Fig. 3

Systemic injection of hMSCs in established orthotopic xenografts of U87MG cells. a Schematic drawing of systemic injections of m-Cherry hMSCs in athymic rats with established brain xenografts of U87MG cells. The hMSCs were injected either into the femoral vein (A), or into the common carotid artery (B), or into the common carotid artery after ligation of the external carotid artery (C). Intra-arterial injections were performed on the same side of the brain xenograft. b A microvessel lying in the brain hemisphere contralateral to the tumor that was immunostained with antibodies for the endothelium (lectin, CD31), glial cells (GFAP), and blood-brain barrier (BBB) (SMI71). Scale bar = 10 μm. c,d Microphtographs of the brain-tumor interface after intravenous injection of m-Cherry adipose-derived human mesenchymal stem/stromal cells (Ad-hMSCs). Intratumoral Ad-hMSCs were found only in regions with absent perivascular astrocytic endings (c) and SMI71 immunostaining (d). Scale bar = 75 μm. e Microphtographs of tumor microvessels obtained 1 h after intracarotid injection of m-Cherry BM-hMSCs showing transmigration through the vessel wall (center, anti-CD31 in purple; right, lectin in purple). Scale bar = 25 μm. f Detail of a brain xenograft after intracarotid injection of paclitaxel (PTX)-loaded Ad-hMSCs. One Ad-hMSC is surrounded by three multinucleated U87MG tumor cells (yellow arrows). Scale bar = 25 μm