Among various strategies employed for spinal cord injury, stem cell therapy is a potential treatment. So far, a variety of stem cells have been evaluated in animal models and humans with spinal cord injury, and epidermal neural crest stem cells represent one of the attractive types in this area. Although these multipotent stem cells have been assessed in several spinal cord injury models by independent laboratories, extensive work remains to be done to ascertain whether these cells can safely improve the outcome following human spinal cord injury. Among the models that closely mimic human spinal cord injury, the in vitro model of injury in organotypic spinal cord slice culture has been identified as one of the faithful platforms for injury-related investigations. In this study, green fluorescent protein-expressing stem cells were grafted into injured organotypic spinal cord slice culture and their survival was examined by confocal microscope seven days after transplantation. Data obtained from this preliminary study showed that these stem cells can survive on top of the surface of injured slices, as observed on day seven following their transplantation. This result revealed that this in vitro model of injury can be considered as a suitable context for further evaluation of epidermal neural crest stem cells before their application in large animals.
- MeSH
- biologické modely MeSH
- buněčná smrt MeSH
- crista neuralis cytologie MeSH
- epidermis cytologie MeSH
- kmenové buňky cytologie MeSH
- kultivované buňky MeSH
- mícha cytologie MeSH
- potkani Wistar MeSH
- transplantace kmenových buněk MeSH
- tvar buňky MeSH
- viabilita buněk MeSH
- zelené fluorescenční proteiny metabolismus MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Epidermal stem cells (ESCs) are crucial for maintenance and self- renewal of skin epithelium and also for regular hair cycling. Their role in wound healing is also indispensable. ESCs reside in a defined outer root sheath portion of hair follicle-also known as the bulge region. ECS are also found between basal cells of the interfollicular epidermis or mucous membranes. The non-epithelial elements such as mesenchymal stem cell-like elements of dermis or surrounding adipose tissue can also contribute to this niche formation. Cancer stem cells (CSCs) participate in formation of common epithelial malignant diseases such as basal cell or squamous cell carcinoma. In this review article, we focus on the role of cancer microenvironment with emphasis on the effect of cancer-associated fibroblasts (CAFs). This model reflects various biological aspects of interaction between cancer cell and CAFs with multiple parallels to interaction of normal epidermal stem cells and their niche. The complexity of intercellular interactions within tumor stroma is depicted on example of malignant melanoma, where keratinocytes also contribute the microenvironmental landscape during early phase of tumor progression. Interactions seen in normal bulge region can therefore be an important source of information for proper understanding to melanoma. The therapeutic consequences of targeting of microenvironment in anticancer therapy and for improved wound healing are included to article.
- MeSH
- epidermis cytologie MeSH
- epitelové buňky patologie MeSH
- fibroblasty patologie MeSH
- hojení ran fyziologie MeSH
- keratinocyty patologie MeSH
- lidé MeSH
- melanom patologie MeSH
- mezenchymální kmenové buňky patologie MeSH
- nádorové kmenové buňky patologie MeSH
- nádorové mikroprostředí fyziologie MeSH
- nádory kůže patologie MeSH
- nika kmenových buněk fyziologie MeSH
- vlasový folikul cytologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
BACKGROUND: Nodular melanoma is one of the most life threatening tumors with still poor therapeutic outcome. Similarly to other tumors, permissive microenvironment is essential for melanoma progression. Features of this microenvironment are arising from molecular crosstalk between the melanoma cells (MC) and the surrounding cell populations in the context of skin tissue. Here, we study the effect of melanoma cells on human primary keratinocytes (HPK). Presence of MC is as an important modulator of the tumor microenvironment and we compare it to the effect of nonmalignant lowly differentiated cells also originating from neural crest (NCSC). METHODS: Comparative morphometrical and immunohistochemical analysis of epidermis surrounding nodular melanoma (n = 100) was performed. Data were compared to results of transcriptome profiling of in vitro models, in which HPK were co-cultured with MC, normal human melanocytes, and NCSC, respectively. Differentially expressed candidate genes were verified by RT-qPCR. Biological activity of candidate proteins was assessed on cultured HPK. RESULTS: Epidermis surrounding nodular melanoma exhibits hyperplastic features in 90% of cases. This hyperplastic region exhibits aberrant suprabasal expression of keratin 14 accompanied by loss of keratin 10. We observe that MC and NCSC are able to increase expression of keratins 8, 14, 19, and vimentin in the co-cultured HPK. This in vitro finding partially correlates with pseudoepitheliomatous hyperplasia observed in melanoma biopsies. We provide evidence of FGF-2, CXCL-1, IL-8, and VEGF-A participation in the activity of melanoma cells on keratinocytes. CONCLUSION: We conclude that the MC are able to influence locally the differentiation pattern of keratinocytes in vivo as well as in vitro. This interaction further highlights the role of intercellular interactions in melanoma. The reciprocal role of activated keratinocytes on biology of melanoma cells shall be verified in the future.
