stem cells
Dotaz
Zobrazit nápovědu
Signal Transducer and Activator of Transcription 3 (STAT3) is a transcription factor with many important functions in the biology of normal and transformed cells. Its regulation is highly complex as it is involved in signaling pathways in many different cell types and under a wide variety of conditions. Besides other functions, STAT3 is an important regulator of normal stem cells and cancer stem cells. p63 which is a member of the p53 protein family is also involved in these functions and is both physically and functionally connected with STAT3. This review summarizes STAT3 function and regulation, its role in stem cell and cancer stem cell properties and highlights recent reports about its relationship to p63.
- Klíčová slova
- Cancer stem cells, STAT3, Stem cells, p63,
- MeSH
- fosforylace MeSH
- lidé MeSH
- lidské embryonální kmenové buňky metabolismus MeSH
- metylace MeSH
- mikro RNA metabolismus MeSH
- myší embryonální kmenové buňky metabolismus MeSH
- myši MeSH
- nádorové kmenové buňky metabolismus MeSH
- nádorové supresorové proteiny chemie metabolismus MeSH
- nádory metabolismus MeSH
- přeprogramování buněk MeSH
- transkripční faktor STAT3 chemie metabolismus MeSH
- transkripční faktory chemie metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- mikro RNA MeSH
- nádorové supresorové proteiny MeSH
- TP63 protein, human MeSH Prohlížeč
- transkripční faktor STAT3 MeSH
- transkripční faktory MeSH
UNLABELLED: Stem cell-based therapy has become an attractive and promising approach for the treatment of severe injuries or thus-far incurable diseases. However, the use of stem cells is often limited by a shortage of available tissue-specific stem cells; therefore, other sources of stem cells are being investigated and tested. In this respect, mesenchymal stromal/stem cells (MSCs) have proven to be a promising stem cell type. In the present study, we prepared MSCs from bone marrow (BM-MSCs) or adipose tissue (Ad-MSCs) as well as limbal epithelial stem cells (LSCs), and their growth, differentiation, and secretory properties were compared. The cells were grown on nanofiber scaffolds and transferred onto the alkali-injured eye in a rabbit model, and their therapeutic potential was characterized. We found that BM-MSCs and tissue-specific LSCs had similar therapeutic effects. Clinical characterization of the healing process, as well as the evaluation of corneal thickness, re-epithelialization, neovascularization, and the suppression of a local inflammatory reaction, were comparable in the BM-MSC- and LSC-treated eyes, but results were significantly better than in injured, untreated eyes or in eyes treated with a nanofiber scaffold alone or with a nanofiber scaffold seeded with Ad-MSCs. Taken together, the results show that BM-MSCs' therapeutic effect on healing of injured corneal surface is comparable to that of tissue-specific LSCs. We suggest that BM-MSCs can be used for ocular surface regeneration in cases when autologous LSCs are absent or difficult to obtain. SIGNIFICANCE: Damage of ocular surface represents one of the most common causes of impaired vision or even blindness. Cell therapy, based on transplantation of stem cells, is an optimal treatment. However, if limbal stem cells (LSCs) are not available, other sources of stem cells are tested. Mesenchymal stem cells (MSCs) are a convenient type of cell for stem cell therapy. The therapeutic potential of LSCs and MSCs was compared in an experimental model of corneal injury, and healing was observed following chemical injury. MSCs and tissue-specific LSCs had similar therapeutic effects. The results suggest that bone marrow-derived MSCs can be used for ocular surface regeneration in cases when autologous LSCs are absent or difficult to obtain.
