It has been shown that intra-arterial transplantation of mesenchymal stem cells can enhance stroke recovery in animal models and in humans according to the outcomes of first clinical trials. In vivo tracking of transplanted cells is essential for understanding the mechanisms of their beneficial effects. In these study we evaluated in vivo distribution and migration of human mesenchymal stem cells (hMSCs) and compared it with directly reprogrammed from human bone marrow MSCs neural progenitor cells (drNPCs) in ischemic stroke model in rat
Male Wistar rats 24h after 90 minutes MCAO were transplanted intra-arterial into the right ICA with saline (n=10) and 5x105 in 1 ml MSCs isolated from human placenta (n=15) or NPCs directly reprogrammed from human bone marrow MSCs (n=15) without genetic engineering techniques. For in vivo and ex vivo detection cells were double-labeled with the combination of SPIO and PKH26. 7T-MRI, behavioral test and postmortem immunohistochemistry were performed in dynamic.
After intra-arterial injection all types of transplanted cells were distributed in the hemisphere of administration mainly periphery to the infarction zone and also in brain stem. Cells were visualized inside the vessels in tight contact with the vascular wall. hMSCs remained in the brain for up to 3-4 days, while drNPCs not more than for 24 hours. Transplantation of both types of stem cells induced significantly faster stroke recovery than in animals from control group already after 7d. However, administration only of drNPCs accelerated reduction of stroke volume.
Our results indicate different migration and potential mechanisms of therapeutic action of different stem cells types.