NK cell-based regulation of in vitro mesenchymal stem cell differentiation potential in osteogenic or chondrogenic culture conditions

Anno
2018
Proponente Giovanni Bernardini - Professore Associato
Sottosettore ERC del proponente del progetto
Componenti gruppo di ricerca
Abstract

Abnormal formation of new bone tissue has been observed in osteoarthritis (OA), a degenerative disease affecting joint, cartilage and bone. A series of events characterize OA, including degradation of cartilage matrix components associated with increased synthesis and activation of pro-inflammatory mediators and enhanced expression of bone erosion factors and up-regulation of bone remodeling proteins. Although, much is known about the pro-inflammatory and anti-inflammatory cytokines milieu contributing to bone remodeling and repair, the immune cell source of these factors and their reciprocal interaction are poorly understood. This is an important topic of investigation as several immune cell lineages were shown to regulate mesenchymal stem cell (MSC) migration and osteogenic capacity on one side and cartilage degradation on the other. We have documented that NK cells and neutrophils have a disease-promoting role in experimental OA. Since our preliminary observations indicate a role of NK cells in the repair phase of the disease, we hypothesized that NK cell interaction with other immune cells could affect the local growth factor environment, regulating osteogenesis and chondrogenesis.
This proposal is aimed to analyze the ability of NK cells to alter MSC chondrogenic/osteogenic potential in vitro. We will study how NK cells modulate the osteogenic vs chondrogenic differentiation of MSCs in normal conditions or in conditions guiding (i.e. by BMP-2, GDF-5 supplementation) MSC differentiation toward a specific cell lineage. We will investigate the contribution of CXCR3 in the migration of NK cells at the damage/remodeling phase of collagenase-induced OA and in MSC regenerative capacity. The study will provide novel facets on the NK cell-based mechanisms controlling bone/cartilage repair that will be of interest for regenerative medicine.

ERC
LS6_1, LS6_3
Keywords:
IMMUNOLOGIA, IMMUNITA¿ INNATA, IMMUNOPATOLOGIA, DIFFERENZIAMENTO, FISIOLOGIA E DINAMICA CELLULARE

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