- Klíčová slova
- Alkali-injured ocular surface, Corneal regeneration, Limbal stem cells, Mesenchymal stem cells, Stem cell-based therapy,
- MeSH
- biologické markery metabolismus MeSH
- buněčná a tkáňová terapie metody MeSH
- buněčná diferenciace MeSH
- buňky kostní dřeně cytologie fyziologie MeSH
- chemické popálení patologie terapie MeSH
- epitelové buňky cytologie fyziologie transplantace MeSH
- exprese genu MeSH
- fyziologická neovaskularizace MeSH
- králíci MeSH
- limbus corneae krevní zásobení zranění MeSH
- mezenchymální kmenové buňky cytologie fyziologie MeSH
- primární buněčná kultura MeSH
- proliferace buněk MeSH
- reepitalizace fyziologie MeSH
- rohovkový epitel krevní zásobení zranění MeSH
- tkáňové podpůrné struktury MeSH
- transplantace mezenchymálních kmenových buněk * MeSH
- tuková tkáň cytologie fyziologie MeSH
- tukové buňky cytologie fyziologie MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Názvy látek
- biologické markery MeSH
Neural differentiation of human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) can produce a valuable and robust source of human neural cell subtypes, holding great promise for the study of neurogenesis and development, and for treating neurological diseases. However, current hESCs and hiPSCs neural differentiation protocols require either animal factors or embryoid body formation, which decreases efficiency and yield, and strongly limits medical applications. Here we develop a simple, animal-free protocol for neural conversion of both hESCs and hiPSCs in adherent culture conditions. A simple medium formula including insulin induces the direct conversion of >98% of hESCs and hiPSCs into expandable, transplantable, and functional neural progenitors with neural rosette characteristics. Further differentiation of neural progenitors into dopaminergic and spinal motoneurons as well as astrocytes and oligodendrocytes indicates that these neural progenitors retain responsiveness to instructive cues revealing the robust applicability of the protocol in the treatment of different neurodegenerative diseases. The fact that this protocol includes animal-free medium and human extracellular matrix components avoiding embryoid bodies makes this protocol suitable for the use in clinic. Stem Cells Translational Medicine 2017;6:1217-1226.
- Klíčová slova
- Cellular therapy, Clinical translation, Differentiation, Embryonic stem cells, Induced pluripotent stem cells, Neural differentiation, Pluripotent stem cells,
- MeSH
- buněčná a tkáňová terapie MeSH
- buněčná diferenciace fyziologie MeSH
- embryonální kmenové buňky fyziologie MeSH
- indukované pluripotentní kmenové buňky cytologie MeSH
- kultivované buňky MeSH
- lidé MeSH
- pluripotentní kmenové buňky cytologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Nowadays, regenerative and reparative medicine has grown in popularity. Dental stem cells are easily accessible source of adult stem cells. They can be harvested by a tooth extraction or spontaneous deciduous tooth exfoliation. They have to be isolated, expanded and stored until time they would be needed for individual stem cell therapy. Cryopreservation is both a short-term and long-term storage of tissues or cells at sub-zero temperatures. There are several methods of cryopreservation requiring different technologies. The objective of this review is to compare them and highlight their advantages and disadvantages.
- Klíčová slova
- cryopreservation, dental stem cells, freezing protocol,
- MeSH
- dospělé kmenové buňky cytologie MeSH
- extrakce zubů MeSH
- kryoprezervace metody MeSH
- lidé MeSH
- regenerativní lékařství MeSH
- transplantace kmenových buněk * MeSH
- vitrifikace * MeSH
- vypadávání zubů MeSH
- zubní dřeň cytologie MeSH
- zuby mléčné cytologie MeSH
- zuby cytologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Transgenic mice expressing green fluorescent protein (GFP) are useful in transplantation experiments. When we used ubiquitin-GFP (UBC-GFP) transgenic mice to study the availability of niches for transplanted hematopoietic stem and progenitor cells, the results were strikingly different from the corresponding experiments that used congenic mice polymorphic in the CD45 antigen. Analysis of these unexpected results revealed that the hematopoiesis of UBC-GFP mice was outcompeted by the hematopoiesis of wild-type (WT) mice. Importantly, UBC-GFP mice engrafted the transplanted bone marrow of WT mice without conditioning. There was a significant bias toward lymphopoiesis in the WT branch of chimeric UBC-GFP/WT hematopoiesis. A fraction of immature Sca-1+ cells in the spleen of UBC-GFP mice expressed GFP at a very high level. The chimeric hematopoiesis was stable in the long term and also after transplantation to secondary recipient mice. The article thus identifies a specific defect in the hematopoiesis of UBC-GFP transgenic mice that compromises the lymphoid-primed hematopoietic stem cells in the bone marrow and spleen. Stem Cells 2018;36:1237-1248.
