Human induced pluripotent stem cell-derived neural stem/progenitor cells are used in cell-replacement and regenerative therapeutic strategies after traumatic central nervous system injury. Traumatic injury alters the host microenvironment, which in turn affects the functionality of transplanted human neural stem/ progenitor cells and potentially limits their benefits for neurorepair. However, the underlying mechanisms through which the host environment alters the fate and functionality of transplanted human neural stem/progenitor cells remain poorly understood. Here, we showed that massive deposition of blood-derived fibrinogen in a mouse model of spinal cord injury contributed to an altered lesion environment. Fibrinogen promoted human neural stem/progenitor cell differentiation into reactive astrocytes by activating the BMP receptor signaling pathway and inducing of the transcriptional regulator inhibitor of DNA binding 3. ID3 -depleted human neural stem/progenitor cells, generated by CRISPR/Cas9-mediated genome editing, reduced astrocyte formation in response to astrogenic stimuli. Instead, ID3 -depleted human neural stem/progenitor cells had a bipolar, immature glial progenitor cell phenotype. These modified cells secreted extracellular vesicles with a distinct miRNA profile that enhanced neurite outgrowth. We conclude that targeting inhibitor of DNA binding 3 in human neural stem/progenitor cells can beneficially modulate their functionality and cell fate in the injured central nervous system toward glial progenitor cells, potentially enhancing their capacity to promote central nervous system repair.

• Klíčová slova
• CRISPR-Cas9, astrocyte, extracellular vesicles, fibrinogen, human iPSC-derived neural stem/progenitor cell, inhibitor of DNA binding 3 (ID3), microRNA, nerve regeneration, neurite outgrowth, spinal cord,
• Publikační typ
• časopisecké články MeSH

DISP3 (PTCHD2), a sterol-sensing domain-containing protein, is highly expressed in neural tissue but its role in neural differentiation is unknown. In the present study we used a multipotent cerebellar progenitor cell line, C17.2, to investigate the impact of DISP3 on the proliferation and differentiation of neural precursors. We found that ectopically expressed DISP3 promotes cell proliferation and alters expression of genes that are involved in tumorigenesis. Finally, the differentiation profile of DISP3-expressing cells was altered, as evidenced by delayed expression of neural specific markers and a reduced capacity to undergo neural differentiation.

• Klíčová slova
• Cancer, Differentiation, Lipids, Neural cells, Proliferation,
• MeSH
• buněčná diferenciace * MeSH
• buněčné linie MeSH
• lidé MeSH
• membránové proteiny genetika   metabolismus   MeSH
• metabolismus lipidů MeSH
• mozek cytologie   MeSH
• nervové kmenové buňky cytologie   metabolismus   MeSH
• proliferace buněk MeSH
• regulace genové exprese MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• DISP3 protein, human MeSH Prohlížeč
• membránové proteiny MeSH

Despite therapeutic advances, neurodegenerative diseases and disorders remain some of the leading causes of mortality and morbidity in the United States. Therefore, cell-based therapies to replace lost or damaged neurons and supporting cells of the central nervous system (CNS) are of great therapeutic interest. To that end, human pluripotent stem cell (hPSC) derived neural progenitor cells (hNPCs) and their neuronal derivatives could provide the cellular 'raw material' needed for regenerative medicine therapies for a variety of CNS disorders. In addition, hNPCs derived from patient-specific hPSCs could be used to elucidate the underlying mechanisms of neurodegenerative diseases and identify potential drug candidates. However, the scientific and clinical application of hNPCs requires the development of robust, defined, and scalable substrates for their long-term expansion and neuronal differentiation. In this study, we rationally designed a vitronectin-derived peptide (VDP) that served as an adhesive growth substrate for the long-term expansion of several hNPC lines. Moreover, VDP-coated surfaces allowed for the directed neuronal differentiation of hNPC at levels similar to cells differentiated on traditional extracellular matrix protein-based substrates. Overall, the ability of VDP to support the long-term expansion and directed neuronal differentiation of hNPCs will significantly advance the future translational application of these cells in treating injuries, disorders, and diseases of the CNS.

• Klíčová slova
• Defined conditions, Human neural progenitor cells, Human pluripotent stem cells, Peptide,
• MeSH
• biokompatibilní potahované materiály farmakologie   MeSH
• buněčná adheze účinky léků   MeSH
• buněčná diferenciace účinky léků   MeSH
• extracelulární matrix - proteiny metabolismus   MeSH
• lidé MeSH
• molekuly buněčné adheze metabolismus   MeSH
• myši MeSH
• nervové kmenové buňky cytologie   účinky léků   metabolismus   MeSH
• neurony cytologie   účinky léků   metabolismus   MeSH
• peptidy farmakologie   MeSH
• pluripotentní kmenové buňky cytologie   účinky léků   metabolismus   MeSH
• proliferace buněk účinky léků   MeSH
• vitronektin farmakologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• biokompatibilní potahované materiály MeSH
• extracelulární matrix - proteiny MeSH
• molekuly buněčné adheze MeSH
• peptidy MeSH
• vitronektin MeSH

