Empty nose syndrome pathogenesis and cell-based biotechnology products as a new option for treatment.

Empty nose syndrome (ENS) is a rare complication that develops after partial or complete turbinectomy. The main feature of ENS is paradoxical nasal obstruction feeling despite objectively wide nasal airway. ENS pathogenesis is multifactorial and includes changes in laminar physiological airflow, disruption of mucosa functions and deficient neural sensation. This leads to the development of ENS symptomatology such as dyspnea, nasal dryness, nasal burning, nasal obstruction, feeling of suffocation and even comorbid psychiatric disorders that significantly impairs life quality. Specific effective treatment of ENS does not exist up to date. In this review we outline existing biomaterial for surgical reconstitution of nasal anatomy and discuss the perspective of stem cell-based technologies in ENS management. The main focus is directed to justification of rationality application of adult mesenchymal stem cells (MSCs) from different tissues origin and neural crest-derived stem cells (NCSCs) based on their intrinsic biological properties. MSCs transplantation may stimulate mucosa tissue regeneration via trophic factors secretion, direct transdifferentiation into epithelial cells and pronounced immunosuppressive effect. From the other hand, NCSCs based on their high neuroprotective properties may reconstitute nerve structure and functioning leading to normal sensation in ENS patients. We postulate that application of cell-based and tissue-engineered products can help to significantly improve ENS symptomatology only as complex approach aimed at reconstitution of nasal anatomy, recovery the nasal mucosa functionality and neural tissue sensation.

Effect of the deuterium on efficiency and type of adipogenic differentiation of human adipose-derived stem cells in vitro.

In this study, we performed an adipogenic differentiation of human adipose-derived stem cells (ADSCs) in vitro with different deuterium content (natural, low and high) in the culture medium during differentiation process with parallel analysis of the gene expression, metabolic activity and cell viability/toxicity. After ADSCs differentiation into adipocytes we have done the analysis of differentiation process efficiency and determined a type of resulting adipocytes (by morphology, gene expression, UCP1 protein detection and adipokine production analysis). We have found that high (5 × 105 ppm) deuterium content significantly inhibit in vitro adipogenic differentiation of human ADSCs compared to the groups with natural (150 ppm) and low (30 ppm) deuterium content. Importantly, protocol of differentiation used in our study leads to white adipocytes development in groups with natural (control) and high deuterium content, whereas deuterium-depleted differentiation medium leads to brown-like (beige) adipocytes formation. We have also remarked the direct impact of deuterium on the cellular survival and metabolic activity. Interesting, in deuterium depleted-medium, the cells had normal survival rate and high metabolic activity, whereas the inhibitory effect of deuterated medium on ADSCs differentiation at least was partly associated with deuterium cytotoxicity and inhibitory effect on metabolic activity. The inhibitory effect of deuterium on metabolic activity and the subsequent decrease in the effectiveness of adipogenic differentiation is probably associated with mitochondrial dysfunction. Thus, deuterium could be considered as an element that affects the substance chirality. These findings may be the basis for the development of new approaches in the treatment of obesity, metabolic syndrome and diabetes through the regulation of adipose-derived stem cell differentiation and adipocyte functions.

Comparative Analysis of Biological Properties of Large-Scale Expanded Adult Neural Crest-Derived Stem Cells Isolated from Human Hair Follicle and Skin Dermis.

INTRODUCTION: The adult neural crest-derived stem cells (NCSCs) have significant perspectives for use in regenerative medicine. The most attractive sources for adult NCSC isolation are the hair follicles (HF) and skin dermis (SD) because of easy access and minimally invasive biopsy. The aim of this study was to compare the biological properties of HF- and SD-derived NCSCs after their large-scale expansion. METHODS: The conventional explant method was used to obtain HF NCSCs. For the isolation of SD NCSCs, a new combined technique consisting of preplating and subsequent culturing in 3D blood plasma-derived fibrin hydrogel was applied. The studied cells were characterized by flow cytometry, ICC, qPCR, Bio-Plex multiplex assay, and directed multilineage differentiation assays. RESULTS: We have obtained both adult SD and HF NCSCs from each skin sample (n = 5). Adult SD and HF NCSCs were positive for key neural crest markers: SOX10, P75 (CD271), NESTIN, SOX2, and CD349. SD NCSCs showed a higher growth rate during the large-scale expansion compared to HF NCSCs (p < 0.01). Final population of SD NCSCs also contained more clonogenic cells (p < 0.01) and SOX10+, CD271+, CD105+, CD140a+, CD146+, CD349+ cells (p < 0.01). Both HF and SD NCSCs had similar gene expression profiling and produced growth factors, but some quantitative differences were detected. Adult HF and SD NCSCs were able to undergo directed differentiation into neurons, Schwann cells, adipocytes, and osteoblasts. CONCLUSION: The HF and SD are suitable sources for large-scale manufacturing of adult NCSCs with similar biological properties. We demonstrated that the NCSC population from SD was homogenous and displayed significantly higher growth rate than HF NCSCs. Moreover, SD NCSC isolation is cheaper, easier, and minimally time-consuming method.