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

Abstract

Mesenchymal stromal cells (MSCs) may provide crucial support in the regeneration of destructed alveolar tissue (emphysema) in chronic obstructive pulmonary disease (COPD). We hypothesized that lung-derived MSCs (LMSCs) from patients with emphysema are hampered in their repair capacity, either intrinsically or due to their interaction with the damaged microenvironment. LMSCs were isolated from the lung tissue of controls and patients with severe emphysema and characterized at baseline. In addition, 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 messenger RNA (mRNA) and hepatocyte growth factor (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  wk, with similar ability to deposit new matrix on the scaffolds. Moreover, LMSC numbers and the ability to deposit new matrix were not compromised on emphysematous scaffolds. Collectively, our data show that LMSCs from patients with COPD compared with controls show less expression of FGF10 mRNA, HGF mRNA and protein, and decorin protein, whereas 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 microenvironment 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.

• Authors: Dennis M L W 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
• Journal: American journal of physiology. Lung cellular and molecular physiology (Am J Physiol Lung Cell Mol Physiol) Vol. 320 Issue 5 Pg. L832-L844 (05 01 2021) ISSN: 1522-1504 [Electronic] United States
• PMID: 33656381 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Topics

• Adult
• Aged
• Aged, 80 and over
• Case-Control Studies
• Cell Differentiation
• Cell Proliferation
• Cells, Cultured
• Extracellular Matrix (metabolism, pathology)
• Female
• Gene Expression Regulation
• Humans
• Lung (metabolism, pathology)
• Male
• Mesenchymal Stem Cells (metabolism, pathology)
• Middle Aged
• Pulmonary Disease, Chronic Obstructive (metabolism, pathology)
• Pulmonary Emphysema (metabolism, pathology)
• Tissue Scaffolds (chemistry)