Wnt signaling plays an important role in the self-renewal, fate-commitment and survival of the neural stem/progenitor cells (NS/PCs) of the adult central nervous system (CNS). Ischemic stroke impairs the proper functioning of the CNS and, therefore, active Wnt signaling may prevent, ameliorate, or even reverse the negative effects of ischemic brain injury. In this review, we provide the current knowledge of Wnt signaling in the adult CNS, its status in diverse cell types, and the Wnt pathway's impact on the properties of NS/PCs and glial cells in the context of ischemic injury. Finally, we summarize promising strategies that might be considered for stroke therapy, and we outline possible future directions of the field.

• Klíčová slova
• Wnt signaling, adult neurogenesis, central nervous system, glia, ischemia, neural stem/progenitor cell, stroke, subgranular zone, subventricular zone,
• MeSH
• buněčná diferenciace genetika   MeSH
• cílená molekulární terapie metody   trendy   MeSH
• dospělí MeSH
• ischemie mozku genetika   metabolismus   patologie   patofyziologie   MeSH
• lidé MeSH
• mozek cytologie   patologie   fyziologie   MeSH
• nervové kmenové buňky patologie   fyziologie   MeSH
• neurogeneze fyziologie   MeSH
• neuroglie patologie   fyziologie   MeSH
• signální dráha Wnt genetika   fyziologie   MeSH
• tranzitorní ischemická ataka genetika   metabolismus   patologie   terapie   MeSH
• zdraví MeSH
• zvířata MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Notch and gp130 signaling are involved in the regulation of multiple cellular processes across various tissues during animal ontogenesis. In the developing nervous system, both signaling pathways intervene at many stages to determine cell fate-from the first neural lineage commitment and generation of neuronal precursors, to the terminal specification of cells as neurons and glia. In most cases, the effects of Notch and gp130 signaling in these processes are similar. The aim of the current review was to summarize the knowledge regarding the roles of Notch and gp130 signaling in the maintenance of neural stem and progenitor cells during animal ontogenesis, from early embryo to adult. Recent data show a direct crosstalk between these signaling pathways that seems to be specific for a particular type of neural progenitors.

• MeSH
• cytokinový receptor gp130 metabolismus   MeSH
• interakce mezi receptory a ligandy MeSH
• lidé MeSH
• nervové kmenové buňky metabolismus   MeSH
• neurogeneze MeSH
• receptory Notch metabolismus   MeSH
• signální transdukce * MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• cytokinový receptor gp130 MeSH
• receptory Notch MeSH

Neural crest (NC) is a transient embryonic tissue, whose cells are motile and multipotent until they reach their destination and differentiate according to microenvironmental cues into a variety of cell types. However, a subpopulation of these cells remains multipotent. They were found, among other locations, in a bulge of adult murine whisker follicle and were designated epidermal neural crest stem cells (EPI-NCSCs). The aim of this work is to ascertain whether the EPI-NCSCs could be isolated from human hair follicles as well. Due to their exceptional properties, they could represent potential candidates for stem cell therapy. The presented work focuses on the isolation and characterization of EPI-NCSCs from human skin. We obtained a population of cells that expressed markers of NC, NC progeny and general stem cell markers. After prolonged cultivation, the subpopulation of cells spontaneously differentiated into some of NC derivatives, i.e. neurons, smooth muscle cells and Schwann cell progenitors. Targeted differentiation with neuregulin 1 highly increased the number of Schwann cells in the culture. Human EPI-NCSCs could also grow under non-adherent conditions and form 3-dimensional spheres. Microarray analysis was performed and gene profile of human EPI-NCSCs was compared with the list of key genes of murine EPI-NCSCs and the list of genes up-regulated in newly induced NC cells. This revealed 94% and 88% similarity, respectively. All presented results strongly support the NCSC identity and multipotency of isolated human cells. These cells could thus be used in regenerative medicine, especially because of the easy accessibility of donor tissue.

