Abnormalities in reparative function of lung-derived mesenchymal stromal cells in emphysema.
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.
['Kruk|Dennis M L W|DMLW|', 'Wisman|Marissa|M|', 'Bruin|Harold G de|HG|', 'Lodewijk|Monique E|ME|', 'Hof|Danique J|DJ|', 'Borghuis|Theo|T|', 'Daamen|Willeke F|WF|0000-0003-3155-3030', 'van Kuppevelt|Toin H|TH|', 'Timens|Wim|W|0000-0002-4146-6363', 'Burgess|Janette K|JK|0000-0001-9868-9966', 'Ten Hacken|Nick H T|NHT|', 'Heijink|Irene H|IH|0000-0002-1260-8932']
D000328:Adult D000368:Aged D000369:Aged, 80 and over D016022:Case-Control Studies D002454:Cell Differentiation D049109:Cell Proliferation D002478:Cells, Cultured D005109:Extracellular Matrix D005260:Female D005786:Gene Expression Regulation D006801:Humans D008168:Lung D008297:Male D059630:Mesenchymal Stem Cells D008875:Middle Aged D029424:Pulmonary Disease, Chronic Obstructive D011656:Pulmonary Emphysema D054457:Tissue Scaffolds
emphysema MSCs extracellular matrix growth factors lung tissue repair