Nestin reveals progenitor cells in pulmonary vascular wall

Vascular smooth muscle cells (VSMCs) and pericytes (PCs), distinguished by the expression of neuronal stem cell marker “Nestin”, may represent stem cell-like progenitor cells for tissues in various organs. In one of our previous studies, we found that nestin-expressing VSMCs and PCs in testicular blood vessels are the progenitors of testosterone producing Leydig cells.

To analyze the expression pattern of nestin and its role as marker for proliferating progenitor cells in the lung, nestin expression and localization was investigated during postnatal development in nestin-GFP mice. To investigate nestin-expression during vascular remodelling, samples from two models of pulmonary hypertension [monocrotaline (MCT) rat model and hypoxic mouse model] as well as human samples from patients of PH were analyzed. Nestin data was compared with expression of proliferation markers (PCNA, Ki67) and PDGF receptors.

Nestin was found in a subpopulation of VSMCs in lung vasculature. As compared to adult normoxic controls significantly higher nestin-expression was observed in pulmonary vasculature of postnatal tissues and in adult lungs between day 3–7 of hypoxic exposure but not at later time points when PH became evident. Nestin up-regulation correlated well with an increase of cell proliferation. In hypoxic lungs peak of phosphorylated (activated) PDGF receptor-ß correlated with nestin one.

Increase of nestin-immunoreactive VSMCs was also found in MCT rat and human lung samples. In these samples, in large and medium sized arteries, additional nestin was found in progenitor cells in so-called vasculogenic zone at the border of media and adventitia.

Certain vascular wall cells capable of proliferation could be identified by nestin expression in lungs and may be used as prognostic marker and new target for therapeutic interventions of diseases like pulmonary hypertension.