Mesenchymal stromal cells of the lung: Can we finally tell them apart

Cellular and molecular mechanisms (English)

Dennis Kruk
University Medical Center Groningen, Medical Biology & Pathology
In the adult lung, resident mesenchymal progenitors can replenish stromal cell populations. Mesenchymal progenitors that have clonogenic potential and can differentiate into multiple mesenchymal lineages in vitro are referred to as mesenchymal stromal(MSCs). Studying these specific lung mesenchymal progenitors is challenging, as many surface markers to distinguish mesenchymal cell types, e.g. lung MSCs (LMSCs) and lung fibroblasts (LFs), are not unique. We hypothesised that, being long-living, LMSCs can be distinguished from LFs by lower expression of senescence markers.

LMSCs (n=8) and LFs (n=8) were isolated from transplanted lung of severe COPD patients or from resection lung tissue collected as far away from the tumor as possible. Both cell types were generated using an explant method, whereLMSCs wereisolated by trypsin digestion and outgrowth on fibronectin coated-wells , while LFs were explanted directly onto plastic. Cells were expanded for 5 passages and RNA was collected. mRNA expression of senescence markers p21 and p16 was measured and senescence-associated β-Galactosidase (SA-β-gal) activity was assessed by staining.

LMSCs had significantly lower mRNA expression of p21 and to a lesser extent p16 compared to LFs. These differences were consistent regardless of disease status. In line with the lower expression of senescence markers in LMSCs, only ~0.03% of the LMSC cultured were SA-β-Gal positive.

Collectively, these results indicate that the expression of senescence markers is lower in LMSCs than in LFs and especially p21 can be used to distinguish LMSCs from LFs. The relatively low expression of senescence markers indicates that LMSCs may possess higher potential to self-renew than other stromal lung cell types, being more resistant to exhaustion.
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