Age related changes of the lung extracellular matrix stiffness and stem cell viability

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Background: Mesenchymal Stem Cells (MSCs) offer a new therapeutic approach for chronic and acute lung diseases. However, the effects of aging-derived ECM alterations on MSCs viability are not well elucidated. ObjectiveS: To study the ECM mechanical changes caused by aging in resting volume (RV) and physiologically inflated lungs and to test MSCs viability. Methods: Lungs were harvested from 4 young (6-month-old) and 8 aged (20-24-month-old) mice and subsequently inflated with 1:3 dilution of optimal cutting temperature (OCT) compound to reach functional residual capacity (FRC) or without inflation (RV). Lung cryosections (20 µm) were decellularized attached to a glass slide. The mechanical properties of the acellular samples were assessed by AFM. From each indentation curve, the viscosity and young’s modulus (E) were computed. The total amount of collagen was assessed. The acellular scaffolds were recellularized with MSCs and their viability was analyzed. Results: Under FCR conditions, the stiffness (E) and viscosity measured in decellularized lungs from old mice (0.70 ± 0.17kPa and 0.014 ± 0.002 kPa.s, respectively) were higher respect to that observed in young mice (0.43 ± 0.07kPa and 0.012 ± 0.001 kPa.s, respectively). However, no differences in the collagen content were found. Under RV conditions, no differences in stiffness nor viscosity were found. MSCs viability was reduced in RV respect to FRC conditions. Conclusions: Our results indicate that ECM becomes stiffer during aging. Also, our study shows that the mechanical properties of ECM and MSCs viability strongly depend on lung inflation suggesting that these studies should be done under physiologically inflated lungs.

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