- Klíčová slova
- Bone marrow transplantation, Cell competition, Extramedullary hematopoiesis, Green fluorescent protein, Hematopoiesis, Lymphopoiesis, Stem cell niche, Stem cells, Transgenic mouse,
- MeSH
- chiméra MeSH
- hematopoetické kmenové buňky metabolismus MeSH
- hematopoéza MeSH
- kostní dřeň metabolismus MeSH
- lymfocyty metabolismus MeSH
- lymfopoéza MeSH
- myši inbrední C57BL MeSH
- myši transgenní MeSH
- slezina metabolismus MeSH
- splenektomie MeSH
- thymus metabolismus MeSH
- transplantace hematopoetických kmenových buněk * MeSH
- ubikvitin metabolismus MeSH
- zelené fluorescenční proteiny metabolismus MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- ubikvitin MeSH
- zelené fluorescenční proteiny MeSH
Epithelial-mesenchymal transition (EMT) is a crucial process with significance in the metastasis of malignant tumors. It is through the acquisition of plasticity that cancer cells become more mobile and gain the ability to metastasize to other tissues. The mesenchymal-epithelial transition (MET) is the return to an epithelial state, which allows for the formation of secondary tumors. Both processes, EMT and MET, are regulated by different pathways and different mediators, which affects the sophistication of the overall tumorigenesis process. Not insignificant are also cancer stem cells and their participation in the angiogenesis, which occur very intensively within tumors. Difficulties in effectively treating cancer are primarily dependent on the potential of cancer cells to rapidly expand and occupy secondarily vital organs. Due to the ability of these cells to spread, the concept of the circulating tumor cell (CTC) has emerged. Interestingly, CTCs exhibit molecular diversity and stem-like and mesenchymal features, even when derived from primary tumor tissue from a single patient. While EMT is necessary for metastasis, MET is required for CTCs to establish a secondary site. A thorough understanding of the processes that govern the balance between EMT and MET in malignancy is crucial.
- Klíčová slova
- Cancer stem Cells, Circulating Tumor cell (CTC), Epithelial-mesenchymal Transition (EMT), Mesenchymal-epithelial Transition (MET),
- MeSH
- epitelo-mezenchymální tranzice * MeSH
- fenotyp MeSH
- kmenové buňky metabolismus cytologie patologie MeSH
- lidé MeSH
- nádorové cirkulující buňky * patologie metabolismus MeSH
- nádorové kmenové buňky * patologie metabolismus MeSH
- nádory patologie metabolismus MeSH
- patologická angiogeneze * patologie MeSH
- proliferace buněk genetika MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
Stem cells can be defined as units of biological organization that are responsible for the development and the regeneration of organ and tissue systems. They are able to renew their populations and to differentiate into multiple cell lineages. Therefore, these cells have great potential in advanced tissue engineering and cell therapies. When seeded on synthetic or nature-derived scaffolds in vitro, stem cells can be differentiated towards the desired phenotype by an appropriate composition, by an appropriate architecture, and by appropriate physicochemical and mechanical properties of the scaffolds, particularly if the scaffold properties are combined with a suitable composition of cell culture media, and with suitable mechanical, electrical or magnetic stimulation. For cell therapy, stem cells can be injected directly into damaged tissues and organs in vivo. Since the regenerative effect of stem cells is based mainly on the autocrine production of growth factors, immunomodulators and other bioactive molecules stored in extracellular vesicles, these structures can be isolated and used instead of cells for a novel therapeutic approach called "stem cell-based cell-free therapy". There are four main sources of stem cells, i.e. embryonic tissues, fetal tissues, adult tissues and differentiated somatic cells after they have been genetically reprogrammed, which are referred to as induced pluripotent stem cells (iPSCs). Although adult stem cells have lower potency than the other three stem cell types, i.e. they are capable of differentiating into only a limited quantity of specific cell types, these cells are able to overcome the ethical and legal issues accompanying the application of embryonic and fetal stem cells and the mutational effects associated with iPSCs. Moreover, adult stem cells can be used in autogenous form. These cells are present in practically all tissues in the organism. However, adipose tissue seems to be the most advantageous tissue from which to isolate them, because of its abundancy, its subcutaneous location, and the need for less invasive techniques. Adipose tissue-derived stem cells (ASCs) are therefore considered highly promising in present-day regenerative medicine.