- MeSH
- buněčná diferenciace * genetika MeSH
- chemokin CXCL1 farmakologie MeSH
- dospělí MeSH
- epidermis cytologie patologie MeSH
- fibroblastový růstový faktor 2 farmakologie MeSH
- interleukin-8 farmakologie MeSH
- keratin-10 metabolismus MeSH
- keratin-14 metabolismus MeSH
- keratinocyty cytologie účinky léků metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- melanocyty metabolismus MeSH
- melanom metabolismus patologie MeSH
- metastázy nádorů MeSH
- mezibuněčná komunikace * MeSH
- nádorové buněčné linie MeSH
- proteiny S100 metabolismus MeSH
- senioři MeSH
- stanovení celkové genové exprese MeSH
- vaskulární endoteliální růstový faktor A farmakologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Egg-oil (Charismon©) is known for its beneficial action in wound healing and other skin irritancies and its antibacterial activity. The physiological basis for these actions has been investigated using cells in culture: HaCaT-cells (immortalized human keratinocytes), human endothelial cells in culture (HUVEC), peripheral blood mononuclear lymphocytes (PBML) and a full thickness human skin model (FTSM). Emphasis was on the influence of egg-oil on cell migration and IL-8 production in HaCaT cells, respiration, mitochondrial membrane potential, reactive oxygen (ROS)production and proliferation in HUVEC and HaCaT cells, cytokine and interleukin production in PBML and UV-light induced damage of FTSM. IL-8 production by HaCaT cells is stimulated by egg-oil whilst in phythemagglutinin-activated PBMLs production of the interleukins IL-2, IL-6, IL-10 and IFN-γ and TFN-α is reduced. ROS-production after H2O2 stimulation first is enhanced but later on reduced. Respiration becomes activated due to partial uncoupling of the mitochondrial respiratory chain and proliferation of HaCaT and HUVEC is reduced. Recovery of human epidermis cells in FTSM after UV-irradiation is strongly supported by egg-oil. These results support the view that egg-oil acts through reduction of inflammatory processes and ROS production. Both these processes are equally important in cellular aging as in healing of chronic wounds.
- MeSH
- apoptóza účinky léků MeSH
- buněčné dýchání účinky léků MeSH
- buněčné linie MeSH
- cytokiny metabolismus MeSH
- epidermis cytologie MeSH
- hojení ran účinky léků MeSH
- kultivované buňky MeSH
- kur domácí MeSH
- lidé MeSH
- membránový potenciál mitochondrií účinky léků MeSH
- oleje chemie farmakologie MeSH
- pohyb buněk účinky léků MeSH
- proliferace buněk účinky léků MeSH
- reaktivní formy kyslíku metabolismus MeSH
- sluneční spáleniny farmakoterapie MeSH
- vejce * MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Protein p63 je transkripční faktor, který má významnou funkci ve vývoji a diferenciaci epidermálních struktur a v průběhu tumorigeneze. Je členem rodiny nádorového supresoru p53 a vyskytuje se minimálně v počtu šesti izoforem, které mají během vývoje epidermis a při vzniku a progresi nádorů opačné funkce. Protein p63 ovlivňuje proliferaci a diferenciaci epidermálních buněk v průběhu ontogeneze: vrozené mutace v genu TP63 vedou k různým vývojovým deformacím a odstranění tohoto genu u myší má za následek ztrátu epidermis. Protein p63 také ovlivňuje buněčnou adhezi prostřednictvím regulace desmozomů. Ztráta kontroly proliferace buněk a mezibuněčné adheze je přitom důležitou událostí při vývoji nádorů a vysoká hladina p63 podporuje růst nádorů a brání apoptóze nádorových buněk. Tento přehledový článek stručně shrnuje úlohy proteinu p63 ve vývoji epitelů, buněčné proliferaci, adhezi a migraci a poodhaluje jeho význam při vzniku nádorových onemocnění a tvorbě metastáz.
p63 is a transcription factor which plays an important role in epidermal development, differentiation and tumourigenesis. p63 belongs to the p53 protein family and at least six isoforms were identified to date. p63 isoforms play contrary roles during the development and formation of the epidermis as well as in cancer. p63 participates in epithelial development, where it affects proliferation and differentiation of epidermal cells. Inherited mutations in the TP63 gene generate different developmental defects and p63 knockout in mice results in the absence of epidermis. Another important role of p63 is the control of cell-cell adhesion, where it regulates desmosomes. The loss of proliferation and cell-cell adhesion control are important for tumourigenesis and overexpression of p63 can enhance tumour growth and inhibit apoptosis. This review briefly summarises the roles of p63 in epithelial development, cellular proliferation, adhesion and migration and reveals its share in tumourigenesis and metastasis.
