Effects of aging on the biomechanical properties of the lung extracellular matrix: dependence on tissular stretch

被引:5
作者
Ulldemolins, Anna [1 ]
Narciso, Maria [1 ,2 ]
Sanz-Fraile, Hector [1 ]
Otero, Jorge [1 ,3 ]
Farre, Ramon [1 ,3 ,4 ]
Gavara, Nuria [1 ,2 ]
Almendros, Isaac [1 ,3 ,4 ]
机构
[1] Univ Barcelona, Unitat Biofis & Bioengn, Fac Med & Ciencies Salut, Barcelona, Spain
[2] Barcelona Inst Sci & Technol, Inst Bioengn Catalonia IBEC, Barcelona, Spain
[3] CIBER Enfermedades Resp, Madrid, Spain
[4] Inst Invest Biomed August Pi I Sunyer, Barcelona, Spain
关键词
lung extracellular matrix; aging; lung volume; biomechanical properties; mesenchymal stromal cells; DECELLULARIZATION; AGE; STIFFNESS; MECHANICS; COLLAGEN; FIBROSIS; ELASTIN;
D O I
10.3389/fcell.2024.1381470
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Introduction: Aging induces functional and structural changes in the lung, characterized by a decline in elasticity and diminished pulmonary remodeling and regenerative capacity. Emerging evidence suggests that most biomechanical alterations in the lung result from changes in the composition of the lung extracellular matrix (ECM), potentially modulating the behavior of pulmonary cells and increasing the susceptibility to chronic lung diseases. Therefore, it is crucial to investigate the mechanical properties of the aged lung. This study aims to assess the mechanical alterations in the lung ECM due to aging at both residual (RV) and functional (FV) lung volumes and to evaluate their effects on the survival and proliferation of mesenchymal stromal cells (MSCs).Methods: The lungs from young (4-6-month-old) and aged (20-24-month-old) mice were inflated with optimal cutting temperature compound to reach FV or non-inflated (RV). ECM proteins laminin, collagen I and fibronectin were quantified by immunofluorescence and the mechanical properties of the decellularized lung sections were assessed using atomic force microscopy. To investigate whether changes in ECM composition by aging and/or mechanical properties at RV and FV volumes affects MSCs, their viability and proliferation were evaluated after 72 h.Results: Laminin presence was significantly reduced in aged mice compared to young mice, while fibronectin and collagen I were significantly increased in aged mice. In RV conditions, the acellular lungs from aged mice were significantly softer than from young mice. By contrast, in FV conditions, the aged lung ECM becomes stiffer than that of in young mice, revealing that strain hardening significantly depends on aging. Results after MSCs recellularization showed similar viability and proliferation rate in all conditions.Discussion: This data strongly suggests that biomechanical measurements, especially in aging models, should be carried out in physiomimetic conditions rather than following the conventional non-inflated lung (RV) approach. The use of decellularized lung scaffolds from aged and/or other lung disease murine/human models at physiomimetic conditions will help to better understand the potential role of mechanotransduction on the susceptibility and progression of chronic lung diseases, lung regeneration and cancer.
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页数:10
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共 44 条
[1]   Regenerative medicine in the treatment of idiopathic pulmonary fibrosis: current position [J].
Alvarez, Diana ;
Levine, Melanie ;
Rojas, Mauricio .
STEM CELLS AND CLONING-ADVANCES AND APPLICATIONS, 2015, 8 :61-65
[2]   The effects of storage and sterilization on de-cellularized and re-cellularized whole lung [J].
Bonenfant, Nicholas R. ;
Sokocevic, Dino ;
Wagner, Darcy E. ;
Borg, Zachary D. ;
Lathrop, Melissa J. ;
Lam, Ying Wai ;
Deng, Bin ;
DeSarno, Michael J. ;
Ashikaga, Taka ;
Loi, Roberto ;
Weiss, Daniel J. .
BIOMATERIALS, 2013, 34 (13) :3231-3245
[3]   Remodelling the extracellular matrix in development and disease [J].
Bonnans, Caroline ;
Chou, Jonathan ;
Werb, Zena .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2014, 15 (12) :786-801
[4]   ARDS: challenges in patient care and frontiers in research [J].
Bos, Lieuwe D. ;
Martin-Loeches, Ignacio ;
Schultz, Marcus J. .
EUROPEAN RESPIRATORY REVIEW, 2018, 27 (147)
[5]   Chronic lung diseases: entangled in extracellular matrix [J].
Burgess, Janette K. ;
Harmsen, Martin C. .
EUROPEAN RESPIRATORY REVIEW, 2022, 31 (163)
[6]   The instructive extracellular matrix of the lung: basic composition and alterations in chronic lung disease [J].
Burgstaller, Gerald ;
Oehrle, Bettina ;
Gerckens, Michael ;
White, Eric S. ;
Schiller, Herbert B. ;
Eickelberg, Oliver .
EUROPEAN RESPIRATORY JOURNAL, 2017, 50 (01)
[7]   Aging and Lung Disease [J].
Cho, Soo Jung ;
Stout-Delgado, Heather W. .
ANNUAL REVIEW OF PHYSIOLOGY, VOL 82, 2020, 82 :433-459
[8]   Aging-related changes in respiratory system mechanics and morphometry in mice [J].
Elliott, Jonathan E. ;
Mantilla, Carlos B. ;
Pabelick, Christina M. ;
Roden, Anja C. ;
Sieck, Gary C. .
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, 2016, 311 (01) :L167-L176
[9]   Abnormal Lung Aging in Chronic Obstructive Pulmonary Disease and Idiopathic Pulmonary Fibrosis [J].
Faner, Rosa ;
Rojas, Mauricio ;
MacNee, William ;
Agusti, Alvar .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2012, 186 (04) :306-313
[10]   Decreased Laminin Expression by Human Lung Epithelial Cells and Fibroblasts Cultured in Acellular Lung Scaffolds from Aged Mice [J].
Godin, Lindsay M. ;
Sandri, Brian J. ;
Wagner, Darcy E. ;
Meyer, Carolyn M. ;
Price, Andrew P. ;
Akinnola, Ifeolu ;
Weiss, Daniel J. ;
Panoskaltsis-Mortari, Angela .
PLOS ONE, 2016, 11 (03)