- Klíčová slova
- Adult stem cells, Cell differentiation, Cell therapy, Clinical application, Embryonic stem cells, Extracellular vesicles, Fetal stem cells, Induced pluripotent stem cells, Multipotent cells, Progenitor cells, Regenerative medicine, Tissue engineering, Totipotent cells,
- MeSH
- buněčná diferenciace MeSH
- kmenové buňky * cytologie fyziologie MeSH
- lidé MeSH
- myši MeSH
- regenerativní lékařství * MeSH
- tkáňové inženýrství * MeSH
- transplantace kmenových buněk * MeSH
- tuková tkáň cytologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Induced pluripotent stem (iPS) cells are derived from differentiated cells by different reprogramming techniques, by introducing specific transcription factors responsible for pluripotency. Induced pluripotent stem cells can serve as an excellent source for differentiated neural stem/progenitor cells (NSCs/NPs). Several methods and protocols are utilized to create a robust number of NSCs/NPs without jeopardizing the safety issues required for in vivo applications. A variety of disease-specific iPS cells have been used to study nervous system diseases. In this chapter, we will focus on some of the derivation and differentiation approaches and the application of iPS-NPs in the treatment of spinal cord injury and stroke.
- Klíčová slova
- Induced pluripotent stem cells, Neural stem cells, Neuronal differentiation, Spinal cord injury, Stroke,
- MeSH
- buněčná diferenciace * MeSH
- cévní mozková příhoda patologie terapie MeSH
- indukované pluripotentní kmenové buňky cytologie MeSH
- lidé MeSH
- modely neurologické * MeSH
- nervové kmenové buňky cytologie MeSH
- poranění míchy patologie terapie MeSH
- přeprogramování buněk MeSH
- transkripční faktory metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- transkripční faktory MeSH
The successful development and characterization of human induced pluripotent stem cells (iPSCs) provides a powerful tool to study the molecular mechanisms that control cell fate decisions and differentiation toward distinct lineages. Here we focus on the ability of donors derived iPSCs to differentiate toward hematopoietic progenitor cells and on the analysis of their telomere length. The ability to screen telomere length in individual donors is important for defining cellular senescence, which correlates with their differentiation potential toward hematopoietic lineages. We have modified iPSC culture protocol and telomere length analysis to suit for high throughput screening of telomere length in large number of individual donors. This approach can be used to demonstrate the heterogeneity or changes of telomere length and its shortening as an exclusion criterion for selection of suitable donors for future stem cell therapies.
- Klíčová slova
- Cellular senescence, Hematopoiesis, Hematopoietic stem cells, Induced pluripotent stem cells, Telomere length,
- MeSH
- biologické markery * MeSH
- buněčné kultury * MeSH
- čipová analýza tkání metody MeSH
- hematopoetické kmenové buňky cytologie metabolismus MeSH
- indukované pluripotentní kmenové buňky cytologie metabolismus MeSH
- lidé MeSH
- rychlé screeningové testy * MeSH
- stárnutí buněk * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- biologické markery * MeSH
Human pluripotent stem cells have the potential to change the way in which human diseases are cured. Clinical-grade human embryonic stem cells and human induced pluripotent stem cells have to be created according to current good manufacturing practices and regulations. Quality and safety must be of the highest importance when humans' lives are at stake. With the rising number of clinical trials, there is a need for a consensus on hPSCs characterization. Here, we summarize mandatory and 'for information only' characterization methods with release criteria for the establishment of clinical-grade hPSC lines.
- Klíčová slova
- cGMP, cell therapy, characterization, clinical, hESC, hPSCs, hiPSC, human embryonic stem cells, human induced pluripotent stem cells, human pluripotent stem cells,
- MeSH
- Bacteria MeSH
- buněčná a tkáňová terapie metody MeSH
- endotoxiny MeSH
- indukované pluripotentní kmenové buňky MeSH
- lidé MeSH
- lidské embryonální kmenové buňky MeSH
- Mycoplasma MeSH
- pluripotentní kmenové buňky * MeSH
- viry MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- endotoxiny MeSH