Safety of Autologous Umbilical Cord Blood Therapy for Acquired Sensorineural Hearing Loss in Children

Abstract

Background and objectives: Sensorineural hearing loss (SNHL) in children is associated with neurocognitive morbidity. The cause of SNHL is a loss of hair cells in the organ of Corti. There are currently no reparative treatments for SNHL. Numerous studies suggest that cord blood mononuclear cells (human umbilical cord blood, hUCB) allow at least partial restoration of SNHL by enabling repair of a damaged organ of Corti. Our objective is to determine if hUCB is a safe treatment for moderate to severe acquired SNHL in children. Subjects and.

Methods: Eleven children aged 6 months to 6 years with moderate to severe acquired SNHL were treated with intravenous autologous hUCB. The cell dose ranged from 8 to 30 million cells/kg body weight. Safety was assessed by measuring systemic hemodynamics during hUCB infusion. Infusion-related toxicity was evaluated by measuring neurologic, hepatic, renal and pulmonary function before and after infusion. Auditory function, auditory verbal language assessments and MRI with diffusion tensor imaging (DTI) were obtained before and after treatment.

Results: All patients survived, and there were no adverse events. No infusionrelated changes in hemodynamics occurred. No infusion-related toxicity was recorded. Five subjects experienced a reduction in auditory brainstem response (ABR) thresholds. Four of those 5 subjects also experienced an improvement in cochlear nerve latencies. Comparison of MRI with DTI sequences obtained before and after treatment revealed increased fractional anisotropy in the primary auditory cortex in three of five subjects with reduced ABR thresholds. Statistically significant (p<0.05) reductions in ABR thresholds were identified.

Conclusions: TIntravenous hUCB is feasible and safe in children with SNHL.

Keywords: Auditory brainstem response; Diffusion tensor imaging; Human umbilical cord blood; Mesenchymal stem cells; Mononuclear fraction; Otoacoustic emission; Sensorineural hearing loss.

Fig. 1.

Graphic representation of the patient enrollment and treatment timeline. CBR: Cord Blood Registry, FHFC: Florida Hospital for Children, FHCPL: Florida Hospital Cell Processing Lab, HLA: human leukocyte antigen, PCP: primary care physician.

Fig. 2.

Representative audiograms (top) and ABR recordings at 4,000 Hz (below) of subject 5 before (left) and after (right) hUCB treatment. The improvements on the behavioral testing (audiogram) match the changes found on the ABR recordings (physiologic). hUCB: human umbilical cord blood, ABR: auditory brainstem response.

Fig. 3.

A: Graphic representation of mean FA in the region of interest of Heschl’s gyrus white matter comparing responding and non-responding study subjects before (pre) and after (post) hUCB treatment. B: Graphic representation of maximal FA at selected sites along the auditory pathways comparing responding (R) and non-responding (NR) study subjects following hUCB treatment. FA: fractional anisotropy, hUCB: human umbilical cord blood, SEM: standard error of the mean.