Background and ObjectivesSensorineural 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 MethodsEleven 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.ResultsAll 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.ConclusionsTIntravenous hUCB is feasible and safe in children with SNHL.

Typical language development requires typical hearing. With sensorineural hearing loss (SNHL), the damaged hair cells of the organ of Corti within the cochlea interfere with typical hearing and, as a result, cause impaired language development. Untreated SNHL causes significant neurocognitive differences in affected children. SNHL is a permanent sensory disorder affecting more than 270 million people worldwide. Congenital SNHL is found in 4 of 1000 newborns. Approximately half of congenital SNHL is hereditary and is the result of genetic mutations causing improper development of cochlear hair cells. Non-genetic congenital SNHL is thought to be the result of an injury to the cochlea typically from premature birth, infection, or exposure to ototoxic medications or noise. In mammals, the cochlea is postmitotic at birth, and no spontaneous repair occurs thereafter. Existing treatments for SNHL (hearing aids and cochlear implants) function by augmenting the damaged organ of Corti. No reparative treatments currently exist. In preclinical and clinical studies, progenitor cell therapy (cord blood and mesenchymal stem cells) has shown promise in reversing the underlying pathology of SNHL, the loss of cochlear sensory hair cells. Progenitor cell therapy may also allow functional reorganization of the auditory pathways including primary auditory cortex (Heschl's gyrus). We will present a summary of the effect of hearing loss on auditory development, existing preclinical and clinical data on progenitor cell therapy, and its potential role in the (re)habilitation of non-genetic SNHL.

Failures in electronic packages under thermal fatigue usually result from cracking in solder joints due to creep/fatigue crack growth. Understanding the stress/strain behavior of such solder joints is the first step in characterizing their fracture behavior. A specimen has been developed to determine the stress/strain hysteresis response of 90Pb/10Sn solder joints under cyclic thermal loadings. Simple and special techniques have been developed to fabricate solder joints with relatively high melting points, such as 90Pb/10Sn. Four high-temperature strain gages are mounted on the specimen to measure mechanical strains which provide the basis for determining the shear stress and strain in the solder. A special Wheatstone bridge has been designed to improve the specimen sensitivity, e.g., 20 με/MPa in the test. Shear stresses in the solder as low as 0.5 MPa can be resolved accurately. The specimen was subjected to thermal cycling between 40°C to 140°C, with 10°C/min ramp rate and 10 minute hold times, in a thermal chamber developed in-house. Excellent experimental results have been obtained for 90Pb/10Sn solder joints in that detailed characteristics of stress relaxation and strain creep as a function of temperature were captured. The specimen developed is not only suitable for use in studying the constitutive response of soft solder alloys and other joining materials, such as adhesives, but can serve as a thermal fatigue specimen to study the fracture behavior.

While cell therapies hold remarkable promise for replacing injured cells and repairing damaged tissues, cell replacement is not the only means by which these therapies can achieve therapeutic effect. For example, recent publications show that treatment with varieties of adult, multipotent stem cells can improve outcomes in patients with neurological conditions such as traumatic brain injury and hearing loss without directly replacing damaged or lost cells. As the immune system plays a central role in injury response and tissue repair, we here suggest that multipotent stem cell therapies achieve therapeutic effect by altering the immune response to injury, thereby limiting damage due to inflammation and possibly promoting repair. These findings argue for a broader understanding of the mechanisms by which cell therapies can benefit patients. K E Y W O R D S autologous stem cell transplantation, bone marrow, clinical translation, progenitor cells, umbilical cord blood 1 | INTRODUCTION This review will first consider two neurological conditions with unappreciated similarities: traumatic brain injury (TBI) and sensorineural hearing loss (SNHL), paying particular attention to the role of the immune system in each. Next, it will review laboratory and clinical findings showing improved outcomes for TBI and SNHL upon treatment with allogenic or autologous stem cells, including mesenchymal progenitor cells (MPCs)-a range of nonhematopoietic, mesodermal lineage, multipotent stem cells. 1 Finally, it will evaluate the possible mechanisms of action, concentrating on the immune modulatory properties of MPCs.

Sensorineural Hearing Loss (SNHL) continues to be a significant public health problem with over 270 million affected people worldwide and an incidence that increases with age [1,2]. Some cases of SNHL have a genetic cause, but the majority of SHNL is the result of ototoxic insult [3]