- Klíčová slova
- epidermální vývoj, vývoj nádorového onemocnění, buněčná proliferace,
- MeSH
- buněčná adheze MeSH
- buněčná diferenciace MeSH
- epidermis * cytologie patofyziologie MeSH
- keratinocyty cytologie fyziologie MeSH
- lidé MeSH
- nádorová transformace buněk MeSH
- nádorové supresorové proteiny * fyziologie MeSH
- nádory patofyziologie MeSH
- proliferace buněk MeSH
- proteiny regulující apoptózu MeSH
- transkripční faktory * fyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
A reduction of epidermal club cells and an increase of goblet cells were found in Carassius gibelio during spawning when compared to postspawning. A significantly lower proportion of club cells at spawning was found in diploid males and triploid females than in diploid females. It could be linked to male efforts to avoid a fright reaction and the potential adoption of this strategy by gynogenetic females, or alternatively to a higher parasite infection or immunosuppression during spawning.
- MeSH
- epidermis cytologie MeSH
- kapři anatomie a histologie genetika fyziologie MeSH
- ploidie MeSH
- pohlavní dimorfismus MeSH
- rozmnožování fyziologie MeSH
- sexuální chování zvířat MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The Drosophila retinal determination gene network occurs in animals generally as a Pax-Six-Eyes absent-Dachshund network (PSEDN). For amphioxus, we describe the complete network of nine PSEDN genes, four of which-AmphiSix1/2, AmphiSix4/5, AmphSix3/6, and AmphiEya-are characterized here for the first time. For amphioxus, in vitro interactions among the genes and proteins of the network resemble those of other animals, except for the absence of Dach-Eya binding. Amphioxus PSEDN genes are expressed in highly stage- and tissue-specific patterns (sometimes conspicuously correlated with the local intensity of cell proliferation) in the gastrular organizer, notochord, somites, anterior central nervous system, peripheral nervous system, pharyngeal endoderm, and the likely homolog of the vertebrate adenohypophysis. In this last tissue, the anterior region expresses all three amphioxus Six genes and is a zone of active cell proliferation, while the posterior region expresses only AmphiPax6 and is non-proliferative. In summary, the topologies of animal PSEDNs, although considerably more variable than originally proposed, are conserved enough to be recognizable among species and among developing tissues; this conservation may reflect indispensable involvement of PSEDNs during the critically important early phases of embryology (e.g. in the control of mitosis, apoptosis, and cell/tissue motility).
- MeSH
- adenohypofýza metabolismus růst a vývoj MeSH
- aktivní transport - buněčné jádro MeSH
- centrální nervový systém metabolismus růst a vývoj MeSH
- Chordata genetika růst a vývoj MeSH
- epidermis cytologie růst a vývoj MeSH
- exprese genu MeSH
- financování organizované MeSH
- fylogeneze MeSH
- homeodoménové proteiny analýza genetika metabolismus MeSH
- ledviny metabolismus růst a vývoj MeSH
- messenger RNA analýza metabolismus MeSH
- neurony aferentní metabolismus MeSH
- proteiny nervové tkáně analýza genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
This article summarizes research using cells derived from epidermis of the miniature pigs for use as a cell therapy for skin repair and as a model for squamous carcinoma of the head and neck. Stem cells are an important "tool" for biomedical research. Adult stem cells are defined functionally, as cells that have the capacity to self-renew as well as the ability to generate differentiated cells. They are present in defined tissue microenvironments called niches. Asymmetric mitosis allows them to produce one daughter cell with the properties of stem cells (self-renewal) and a second cell with characteristics of progenitor cells, or transit amplifying cells, which proliferate quickly but with a limited number of mitotic divisions. Porcine epidermal stem cells, located in the bulge region of the outer root sheath of hair follicles, migrate in vitro from hair sheaths and because they are resistant to anoikis (detachment induced apoptosis), survive in non-adhesive conditions to form spheroids. These cells express keratins, galectin-1 and their nuclei are rich in DeltaNp63alpha. Interestingly, the multiple phenotype analysis of the human tumor cells in squamous carcinoma of head and neck revealed similarities with epidermal stem cells. These cancer stem cells are usually located on the periphery of the tumor where the invasive front of the tumor responsible for its aggressive behavior is located. In contrast, extensive expression of markers of terminal differentiation such as expression of glycoligands reactive for the endogenous lectin, galectin-3, indicates better tumor prognosis.
