Microenvironments for New Therapies

ABOUT 

The Microenvironments for NewTherapies group is constituted by complementary teams led by independent PIs, structured around the concept that microenvironments play a key role in cell behavior.

Our research activities have been designed to systematically dissect the cellular and non-cellular (extracellular matrix/ECM) microenvironment elements that contribute to reestablish homeostasis upon disease and/or injury. Envisaging clinical applications, our Group aims to bioengineer microenvironments in an effort to modulate host response, leading to tissue regeneration/functional restoration. The Group is focusing on different disease model-systems, i.e., osteoarticular conditions, intervertebral disc (IVD) degeneration, hemato-cardiovascular pathologies and the contribution of immune cells to cancer cell invasion and metastasis.

Research teams

1. Bioengineered microenvironments for repair/regeneration (PI: MA Barbosa)

2. Stem-cell microenvironments in repair/regeneration (PI: P Pinto-do-Ó)

3. Microenvironments in cancer cell invasion and metastasis (PI: MJ Oliveira)

Key words: Repair/regeneration and cancer microenvironments; Cell-biomaterial, cell-ECM, cell-cell Interactions; Stem/progenitor cells; Inflammation in repair/regeneration.

PAST RESEARCH

Bioengineered microenvironments for repair/regeneration

Biomaterials incorporating inflammatory signals were evaluated showing that: Chitosan(Ch) led to M2c macrophage polarization in vitro; the degree of acetylation of Ch affected macrophage phenotype in vivo; Fibrinogen(Fg)-modified Ch increased NK adhesion, modulated MSC invasion and lead to increased resorption by osteoclasts. In a rat critical size bone defect model higher bone formation correlated with higher proportion of B and myeloid cells in draining lymph nodes for Ch-Fg materials.

Stem-cell microenvironments in regeneration/repair

Pre-clinical testing of human Warton’s jelly-derived MSC (ECBio) and of adult cardiac progenitors (CPC) revealed a paracrine beneficial effect upon MI. A central role of YAP/TAZ on adult CPC mechano-sensing and fate decision has been further demonstrated.

Microenvironments in cancer invasion and metastasis

Human macrophages (MF) stimulate gastric and colorectal cancer cell invasion, motility/migration and proteolysis. MF-mediated invasion requires the activation of EGF receptor. M1- MF were less efficient in stimulating cancer cell invasion, migration, proteolysis and angiogenesis than M2- MF.

Morphology of macrophages differentiated on surfaces can be observed by staining for F-actin filaments (red) and nuclei (green).