Abnormalities in reparative function of lung-derived mesenchymal stromal cells in emphysema

Dennis Mlw Kruk, Marissa Wisman, Harold G de Bruin, Monique E Lodewijk, Danique J Hof, Theo Borghuis, Willeke F Daamen, Toin H van Kuppevelt, Wim Timens, Janette K Burgess, Nick H T Ten Hacken, Irene H Heijink*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Mesenchymal stromal cells (MSCs) may provide crucial support in the regeneration of destructed alveolar tissue (emphysema) in COPD. We hypothesized that lung-derived MSCs (LMSCs) from emphysema patients are hampered in their repair capacity, either intrinsically or due to their interaction with the damaged micro-environment. LMSCs were isolated from lung tissue of controls and severe emphysema patients, and characterized at baseline. Additionally, LMSCs were seeded onto control and emphysematous decellularized lung tissue scaffolds and assessed for deposition of extracellular matrix (ECM). We observed no differences in surface markers, differentiation/proliferation potential and expression of ECM genes between control- and COPD-derived LMSCs. Notably, COPD-derived LMSCs displayed lower expression of FGF10 and HGF mRNA, and HGF and decorin protein. When seeded on control decellularized lung tissue scaffolds, control and COPD-derived LMSCs showed no differences in engraftment, proliferation or survival within 2 weeks, with similar ability to deposit new matrix on the scaffolds. Moreover, LMSC numbers and ability to deposit new matrix was not compromised on emphysematous scaffolds. Collectively, our data show that LMSCs from COPD patients compared to controls show less expression of FGF10 mRNA, HGF mRNA and protein and decorin protein, while other features including the mRNA expression of various ECM molecules are unaffected. Furthermore, COPD-derived LMSCs are capable of engraftment, proliferation and functioning on native lung tissue scaffolds. The damaged, emphysematous micro-environment as such does not hamper the potential of LMSCs. Thus, specific intrinsic deficiencies in growth factor production by diseased LMSCs may contribute to impaired alveolar repair in emphysema.

Original languageEnglish
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
DOIs
Publication statusE-pub ahead of print - 2021

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