Page 42 - MemoriaES-Eng

RESEARCH PROGRAMMES

myofibroblasts. In pathologic conditions, some glycoprotein ECM components remain in-

creased, collagen I and III are not degraded; myofibroblasts evade apoptosis and de-
velop dysfunctional repair mechanisms. The contributions of the different environmental

alterations during dysfunctional repair to tissue scar are likely to depend on the particular

disease and organ, and overall remain poorly understood. Our group has recently dem-
onstratedabnormallyhighlevelsof ECMcomponentsinIPFlungsthatareimplicatedin

tissue remodelling (cell adhesion, fibroblast migration). Myofibroblasts are interstitial key
effector cells in pulmonary fibrosis that can be derived from resident fibroblasts undergo-

ing fibroblast-to-myofibroblast transformation (FMT), alveolar epithelial-to-mesenchymal

transition (EMT), mesenchymal stem cells (MSCs) or even endothelial cells (EnMT). FMT
is characterized by a dramatic increase in wound ECM components including collagens

and glycoproteins. Extracellular microenvironment can regulate FMT and EMT. Based on

these observations it is tempting to speculate that there is a positive feedback
loop between cell and extracellular-dependent microenvironment. Although EnMT

has been less studied, it has been included as one of the different cellular process charac-
teristics in the remodelling of pulmonary hypertension (PH)-associated IPF, together with

endothelial dysfunction. PH in IPF portends a poor prognosis.

Advanced 3D cell culture model for the study of cell-ECM protein interactions.

Traditional approaches to study IPF include conventional 2D culture systems, which lack

essential components of the original tissue, and animal models that contain the full com-
plexity of the tissue but lack the irreversible behaviour of IPF. There is wide evidence

that cells grown in 3D cultures with appropriate ECM components retain many of their
phenotypic characteristics, thereby behaving more closely to their in vivo conditions. Our

programme is working in a 3D culture model.

1. To study glycoprotein effect on primary human lung alveolar and mesen-
Aims and
chymal cells (migration, metabolism and differentiation) and the regulation of its
objectives
synthesis in fibro-myofibroblasts .

2. To evaluate the differences in cell behaviour and experimental results de-

pending on telomere length and telomerase gene mutations.

3. To identify, characterize and assess, in vitro, the functional status and the

regenerative/reparative capacity of both hLRSC, including lung-hMSCs and
BM-hMSCs, from patients with IPF, compared to those obtained from subjects with

normal lung function.

4. Compare in these cells released factors related to signalling pathways that

induce proliferative and fibrogenic features of pulmonary target cells.

5. To investigate the remodelling of those vascular structural cells from pa-
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tients with PH complicating IPF, and its possible regulation through some in- 20
hibitors.
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6. To study aquoporin system in lung fibrosis and its modulation depending on PO
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the cell type and environmental growing conditions.
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