Short-, middle- and long-term safety of superparamagnetic iron oxide-labeled allogeneic bone marrow stromal cell transplantation in rat model of lacunar infarction.
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| Abstract |
Recently, both basic and clinical studies demonstrated that bone marrow stromal cell (BMSC) transplantation therapy can promote functional recovery of patients with CNS disorders. A non-invasive method for cell tracking using MRI and superparamagnetic iron oxide (SPIO)-based labeling agents has been applied to elucidate the behavior of transplanted cells. However, the long-term safety of SPIO-labeled BMSCs still remains unclear. The aim of this study was to investigate the short-, middle- and long-term safety of the SPIO-labeled allogeneic BMSC transplantation. For this purpose, BMSCs were isolated from transgenic rats expressing green fluorescent protein (GFP) and were labeled with SPIO. The Na/K ATPase pump inhibitor ouabain or vehicle was stereotactically injected into the right striatum of wild-type rats to induce a lacunar lesion (n = 22). Seven days after the insult, either BMSCs or SPIO solution were stereotactically injected into the left striatum. A 7.0-Tesla MRI was performed to serially monitor the behavior of BMSCs in the host brain. The animals were sacrificed after 7 days (n = 7), 6 weeks (n = 6) or 10 months (n = 9) after the transplantation. MRI demonstrated that BMSCs migrated to the damage area through the corpus callosum. Histological analysis showed that activated microglia were present around the bolus of donor cells 7 days after the allogeneic cell transplantation, although an immunosuppressive drug was administered. The SPIO-labeled BMSCs resided and started to proliferate around the route of the cell transplantation. Within 6 weeks, large numbers of SPIO-labeled BMSCs reached the lacunar infarction area from the transplantation region through the corpus callosum. Some SPIO nanoparticles were phagocytized by microglia. After 10 months, the number of SPIO-positive cells was lower compared with the 7-day and 6-week groups. There was no tumorigenesis or severe injury observed in any of the animals. These findings suggest that BMSCs are safe after cell transplantation for the treatment of stroke.
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| Authors | Chengbo Tan, Hideo Shichinohe, Takeo Abumiya, Naoki Nakayama, Ken Kazumata, Masaaki Hokari, Shuji Hamauchi, Kiyohiro Houkin |
| Journal | Neuropathology : official journal of the Japanese Society of Neuropathology (Neuropathology) Vol. 35 Issue 3 Pg. 197-208 (Jun 2015) ISSN: 1440-1789 [Electronic] Australia |
| PMID | 25376270 (Publication Type: Journal Article) |
| Copyright | © 2014 Japanese Society of Neuropathology. |
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