Fascin in Mesenchymal Stem Cell Function

Mesenchymal stem cells (MSCs) are adult stem cells that can be found in different tissues and are characterized by self-renewing capacity with the ability to differentiate into various cell lineage including osteocytes, adipocytes and chondrocytes. Moreover, MSCs were found to immune-modulate many immune cells either through suppressing their proliferation or skewing their differentiation. The actin-bundling protein (fascin) was found to be selectively expressed in mature dendritic cells and neuronal cells. In dendritic cells, fascin contributes to cell morphology, migration, adhesion and ability to bind and activate immune response. Our preliminary results, showed fascin expression in mouse bone marrow-derived MSCs, but its effect on their morphology and functions remains poorly defined.

In the present study, we aim to use a fascin knockout mouse model to investigate whether fascin have an effect on MSC morphology and whether its expression affects their differentiation potential and immunomodulatory function. MSCs will be isolated and expanded from bone marrow of wild type (fascin+/+), heterozygous (Fascin+/-) and homozygous (Fascin-/-). MSCs will be seeded in special media for each linage and their differentiation potential will be tested using special dyes and RT-PCR screening for selected genes. The effect of fascin loss in MSC on T and B cell proliferation and polarization as well as on the macrophages and dendritic cell differentiation and antigen presentation capability will be assessed. The outcome of this study will expand our understanding of MSC biology and may offer a potential intervention window to enhance the therapeutic use of MSCs.