expression of tumor necrosis factor-alpha was also decreased in aged BLM mice receiving young-donor ASCs vs BLM controls. In contrast, old-donor ASC treatment in aged BLM mice did not reduce fibrosis and related markers. On examination of the cells, young-donor ASCs had decreased mRNA expression of MMP-2, insulin-like growth factor (IGF) receptor, and protein kinase B (AKT) activation compared with old-donor ASCs. These results show that the BLM-induced pulmonary fibrosis in aged mice could be blocked by young-donor ASCs and that the mechanisms involve changes in collagen turnover and markers of inflammation.

Authors+Show Affiliations

Department of Surgery, Leonard M. Miller School of Medicine, University of Miami, Miami, Fla.Department of Surgery, Leonard M. Miller School of Medicine, University of Miami, Miami, Fla.Department of Surgery, Leonard M. Miller School of Medicine, University of Miami, Miami, Fla.Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Department of Medicine, Leonard M. Miller School of Medicine, University of Miami, Miami, Fla.Department of Surgery, Leonard M. Miller School of Medicine, University of Miami, Miami, Fla.Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Department of Medicine, Leonard M. Miller School of Medicine, University of Miami, Miami, Fla.Department of Surgery, Leonard M. Miller School of Medicine, University of Miami, Miami, Fla.Division of Pediatric Pulmonology, Department of Pediatrics, Leonard M. Miller School of Medicine, University of Miami, Miami, Fla.Department of Medicine, Herbert Wertheim College of Medicine, Florida International University, Miami, Fla.Department of Surgery, Leonard M. Miller School of Medicine, University of Miami, Miami, Fla.Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY.Department of Surgery, Leonard M. Miller School of Medicine, University of Miami, Miami, Fla; Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Department of Medicine, Leonard M. Miller School of Medicine, University of Miami, Miami, Fla; Division of Pediatric Pulmonology, Department of Pediatrics, Leonard M. Miller School of Medicine, University of Miami, Miami, Fla. Electronic address: mglassbe@med.miami.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

26432923

Citation

Tashiro, Jun, et al. "Therapeutic Benefits of Young, but Not Old, Adipose-derived Mesenchymal Stem Cells in a Chronic Mouse Model of Bleomycin-induced Pulmonary Fibrosis." Translational Research : the Journal of Laboratory and Clinical Medicine, vol. 166, no. 6, 2015, pp. 554-67.
Tashiro J, Elliot SJ, Gerth DJ, et al. Therapeutic benefits of young, but not old, adipose-derived mesenchymal stem cells in a chronic mouse model of bleomycin-induced pulmonary fibrosis. Transl Res. 2015;166(6):554-67.
Tashiro, J., Elliot, S. J., Gerth, D. J., Xia, X., Pereira-Simon, S., Choi, R., ... Glassberg, M. K. (2015). Therapeutic benefits of young, but not old, adipose-derived mesenchymal stem cells in a chronic mouse model of bleomycin-induced pulmonary fibrosis. Translational Research : the Journal of Laboratory and Clinical Medicine, 166(6), pp. 554-67. doi:10.1016/j.trsl.2015.09.004.
Tashiro J, et al. Therapeutic Benefits of Young, but Not Old, Adipose-derived Mesenchymal Stem Cells in a Chronic Mouse Model of Bleomycin-induced Pulmonary Fibrosis. Transl Res. 2015;166(6):554-67. PubMed PMID: 26432923.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Therapeutic benefits of young, but not old, adipose-derived mesenchymal stem cells in a chronic mouse model of bleomycin-induced pulmonary fibrosis. AU - Tashiro,Jun, AU - Elliot,Sharon J, AU - Gerth,David J, AU - Xia,Xiaomei, AU - Pereira-Simon,Simone, AU - Choi,Rhea, AU - Catanuto,Paola, AU - Shahzeidi,Shahriar, AU - Toonkel,Rebecca L, AU - Shah,Rahil H, AU - El Salem,Fadi, AU - Glassberg,Marilyn K, Y1 - 2015/09/18/ PY - 2015/05/05/received PY - 2015/09/10/revised PY - 2015/09/10/accepted PY - 2015/10/4/entrez PY - 2015/10/4/pubmed PY - 2016/3/22/medline SP - 554 EP - 67 JF - Translational research : the journal of laboratory and clinical medicine JO - Transl Res VL - 166 IS - 6 N2 - The observation that pulmonary inflammatory lesions and bleomycin (BLM)-induced pulmonary fibrosis spontaneously resolve in young mice, whereas remaining irreversible in aged mice suggests that impairment of pulmonary regeneration and repair is associated with aging. Because mesenchymal stem cells (MSCs) may promote repair after injury, we postulated that differences in MSCs from aged mice may underlie postinjury fibrosis in aging. The potential for young-donor MSCs to inhibit BLM-induced pulmonary fibrosis in aged male mice (>22 months) has not been studied. Adipose-derived MSCs (ASCs) from young (4 months) and old (22 months) male mice were infused 1 day after intratracheal BLM administration. At 21-day sacrifice, aged BLM mice demonstrated lung fibrosis by Ashcroft score, collagen content, and α(v)-integrin messenger RNA (mRNA) expression. Lung tissue from aged BLM mice receiving young ASCs exhibited decreased fibrosis, matrix metalloproteinase (MMP)-2 activity, oxidative stress, and markers of apoptosis vs BLM controls. Lung mRNA expression of tumor necrosis factor-alpha was also decreased in aged BLM mice receiving young-donor ASCs vs BLM controls. In contrast, old-donor ASC treatment in aged BLM mice did not reduce fibrosis and related markers. On examination of the cells, young-donor ASCs had decreased mRNA expression of MMP-2, insulin-like growth factor (IGF) receptor, and protein kinase B (AKT) activation compared with old-donor ASCs. These results show that the BLM-induced pulmonary fibrosis in aged mice could be blocked by young-donor ASCs and that the mechanisms involve changes in collagen turnover and markers of inflammation. SN - 1878-1810 UR - https://www.unboundmedicine.com/medline/citation/26432923/Therapeutic_benefits_of_young_but_not_old_adipose_derived_mesenchymal_stem_cells_in_a_chronic_mouse_model_of_bleomycin_induced_pulmonary_fibrosis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1931-5244(15)00308-4 DB - PRIME DP - Unbound Medicine ER -