Androgens stimulate many hair follicles to alter hair colour and size via the hair growth cycle; in androgenetic alopecia tiny, pale hairs gradually replace large, pigmented ones. Since stem cell factor (SCF) is important in embryonic melanocyte migration and maintaining adult rodent pigmentation, we investigated SCF/c-Kit signalling in human hair follicles to determine whether this was altered in androgenetic alopecia. Quantitative immunohistochemistry detected three melanocyte-lineage markers and c-Kit in four focus areas: the epidermis, infundibulum, hair bulb (where pigment is formed) and mid-follicle outer root sheath (ORS). Colocalisation confirmed melanocyte c-Kit expression; cultured follicular melanocytes also exhibited c-Kit. Few ORS cells expressed differentiated melanocyte markers or c-Kit, but NKI/beteb antibody, which also recognises early melanocyte-lineage antigens, identified fourfold more cells, confirmed by colocalisation. Occasional similar bulbar cells were seen. Melanocyte distribution, concentration and c-Kit expression were unaltered in balding follicles. Androgenetic alopecia cultured dermal papilla cells secreted less SCF, measured by ELISA, than normal cells. This identifies three types of melanocytelineage cells in human follicles. The c-Kit expression by dendritic, pigmenting, bulbar melanocytes and rounded, differentiated, non-pigmenting ORS melanocytes implicate SCF in maintaining pigmentation and migration into regenerating hair bulbs. Less differentiated, c-Kit-independent cells in the mid-follicle ORS stem cell niche and occasionally in the bulb, presumably a local reserve for long scalp hair growth, implicate other factors in activating stem cells. Androgens appear to reduce alopecia hair colour by inhibiting dermal papilla SCF production, impeding bulbar melanocyte pigmentation. These results may facilitate new treatments for hair colour changes in hirsutism, alopecia or greying.
The clinical use of decellularized cardiac valve allografts is increasing. Long‐term data will be required to determine whether they outperform conventional cryopreserved allografts. Valves decellularized using different processes may show varied long‐term outcomes. It is therefore important to understand the effects of specific decellularization technologies on the characteristics of donor heart valves. Human cryopreserved aortic and pulmonary valved conduits were decellularized using hypotonic buffer, 0.1% (w/v) sodium dodecyl sulfate and nuclease digestion. The decellularized tissues were compared to cellular cryopreserved valve tissues using histology, immunohistochemistry, quantitation of total deoxyribose nucleic acid, collagen and glycosaminoglycan content, in vitro cytotoxicity assays, uniaxial tensile testing and subcutaneous implantation in mice. The decellularized tissues showed no histological evidence of cells or cell remnants and >97% deoxyribose nucleic acid removal in all regions (arterial wall, muscle, leaflet and junction). The decellularized tissues retained collagen IV and von Willebrand factor staining with some loss of fibronectin, laminin and chondroitin sulfate staining. There was an absence of major histocompatibility complex Class I staining in decellularized pulmonary valve tissues, with only residual staining in isolated areas of decellularized aortic valve tissues. The collagen content of the tissues was not decreased following decellularization however the glycosaminoglycan content was reduced. Only moderate changes in the maximum load to failure of the tissues were recorded postdecellularization. The decellularized tissues were noncytotoxic in vitro, and were biocompatible in vivo in a mouse subcutaneous implant model. The decellularization process will now be translated into a good manufacturing practices‐compatible process for donor cryopreserved valves with a view to future clinical use. Copyright © 2016 The Authors Tissue Engineering and Regenerative Medicine published by John Wiley & Sons, Ltd.
A B S T R A C TBackground and purpose of the study: The use of decellularised biological heart valves in the replacement of damaged heart valves offers a promising solution to reduce the degradation issues associated with existing cryopreserved allografts. The purpose of this study was to assess the effect of low concentration sodium dodecyl sulphate decellularisation on the in vitro biomechanical and hydrodynamic properties of cryopreserved human aortic and pulmonary roots. Method: The biomechanical and hydrodynamic properties of cryopreserved decellularised human aortic and pulmonary roots were fully characterised and compared to cellular human aortic and pulmonary roots in an unpaired study. Following review of these results, a further study was performed to investigate the influence of a specific processing step during the decellularisation protocol ('scraping') in a paired comparison, and to improve the method of the closed valve competency test by incorporating a more physiological boundary condition. Results: The majority of the biomechanical and hydrodynamic characteristics of the decellularised aortic and pulmonary roots were similar compared to their cellular counterparts. However, several differences were noted, particularly in the functional biomechanical parameters of the pulmonary roots. However, in the subsequent paired comparison of pulmonary roots with and without decellularisation, and when a more appropriate physiological test model was used, the functional biomechanical parameters for the decellularised pulmonary roots were similar to the cellular roots. Conclusion: Overall, the results demonstrated that the decellularised roots would be a potential choice for clinical application in heart valve replacement.
Piebaldism is characterised by the absence of pigment in patches on the skin, usually present at birth. Mutations in the kit gene are documented. Clinically this disorder can mimic vitiligo. Here, we show for the first time the presence of oxidised pteridine-induced fluorescence in association with H2O2-mediated stress in piebald patches employing Wood's light and in vivo FT-Raman spectroscopy. In situ immunofluorescence data revealed low catalase and methionine sulphoxide reductase A (MSRA) levels whereas thioredoxin reductase and methionine sulphoxide reductase B (MSRB) are not affected. We also show low superoxide dismutase levels in these patients. The presence of thioredoxin reductase provides capacity to reduce H2O2, a mechanism which is absent in vitiligo. Importantly, this enzyme reduces biopterin back to the functioning cofactor 6-tetrahydrobiopterin. The absence of MSRA indicates deficient methionine sulphoxide repair in the cytosol, meanwhile the presence of MSRB is helpful to protect the nucleus. Taken together, we have identified H2O2-mediated stress in piebald skin with distinct differences to vitiligo.
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