Angew. Chem. Int. Ed.http://doi.org/fz8rxc (2012)

The therapeutic potential of mesenchymal stem cells (MSCs) is known to be enhanced by their formation into enlarged spheroids of cells. In the centre of these spheroids, as a consequence of a reduced supply of oxygen and nutrients, however, hypoxic conditions can be present. These conditions decrease MSC survival and lower the efficacy of MSC-based therapy involving spheroid transplantation. Now, Younan Xia and colleagues show that the anti-apoptotic activity of human MSCs (hMSCs) can be enhanced by the intracellular delivery of polyplexes composed of the biodegradable polymer, branched poly(disulphide amine) (PDA), and Fas-silencing small interfering RNA (Fas siRNA). These Fas-silenced hMSCs are cultured as enlarged spheroids under hypoxic conditions and the gene-silencing efficiency of the polyplexes is about 1.5 times higher than hMSCs treated with polyplexes formed from Fas siRNA and polyethylenimine. Also, the expression of angiogenic and anti-apoptotic growth factors is increased in the spheroids treated with the Fas siRNA–PDA polyplex.