Utilización de células madre adultas de médula osea para el tratamiento del cáncer hepático

Zusammenfassung

In the adult bone marrow, there are different populations of stem cells that have particular tropism to sites of injury, like tumours, with the capacity of contributing to neovascularization. The hepatocellular carcinoma is a tumor characterized by potent angiogenic activity. The formation of new tumoral vessels involves a continuous recruitment of circulating endothelial progenitor cells derived from the bone marrow. Our aim was to determine the capacity of bone marrow stem cells to colonize hepatocarcinoma tumour nodules once administered intravenously. These cells were intended to convey the expression of desired gene products inside the tumour mass as a means to treat cancer. We were able to isolate and expand MAPCs and MSCs from male Buffalo rats and human bone marrow samples. We transduced the bone marrow-derived MAPCs and MSCs with GFP-coding lentiviral vectors at high efficiency. These cells were efficiently recruited in vivo by tumour nodules in two orthotopic hepatocarcinoma models, as these GFP-positive cells were detected in the tumour periphery 17 days after cell infusion. Rat and human MAPCs differentiated in vitro into endothelial lineage, and in vivo, they contributed to the formation of new tumour blood vessels. Moreover, rat MSCs were able to promote the growth of a syngenic orthotopic hepatocarcinoma developed in Buffalo rats, while, on the contrary, human MSC inhibited the growth of a human orthotopic hepatocarcinoma induced in immunodeficient mice. This therapeutic effect has been confirmed in a co-culture assay, showing that human MSCs were able to inhibit tumor cell proliferation in vitro. In conclusion, we demonstrate that lentiviral vectors can be used to convert bone marrow-derived adult stem cells into vehicles capable of delivering the expression of desired genes within the tumour mass. Our data point to a new system to treat liver cancer by combining gene and cell therapy strategies.