A MSC population with enhanced response towards tumor stroma

BOLONTRADE, MARCELA F.; SGANGA, LEONARDO; CIOLFI, FEDERICO; GARCIA, MARIANA; PIAGGIO, EDUARDO; SORRENTINO, MIGUEL ANGEL; ROBINSON, ANIBAL; MAZZOLINI, GUILLERMO; PODHAJCER, OSVALDO

Toronto

Simposio; International Society for Stem Cell Research 9th Annual Meeting; 2011

ISSCR

Mesenchymal stromal Cells (MSCs) compose a heterogeneous cell population with multipotent capacities, which have been demonstrated to have the ability to preferentially migrate and home into sites of tissue remodeling, such as a tumor site. Most of the studies carried out have focused on the ability of the heterogeneous MSC population as a whole to arrive at the site of stress such as the tumor onset niche. Little is known about the biological properties of the different subpopulations that compose the original MSCs population. This may undermine clinical applications in terms of the advantages and disadvantages of different cellular compartments to arrive to a remodeling site and be capable of contributing to the supportive tissue in a disease setting. Using human adult Mesenchymal stromal cells from voluntary donors for allogeneic transplants, our purpose is to find MSCs subpopulations with a differential behaviour in terms of the recruiting / homing response to the tumour. To address this issue we have carried out chemotaxis and adhesion assays to identify MSCs subpopulations that differ in their responsive properties towards a tumour. In vivo assays were carried out to point at differential behaviour towards the tumour stroma. Thus, we were able to identify subpopulations with a dissimilar behavioural response towards chemotactic agents and its ability to elicit an angiogenic response, and with a distinct adhesive response towards ECM proteins and microendothelia. Depending on the disease setting, a distinct population of MSCs may be desirable to enrich for the desired therapeutic effect. Thus, for tumour targeting strategies, the population that exhibit a more pronounced migratory and adhesive behaviour as well as invasive in vivo response towards the tumour could turn into the most useful cell tool for tumour targeting strategies. These results also bring insight into the potential richness of MSCs as cell therapy agents.