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 +/- 1.2 (SEM), and the mean increase for the 4 subjects with paraplegia in the lower extremities was 3.9 +/- 1.0. Among the patients who improved in their ASIA sensory neurological scores (all except one patient), the mean increase was 20.3 +/- 5.0 for light touch and 19.7 +/- 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.

Figure 1. Surgical field, preoperative MRI, and postoperative MRI from 2 patients. (a) Surgical field from patient five revealing 2 cystic cavities that appear to be connected by scar tissue (at end of forceps). (b) Preoperative MRI at 30 months after injury shows the lesion area that extends from T4 vertebral level (upper arrow) to T6 (lower arrow) and measured about 4 cm in the T2-weighted sagittal MRIs (with artifacts from the fixing bars). (c) Six-month postoperative MRI showing presumed filling of the cavity with “salt and pepper” appearance. (d) Surgical field from patient three revealing 1 cystic cavity. (e) T1-weighted sagittal MRIs show preoperative MRI at 36 months after injury and lesion (arrow) approximately 1 cm in length at C3–C4. (f) Six-month postoperative MRI showing presumed filling of the cavity (arrow).

Figure 2. Graphs of the component scores of the ASIA neurological examination starting preoperatively and at 6-month intervals for each patient.

Figure 3. EMG with motor muscle potentials retrieved by voluntary control on left long adductor muscle in patient one at 10-month evaluation, preceded by no activity recording at rest.

Figure 4. Sections of the scar tissue from the spinal cord removed before grafting the olfactory mucosa in patients 5 and 3. (a) Scar containing large regions of collagen with some interspersed Schwann cell ensheathed nerve fibers. Collagen bundles are stained green and an axonal bundle is marked with an arrow. Masson trichrome, ×200. (b) “Pure” glial scar that is made up of reddish-brown GFAP-positive fibers that are loosely woven close to the cavity (top) and more tightly woven at a distance (bottom). Reactive astrocytes and their fibers (processes) contain large amounts of GFAP that is stained reddish-brown. GFAP immunohistochemistry, ×200.