- MeSH
- epidermis cytologie MeSH
- financování organizované MeSH
- galektin 1 metabolismus MeSH
- hojení ran MeSH
- keratiny metabolismus MeSH
- kmenové buňky fyziologie MeSH
- lidé MeSH
- mitóza MeSH
- nádory hlavy a krku terapie MeSH
- prasata MeSH
- transplantace kmenových buněk MeSH
- viabilita buněk MeSH
- vlasový folikul cytologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
The cell-cycle regulating gene, p16INK4A, encoding an inhibitor of cyclin-dependent kinases 4 and 6, is considered to play an important role in cellular aging and in premature senescence. Although there is an age-dependent increase of p16INK4A expression in human fibroblast senescence in vitro, no data are available regarding the age dependency of p16INK4A in vivo. To determine whether p16INK4A expression in human skin correlates with donor age, p16INK4A expression was analyzed by immunohistochemistry as well as the expression of the p16INK4A repressor BMI1. Samples from the age groups 0-20, 21-70, and 71-95 years were selected from a bank of healthy human skin. We show that the number of p16INK4A positive cells is significantly higher in elderly individuals compared to the younger age groups. The number of p16INK4A positive cells was found to be increased in both epidermis and dermis, compartments with strictly different proliferative activities. BMI1 gene expression was significantly down-regulated with increasing donor age, whereas no striking age differences were observed for Ki67. In immunofluorescence co-expression studies, Ki67-positive cells were negative for p16INK4A and BMI1-expressing cells also stained negatively for Ki67. In conclusion, we provide for the first time evidence that p16INK4A expression directly correlates with chronological aging of human skin in vivo. p16INK4A therefore is a biomarker for human aging in vivo. The data reported here suggest a model for changes in regulatory gene expression that drive aging in human skin.
- MeSH
- antigen Ki-67 metabolismus MeSH
- biologické markery * MeSH
- buněčné dělení MeSH
- epidermis cytologie metabolismus MeSH
- fluorescenční barviva MeSH
- imunohistochemie MeSH
- indoly MeSH
- inhibitor p16 cyklin-dependentní kinasy genetika metabolismus MeSH
- jaderné proteiny genetika metabolismus MeSH
- kůže * metabolismus MeSH
- lidé MeSH
- PRC1 MeSH
- protoonkogenní proteiny genetika metabolismus MeSH
- regulace genové exprese * fyziologie MeSH
- represorové proteiny genetika metabolismus MeSH
- škára metabolismus MeSH
- stárnutí buněk * fyziologie MeSH
- věkové rozložení MeSH
- Check Tag
- lidé MeSH
BACKGROUND AND OBJECTIVE: Because the nucleolar protein nucleostemin is present in bone marrow and neuronal stem cells and malignancies originating thereof we monitored its expression in frozen sections from normal human epidermis, basal cell carcinomas, cultured keratinocytes and cells of the squamous carcinoma line FaDu. In addition, probing the value of this protein as a marker of epidermal stem cells was an aim of this study. MATERIALS AND METHODS: To further characterize cell features we added analysis of expression of keratins 10 or 19 as markers of terminal differentiation and Ki67 as marker of proliferating cells as well as three adhesion/growth-regulatory galectins. RESULTS: Immunohistochemical monitoring revealed expression of nucleostemin in cells of both Ki67-positive and -negative nuclei regardless of the K10-expression status. Cultured keratinocytes were positive, when they were prepared from hair follicles and cultured in the presence of feeder cells. A small population of these nucleostemin-positive cells also expressed galectin-1 but not galectins-3 and -9 in their nucleoli. Part of these cells also expressed keratin 19. FaDu cells were strongly positive, illustrating expression in malignant cells which require no feeder layer. Of note, the number of galectin-1-positive nucleoli was reduced in the course of culture. CONCLUSION: Nucleostemin positivity cannot be considered as marker for stem cells in skin sections. In cultured cells, nucleostemin is expressed in a distinct population of the epidermal cells from hair follicle kept in the presence of a feeder layer, intimating an association of nucleostemin expression with this type of epithelio-mesenchymal interaction which is not essential during propagation of malignant cells
- MeSH
- antigen Ki-67 genetika metabolismus MeSH
- bazocelulární karcinom genetika metabolismus patologie MeSH
- biologické markery metabolismus MeSH
- epidermis cytologie metabolismus patologie MeSH
- financování organizované MeSH
- galektiny genetika metabolismus MeSH
- imunohistochemie MeSH
- jaderné proteiny metabolismus MeSH
- keratin-10 genetika metabolismus MeSH
- keratin-9 genetika metabolismus MeSH
- kmenové buňky cytologie metabolismus patologie MeSH
- kultivované buňky MeSH
- lidé MeSH
- nádorové buňky kultivované MeSH
- nádory kůže genetika metabolismus patologie MeSH
- regulace genové exprese u nádorů genetika MeSH
- regulace genové exprese imunologie MeSH
- spinocelulární karcinom genetika metabolismus patologie MeSH
- transportní proteiny metabolismus MeSH
- Check Tag
- lidé MeSH