Intravenous transplantation of olfactory bulb ensheathing cells for a spinalcord hemisection injury rat model

摘要

Cellular transplantation strategies utilizing intraspinal or intrathecal olfactoryensheathing cells (OECs) have been reported as beneficial for spinal cord injury (SCI).However, there are many disadvantages of these methods, including additional trauma to thespinal cord parenchyma and technical challenges. Therefore, we investigated thefeasibility and potential benefits of intravenous transplantation of OECs in a rathemisection SCI model. OECs derived from olfactory bulb tissue were labeled with quantumdots (QDs), and their biodistribution after intravenous transplantation was tracked usinga fluorescence imaging system. Accumulation of the transplanted OECs was observed in theinjured spinal cord within 10 min, peaked at seven days after cell transplantation, anddecreased gradually thereafter. This time window corresponded to the blood–spinal cordbarrier (BSCB) opening time, which was quantitated with the Evans blue leakage assay.Using immunohistochemistry, we examined neuronal growth (GAP-43), remyelination (MBP), andmicroglia (Iba-1) reactions at the lesion site. Motor function recovery was also measuredusing a classic open field test (Basso, Beattie and Bresnahan score). Compared with thegroup injected only with QDs, the rats that received OEC transplantation exhibited aprominent reduction in inflammatory responses, increased neurogenesis and remyelination,and significant improvement in motor function. We suggest that intravenous injection couldalso be an effective method for delivering OECs and improving functional outcomes afterSCI. Moreover, the time course of BSCB disruption provides a clinically relevanttherapeutic window for cell-based intervention.