Non-clinical Study of Biodistribution of Human Immature Dental Pulp Stem Cells (Nestacell® Product) Following Intravenous Administration in Mice

Abstract Background: Although the safety of mesenchymal stroma/stem cells (MSCs)-based therapies had already extensively demonstrated, non-clinical biodistribution studies are essential for predicting the safety and efficacy of these cells. Herein we assessed the biodistribution of human immature dental pulp stem cells (hIDPSCs), which has investigated as a candidate for the treatment of Huntington’s disease (HD). Method: For this, we intravenously transplanted hIDPSCs transfected with luciferase or labeled with magnetic nanoparticle in C57BL/6 mice and performed the bioluminescence image (BLI) or inductively coupled plasma mass spectrometer (ICP-MS) to quantity in vivo and ex vivo biodistribution after 4h, 24h, 3, 7, and 30 days of the hIDPSCs administration. Results: BLI’s results showed the presence of hIDPSCs in the chest, lungs, and head after 4h, 24 h, and 3 days of the cell transplantation. No bioluminescent signal was observed in the chest or head on days 7 and 30 days. The ICP-MS’s results showed that the hIDPSCs engraft into the liver, kidney, heart, and lungs. However, the number of hIDPSCs in these sites significantly reduced from the seventh day, being undetectable on the 30th day. By contrast, we observed that the hIDPSCs not only engrafted into the brain, but also remain in this organ for 30 days. Conclusion: These data provide evidence that the hIDPSCs successfully engraft and remain in the brain for until 30 days after the cell transplantation, demonstrating that these cells can migrate and homing to the brain, being a useful candidate for the treatment of neurodegenerative disorders, such as HD.