Intrathecal transplantation of olfactory ensheathing cells by lumbar puncture for thoracic spinal cord injury in mice

Abstract

*These authors contributed equally to this workObjectives: To investigate the distribution and function of olfactory ensheathing cells (OECs) following lumbar puncture (LP) transplantation in mouse spinal cord injury (SCI). Methods: OECs were transplanted by LP at level L3-5, 1 week after transected SCI at T8 vertebra. Mice were killed at 3, 21, and 56 days after LP transplantation, and the relative distribution of cells at T8 vertebra was quantitated. The injured spine was also tested by immunohistochemistry to assess neuron regeneration and scar bridging at 8 weeks posttransplantation. Motor functions of mice were evaluated during the observation period using the Basso Mouse Scale. Results: OECs were examined and confirmed by studying cell morphology under phase contrast and immunostaining of NGFR p75. LP-transplanted OECs could be detected just 3 days after transplantation (p75 + area: 0.16 mm 2 ) and accumulated to 0.31 and 0.30 mm 2 at 21 and 56 days postengraftment, respectively. The number of endogenous neurons, −400 to +400 µm, far from the epicenter, in OEC-transplanted mice was more than that in SCI mice without engraftment. SCI lesion of mice in the control group (164.3±3.97 µm) was much longer than that in OECgrafted group (116.7±3.60 µm). Grafts of OECs induced significant functional improvement in mice that underwent T8 vertebral transection, just from 3 days after cell injection. Conclusion: LP is a minimally invasive method for OEC transplantation to treat SCI. This is the first study to visualize the distribution and functions of LP-transplanted OECs in the intact and injured spinal cord.

Intravenous transplantation of olfactory ensheathing cells reduces neuroinflammation after spinal cord injury via interleukin-1 receptor antagonist

“…The safety of cell transplantation also needs to be evaluated by monitoring the viability, biodistribution, and trafficking of the transplanted cells. Previous studies have shown that intraspinal or intrathecal transplantation of OECs has positive results in the treatment of SCI 42 , 43 . However, these methods of transplantation carry some degree of risk for additional neurological damage to the injured spinal cord.…”

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

“…The major challenge associated with cell-based therapy regarding SCI is to find the most cost-effective approaches to noninvasively deliver cells to the therapeutic targets. The current strategies for transplantation of olfactory bulb OECs include intraspinal injection 46 and intrathecal administration 47 . Although these methods are acceptable for scientific studies in animals, they are difficult to implement in clinical practice for treating human SCI.…”

Designing a Clinical Trial with Olfactory Ensheathing Cell Transplantation-Based Therapy for Spinal Cord Injury: A Position Paper

“…In recent years, nearly 20% of the cell transplantation-based clinical trials for SCI were conducted around the use of OECs. OECs have been proven safe for transplantation in animal spinal cord injury models and they have shown varying degrees of success at restoring sensory, motor, and autonomic functions following treatments in rodents [ 18 , 19 , 20 , 32 , 33 , 34 , 35 , 36 , 37 ], canine [ 15 ], and primate models [ 17 ]. Based on the evidence from pre-clinical studies, OECs are a promising, low-risk therapeutic candidate for clinical translation with a high chance of success.…”