Olfactory Mucosa Autografts in Human Spinal Cord Injury: A Pilot Clinical Study

Abstract

Background/Objective: Olfactory mucosa is a readily accessible source of olfactory ensheathing and stem-like progenitor cells for neural repair. To determine the safety and feasibility of transplanting olfactory mucosa autografts into patients with traumatically injured spinal cords, a human pilot clinical study was conducted.Methods: Seven patients ranging from 18 to 32 years of age (American Spinal Injury Association [ASIA] class A) were treated at 6 months to 6.5 years after injury. Olfactory mucosa autografts were transplanted into lesions ranging from 1 to 6 cm that were present at C4-T6 neurological levels. Operations were performed from July 2001 through March 2003. Magnetic resonance imaging (MRI), electromyography (EMG), and ASIA neurological and otolaryngological evaluations were performed before and after surgery.Results: MRI studies revealed moderate to complete filling of the lesion sites. Two patients reported return of sensation in their bladders, and one of these patients regained voluntary contraction of anal sphincter. Two of the 7 ASIA A patients became ASIA C. Every patient had improvement in ASIA motor scores. The mean increase for the 3 subjects with tetraplegia in the upper extremities was 6.3 6 1.2 (SEM), and the mean increase for the 4 subjects with paraplegia in the lower extremities was 3.9 6 1.0. Among the patients who improved in their ASIA sensory neurological scores (all except one patient), the mean increase was 20.3 6 5.0 for light touch and 19.7 6 4.6 for pinprick. Most of the recovered sensation below the initial level of injury was impaired. Adverse events included sensory decrease in one patient that was most likely caused by difficulty in locating the lesion, and there were a few instances of transient pain that was relieved by medication. EMG revealed motor unit potential when the patient was asked to perform movement.Conclusion: This study shows that olfactory mucosa autograft transplantation into the human injured spinal cord is feasible, relatively safe, and potentially beneficial. The procedure involves risks generally associated with any surgical procedure. Long-term patient monitoring is necessary to rule out any delayed side effects and assess any further improvements.

Neurological outcome in surgically treated patients with incomplete closed traumatic cervical spinal cord injury

“…Both conservative and surgical management modalities should be discussed with patients before obtaining informed consent. In line with newer developments in stem cell research and olfactory ensheathing cell transplant, 18,19 the importance of well preserved cord, without any encroachment of the canal from bony fragments and in good alignment, may be the key in the success of any future treatment options to come. Resorption and remodeling of the canal do, however, occur naturally and without surgery.…”

A Systematic Review of Cellular Transplantation Therapies for Spinal Cord Injury

“…Intriguingly, significant improvements were still observed when these transplantations were performed 4 weeks after injury (Lu et al, 2002); however, these results were not seen in a formally conducted replication study that was performed in the laboratory of Steward and colleagues (2006). It is worth mentioning that a similar protocol is already used in chronically injured humans using an autotransplantation paradigm (Lima et al, 2006). While this systematic review of cell transplantation was in review for publication, an unblinded, non-randomized study by Lima and colleagues (2010) reported improvements in 11 of 20 individuals with chronic (>18 months) SCI, including six individuals who improved from an AIS score of A to C (motor=sensory complete to motor and sensory incomplete).…”

The Immunohistochemical Characterization of Human Fetal Olfactory Bulb and Olfactory Ensheathing Cells in Culture as a Source for Clinical CNS Restoration

“…Moreover, transplanted OECs promote neuroplasticity in murine models of stroke (Shyu et al, 2008), restore functional deficits in rat model of Parkinson's disease (Agrawal et al, 2004), and OECs have been transplanted to an amyotrophic lateral sclerosis (ALS) mouse model (Morita et al, 2008). In clinic, Lima et al (2006) and Feron et al (2005) used adult autologous olfactory mucosa OECs from patients to repair spinal cord injury. Huang and colleagues (Beijing, China) treated hundreds of patients with spinal cord injury by transplantation of the cultured OECs from human fetal olfactory bulbs (Huang et al, 2003).…”