• MeSH
• buněčná diferenciace MeSH
• crista neuralis cytologie   metabolismus   MeSH
• imunohistochemie MeSH
• kmenové buňky cytologie   metabolismus   MeSH
• kultivované buňky MeSH
• lidé MeSH
• multipotentní kmenové buňky cytologie   metabolismus   MeSH
• myši MeSH
• neurony MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• Schwannovy buňky MeSH
• sekvenční analýza hybridizací s uspořádaným souborem oligonukleotidů MeSH
• stanovení celkové genové exprese MeSH
• transplantace kmenových buněk MeSH
• vibrissae cytologie   MeSH
• vlasový folikul cytologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem 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

Both gain- and loss-of-function mutations have recently implicated HCFC1 in neurodevelopmental disorders. Here, we extend our previous HCFC1 over-expression studies by employing short hairpin RNA to reduce the expression of Hcfc1 in embryonic neural cells. We show that in contrast to over-expression, loss of Hcfc1 favoured proliferation of neural progenitor cells at the expense of differentiation and promoted axonal growth of post-mitotic neurons. To further support the involvement of HCFC1 in neurological disorders, we report two novel HCFC1 missense variants found in individuals with intellectual disability (ID). One of these variants, together with three previously reported HCFC1 missense variants of unknown pathogenicity, were functionally assessed using multiple cell-based assays. We show that three out of the four variants tested result in a partial loss of HCFC1 function. While over-expression of the wild-type HCFC1 caused reduction in HEK293T cell proliferation and axonal growth of neurons, these effects were alleviated upon over-expression of three of the four HCFC1 variants tested. One of these partial loss-of-function variants disrupted a nuclear localization sequence and the resulting protein displayed reduced ability to localize to the cell nucleus. The other two variants displayed negative effects on the expression of the HCFC1 target gene MMACHC, which is responsible for the metabolism of cobalamin, suggesting that these individuals may also be susceptible to cobalamin deficiency. Together, our work identifies plausible cellular consequences of missense HCFC1 variants and identifies likely and relevant disease mechanisms that converge on embryonic stages of brain development.

• MeSH
• aktivní transport - buněčné jádro MeSH
• buněčná diferenciace genetika   MeSH
• exprese genu MeSH
• faktor C1 hostitelské buňky chemie   genetika   metabolismus   MeSH
• HEK293 buňky MeSH
• kultivované buňky MeSH
• lidé MeSH
• malá interferující RNA genetika   MeSH
• mentální retardace genetika   MeSH
• mozek cytologie   embryologie   MeSH
• mutace * MeSH
• myši MeSH
• nervové kmenové buňky cytologie   metabolismus   MeSH
• oxidoreduktasy MeSH
• proliferace buněk MeSH
• RNA interference MeSH
• rodokmen MeSH
• sekvence aminokyselin MeSH
• substituce aminokyselin MeSH
• transdukce genetická MeSH
• transportní proteiny genetika   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• faktor C1 hostitelské buňky MeSH
• malá interferující RNA MeSH
• MMACHC protein, human MeSH Prohlížeč
• oxidoreduktasy MeSH
• transportní proteiny MeSH

Previously, a new biodegradable poly(ester urethane urea) was synthesized based on polycaprolactone-diol and fish gelatin (PU-Gel). In this work, the potential of this new material for neural tissue engineering is evaluated. Membranes with randomly oriented fibers and with aligned fibers are produced using electrospinning and characterized regarding their mechanical behavior under both dry and wet conditions. Wet samples exhibit a lower Young's modulus than dry ones and aligned membranes are stiffer and more brittle than those randomly oriented. Cyclic tensile tests are conducted and high values for recovery ratio and resilience are obtained. Both membranes exhibited a hydrophobic surface, measured by the water contact angle (WCA). Human mesenchymal stem cells from umbilical cord tissue (UC-MSCs) and human neural stem cells (NSCs) are seeded on both types of membranes, which support their adhesion and proliferation. Cells stained for the cytoskeleton and nucleus in membranes with aligned fibers display an elongated morphology following the alignment direction. As the culture time increased, higher cell viability is obtained on randomfibers for UC-MSCs while no differences are observed for NSCs. The membranes support neuronal differentiation of NSCs, as evidenced by markers for a neuronal filament protein (NF70) and for a microtubule-associated protein (MAP2).

• Klíčová slova
• electrospinning, gelatin, mesenchymal stem cells, neural stem cells, poly(ester urethane urea),
• MeSH
• biokompatibilní materiály chemie   farmakologie   MeSH
• buněčná adheze účinky léků   MeSH
• buněčná diferenciace účinky léků   MeSH
• kultivované buňky MeSH
• lidé MeSH
• mezenchymální kmenové buňky * cytologie   účinky léků   metabolismus   MeSH
• nervové kmenové buňky * cytologie   účinky léků   metabolismus   MeSH
• pevnost v tahu MeSH
• polyestery * chemie   farmakologie   MeSH
• polyurethany * chemie   farmakologie   MeSH
• proliferace buněk účinky léků   MeSH
• testování materiálů MeSH
• tkáňové inženýrství * metody   MeSH
• tkáňové podpůrné struktury chemie   MeSH
• viabilita buněk účinky léků   MeSH
• želatina * chemie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• biokompatibilní materiály MeSH
• poly(ester urethane)urea MeSH Prohlížeč
• polyestery * MeSH
• polyurethany * MeSH
• želatina * 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