Development of Good Manufacturing Practice-Compatible Isolation and Culture Methods for Human Olfactory Mucosa-Derived Mesenchymal Stromal Cells.

Demyelination in the central nervous system (CNS) resulting from injury or disease can cause loss of nerve function and paralysis. Cell therapies intended to promote remyelination of axons are a promising avenue of treatment, with mesenchymal stromal cells (MSCs) a prominent candidate. We have previously demonstrated that MSCs derived from human olfactory mucosa (hOM-MSCs) promote myelination to a greater extent than bone marrow-derived MSCs (hBM-MSCs). However, hOM-MSCs were developed using methods and materials that were not good manufacturing practice (GMP)-compliant. Before considering these cells for clinical use, it is necessary to develop a method for their isolation and expansion that is readily adaptable to a GMP-compliant environment. We demonstrate here that hOM-MSCs can be derived without enzymatic tissue digestion or cell sorting and without culture antibiotics. They grow readily in GMP-compliant media and express typical MSC surface markers. They robustly produce CXCL12 (a key secretory factor in promoting myelination) and are pro-myelinating in in vitro rodent CNS cultures. GMP-compliant hOM-MSCs are comparable in this respect to those grown in non-GMP conditions. However, when assessed in an in vivo model of demyelinating disease (experimental autoimmune encephalitis, EAE), they do not significantly improve disease scores compared with controls, indicating further pre-clinical evaluation is necessary before their advancement to clinical trials.

Human olfactory mesenchymal stromal cell transplantation ameliorates experimental autoimmune encephalomyelitis revealing an inhibitory role for IL16 on myelination.

One of the therapeutic approaches for the treatment of the autoimmune demyelinating disease, multiple sclerosis (MS) is bone marrow mesenchymal stromal cell (hBM-MSCs) transplantation. However, given their capacity to enhance myelination in vitro, we hypothesised that human olfactory mucosa-derived MSCs (hOM-MSCs) may possess additional properties suitable for CNS repair. Herein, we have examined the efficacy of hOM-MSCs versus hBM-MSCs using the experimental autoimmune encephalomyelitis (EAE) model. Both MSC types ameliorated disease, if delivered during the initial onset of symptomatic disease. Yet, only hOM-MSCs improved disease outcome if administered during established disease when animals had severe neurological deficits. Histological analysis of spinal cord lesions revealed hOM-MSC transplantation reduced blood-brain barrier disruption and inflammatory cell recruitment and enhanced axonal survival. At early time points post-hOM-MSC treatment, animals had reduced levels of circulating IL-16, which was reflected in both the ability of immune cells to secrete IL-16 and the level of IL-16 in spinal cord inflammatory lesions. Further in vitro investigation revealed an inhibitory role for IL-16 on oligodendrocyte differentiation and myelination. Moreover, the availability of bioactive IL-16 after demyelination was reduced in the presence of hOM-MSCs. Combined, our data suggests that human hOM-MSCs may have therapeutic benefit in the treatment of MS via an IL-16-mediated pathway, especially if administered during active demyelination and inflammation.

Through-and-Through Mattress Suturing Versus Tie-Over Dressing in Full-Thickness Skin Graft Reconstruction.

OBJECTIVE: To compare the outcomes of securing full-thickness skin grafting (FTSG) with through-and-through mattress suturing versus the classic tie-over and pressure dressing and identify the associated risk factors of graft failure. METHODS: A single-institution, retrospective case series of patients who had undergone excision of head and neck skin lesions requiring FTSG over a 10-year period was reviewed. RESULTS: In total, 128 FTSG reconstructions were performed. The follow-up period ranged from 1 to 192 weeks. The observed graft take rate was 86.4%. There was no significant difference in the outcome when the surgical fixation technique was compared. Age, sex, or defect area did not affect the graft take rate. Smoking and the use of anticoagulants were not found to be contributory factors to graft failure. CONCLUSION: Simple through-and-through mattress suturing provides adequate graft take, while minimizing tissue handling of the graft and reducing surgical time in comparison to the traditional tie-over and pressure technique.

