Comparison Between Bone Marrow Mesenchymal Stromal Cells (BM-MSC) and Lung Mesenchymal Stromal Cells (Lung-MSC) For Epithelial Regeneration

Developing a therapeutic strategy for lung regeneration still remains complex. Stem cell-based therapeutical approaches have been suggested as a potential tool; among them, human mesenchymal stromal cells (MSC) possess some promising features to this aim. MSC are stem cells residing in many tissue, i.e. bone marrow (BM), adipose tissue, cord blood, lung, etc., and they are capable of differentiating into different cell types of mesodermal origin, such as fat, bone and cartilage.

To assess MSC epithelial differentiation potential, through a partially known process called Mesenchymal to Epithelial Transition (MET), MSC were collected from bone (BM) aspirates and lung biopsies after informed consent. MSC were characterized by immunophenotyping and clonogenicity assay. MSC mesodermal differentiation potential was assessed by testing their ability to differentiate into adipocytes, osteoblasts and chondrocytes. MSCs at different culture passages were induced to acquire the epithelial phenotype by culturing in presence of retinoic acid. The epithelial differentiation was checked by quantitative RT-PCR, immunofluorescence and a functional assay based on the Trans Epithelial Electrical Resistance Measurement (TEER).

In presence of retinoic acid, MSC from BM and, mostly, lung upregulated a panel of general epithelial genes (cytokeratin 18, occludin, tight junction protein and claudin) and downregulated some specific mesenchymal markers (smooth muscle actin, snail2, vimentin, THY1), as detected by quantitative RT-PCR. Immunofluorescence confirmed the presence of E-cadherin4, occludin and cytokeratin 18 in a small number of cells (about 0,2 %). Trans Epithelial Electrical Resistance (TEER) measurement confirmed that MSC can acquire in vitro partial epithelial polarization after retinoic acid treatment.

These data show that MSC can be induced to differentate into cells resembling some morphological, phenotypical and functional properties of epithelial cells. BM-MSC are less prone to acquire an epithelial phenotype as compared to hLung-MSC. Additional in vivo studies on mouse model with lung damage are in progress.