Umbilical cord-derived mesenchymal stromal cells (UCMSCs) have potential applications in regenerative medicine. UCMSCs have been demonstrated to repair tissue damage in many inflammatory and degenerative diseases. We have previously shown that UCMSC exosomes reduce nerve injury-induced pain in rats. In this study, we characterized UCMSC exosomes using RNA sequencing and proteomic analyses and investigated their protective effects on cisplatin-induced hearing loss in mice. Two independent experiments were designed to investigate the protective effects on cisplatin-induced hearing loss in mice: (i) chronic intraperitoneal cisplatin administration (4 mg/kg) once per day for 5 consecutive days and intraperitoneal UCMSC exosome (1.2 μg/μL) injection at the same time point; and (ii) UCMSC exosome (1.2 μg/μL) injection through a round window niche 3 days after chronic cisplatin administration. Our data suggest that UCMSC exosomes exert protective effects in vivo. The post-traumatic administration of UCMSC exosomes significantly improved hearing loss and rescued the loss of cochlear hair cells in mice receiving chronic cisplatin injection. Neuropathological gene panel analyses further revealed the UCMSC exosomes treatment led to beneficial changes in the expression levels of many genes in the cochlear tissues of cisplatin-injected mice. In conclusion, UCMSC exosomes exerted protective effects in treating ototoxicity-induced hearing loss by promoting tissue remodeling and repair.

https://www.mdpi.com/1422-0067/22/13/6664/pdf

Umbilical Cord Mesenchymal Stromal Cell-Derived Exosomes Rescue the Loss of Outer Hair Cells and Repair Cochlear Damage in Cisplatin-Injected Mice

Head and neck structures govern the vital functions of breathing and swallowing. Additionally, these structures facilitate our sense of self through vocal communication, hearing, facial animation, and physical appearance. Loss of these functions can lead to loss of life or greatly affect quality of life. Regenerative medicine is a rapidly developing field that aims to repair or replace damaged cells, tissues, and organs. Although the field is largely in its nascence, regenerative medicine holds promise for improving on conventional treatments for head and neck disorders or providing therapies where no current standard exists. This review presents milestones in the research of regenerative medicine in head and neck surgery.

https://www.bmj.com/content/bmj/369/bmj.m718.full.pdf

Advances in regenerative medicine for otolaryngology/head and neck surgery

Newborn stem cell banking began with the establishment of cord blood banks more than 25 years ago. Over the course of nearly three decades, there has been considerable evolution in the clinical application of stem cells isolated from newborn tissues. The industry now finds itself at an inflection point as personalized medicine and regenerative medicine continue to advance. In this review, we summarize our perspective on newborn stem cell banking in the context of the future potential that stem cells from perinatal tissues are likely to play in nascent applications. Specifically, we describe the relevance of newborn stem cell banking and how the cells stored can be utilized as starting material for the next generation of advanced cellular therapies and personalized medicine.

https://www.mdpi.com/2077-0383/8/1/117/pdf

The Future State of Newborn Stem Cell Banking

Up to 1.5 billion people worldwide suffer from various forms of hearing loss, with an additional 1.1 billion people at risk from various insults such as increased consumption of recreational noise-emitting devices and ageing. The most common type of hearing impairment is sensorineural hearing loss caused by the degeneration or malfunction of cochlear hair cells or spiral ganglion nerves in the inner ear. There is currently no cure for hearing loss. However, emerging frontier technologies such as gene, drug or cell-based therapies offer hope for an effective cure. In this review, we discuss the current therapeutic progress for the treatment of hearing loss. We describe and evaluate the major therapeutic approaches being applied to hearing loss and summarize the key trials and studies.

Recent Therapeutic Progress and Future Perspectives for the Treatment of Hearing Loss

Background: Although many therapeutic approaches have been attempted to treat spinal cord injury, cellular transplantation offers the greatest promise in reconstituting the architecture of the damaged cord. Methods: A literature review was conducted to search for clinical trials investigating stem cells as treatment for spinal cord injury in the United States. Results: Overall, eight studies met inclusion criteria. Of the included studies, four were identified as being terminated, suspended, or not yet recruiting. Two studies were identified as currently recruiting, including one phase one trial evaluating stereotactic injections of human spinal cord-derived neural stem cells in patients with chronic spinal cord injuries, and one trial of transplantation of autologous bone marrow derived stem cells via paraspinal injections, intravenous injections, and intranasal placement. One study was identified as an active study, a phase one trial of intrathecal injection of 100 million autologous, ex-vivo expanded, adipose-derived mesenchymal stem cells. One trial that was listed as completed is a phase 1/2a, dose escalation study, investigating stereotactic injection of human embryonic stem cell derived oligodendrocyte progenitor cells. Conclusions: Although few significant publications have emerged to this point, current trial results are promising.

https://www.mdpi.com/2305-6320/7/5/27/pdf

Stem Cell Clinical Trials in Spinal Cord Injury: A Brief Review of Studies in the United States.

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.

Progenitor cell therapy for acquired pediatric nervous system injury: Traumatic brain injury and acquired sensorineural hearing loss.

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.

https://www.intechopen.com/citation-pdf-url/68076

Progenitor Cell Therapy for Sensorineural Hearing Loss in Infants

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.

/pdf/safety-of-autologous-umbilical-cord-blood-therapy-for-1st3hzeuu9.pdf

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

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Progenitor cell therapy for acquired pediatric nervous system injury: Traumatic brain injury and acquired sensorineural hearing loss.

Progenitor Cell Therapy for Sensorineural Hearing Loss in Infants

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