Bilateral haemorrhagic vocal cords with supraglottic bruising following blunt laryngeal trauma.

Isolated vocal cord haemorrhage secondary to blunt neck trauma is rare. It can lead to compromised airway in a patient with otherwise minimal clinical findings. The authors report a patient with traumatic haemorrhage in the supraglottis and vocal cords. A 24 years old Caucasian male presented with acute hoarseness, dysphagia, and a tender anterior neck swelling 3 hours after he was punched in his neck. There was no stridor or surgical emphysema. Flexible pharyngolaryngoscopy revealed no endolaryngeal mucosal tear but evidence of bleeding into his true vocal cords. The patient was successfully treated with dexamethasone, analgesia and voice rest. The patient refused to stay in hospital for overnight airway monitoring. The authors believe that all patients presenting with a blunt neck trauma should undergo laryngoscopy for assessment and monitoring of the airway.

Primary carcinosarcoma of the parotid gland.

Carcinosarcoma is a rare malignant 'mixed' tumour in the head and neck region. We present a case of carcinosarcoma in a long standing parotid lump and share our experience in the management of the disease together with a review of recent English literature on the subject.

Increased nerve fiber expression of sensory sodium channels Nav1.7, Nav1.8, And Nav1.9 in rhinitis.

INTRODUCTION: Voltage-gated sodium channels Nav1.7, Nav1.8, and Nav1.9 are involved in nerve action potentials and have been proposed to underlie neuronal hypersensitivity. We have therefore studied their levels in allergic and nonallergic rhinitis. MATERIALS AND METHODS: Inferior turbinate biopsies from 50 patients (n = 18 controls, n = 20 allergic, and n = 12 nonallergic rhinitis) were studied by immunohistology using antibodies to Nav1.7, Nav1.8, and Nav1.9, the structural nerve marker (protein gene product [PGP]9.5), nerve growth factor (NGF), mast cells (c-kit), macrophages (CD68), and T cells (CD3). Sodium channel-positive nerve fibers were counted per millimeter length of subepithelium, and immunoreactivity for inflammatory cell markers PGP9.5 and NGF were image analyzed. RESULTS: All three sodium channel-immunoreactive nerve fiber numbers were significantly increased in allergic (Nav1.7, P = .0004; Nav1.8, P = .028; Nav1.9, P = .02) and nonallergic (Nav1.7, P = .006; Nav1.8, P = .019; Nav1.9, P = .0037) rhinitis. There was a significant increase of subepithelial innervation (PGP9.5, P = .01) and epithelial NGF immunoreactivity (P = .03) in nonallergic rhinitis, comparable with our previous report in allergic rhinitis. Inflammatory cell markers were significantly increased in allergic (mast cells, P = .06; macrophages, P = .044; T cells, P = .007) but not nonallergic rhinitis. CONCLUSION: The increased levels of sensory sodium channels in allergic and nonallergic rhinitis may contribute to the hypersensitive state, irrespective of the degree of active inflammation. Selective blockers of these sodium channels, administered topically, may have therapeutic potential in rhinitis.

Corrosive injury to upper gastrointestinal tract: Still a major surgical dilemma.

In the developed and developing countries, corrosive injury to the gastrointestinal system as a consequence of either accidental ingestion or as a result of self-harm has become a less common phenomenon compared to decades ago. This could partly be attributed to the tighter legislation imposed by the government in these countries on detergents and other corrosive products and general public awareness. Most busy upper gastrointestinal surgical units in these countries, especially in the developed countries will only encounter a small number of cases per year. Up to date knowledge on the best management approach is lacking. In this article, we present our experience of two contrasting cases of corrosive injury to the upper gastrointestinal tract in our thoracic unit in the last 2 years and an up-to-date Medline literature search has been carried out to highlight the areas of controversies in the management of corrosive injuries of the upper gastrointestinal tract. We concluded that the main principle in managing such patients requires a good understanding of the pathophysiology of corrosive injury in order to plan both acute and future management. Each patient must be evaluated individually as the clinical picture varies widely. Signs and symptoms alone are an unreliable guide to injury.