Ependymal cells, a dormant population of ciliated progenitors found within the central canal of the spinal cord, undergo significant alterations after spinal cord injury (SCI). Understanding the molecular events that induce ependymal cell activation after SCI represents the first step toward controlling the response of the endogenous regenerative machinery in damaged tissues. This response involves the activation of specific signaling pathways in the spinal cord that promotes self-renewal, proliferation, and differentiation. We review our current understanding of the signaling pathways and molecular events that mediate the SCI-induced activation of ependymal cells by focusing on the roles of some cell adhesion molecules, cellular membrane receptors, ion channels (and their crosstalk), and transcription factors. An orchestrated response regulating the expression of receptors and ion channels fine-tunes and coordinates the activation of ependymal cells after SCI or cell transplantation. Understanding the major players in the activation of ependymal cells may help us to understand whether these cells represent a critical source of cells contributing to cellular replacement and tissue regeneration after SCI. A more complete understanding of the role and function of individual signaling pathways in endogenous spinal cord progenitors may foster the development of novel targeted therapies to induce the regeneration of the injured spinal cord.

• Klíčová slova
• Activation, Ependymal cells, Regeneration, Spinal cord injury,
• MeSH
• ependym metabolismus   MeSH
• iontové kanály metabolismus   MeSH
• lidé MeSH
• mícha MeSH
• neuroglie metabolismus   MeSH
• poranění míchy * terapie   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• iontové kanály MeSH

Spinal cord injury is a devastating medical condition with no effective treatment. One approach to SCI treatment may be provided by stem cells (SCs). Studies have mainly focused on the transplantation of exogenous SCs, but the induction of endogenous SCs has also been considered as an alternative. While the differentiation potential of neural stem cells in the brain neurogenic regions has been known for decades, there are ongoing debates regarding the multipotent differentiation potential of the ependymal cells of the central canal in the spinal cord (SCECs). Following spinal cord insult, SCECs start to proliferate and differentiate mostly into astrocytes and partly into oligodendrocytes, but not into neurons. However, there are several approaches concerning how to increase neurogenesis in the injured spinal cord, which are discussed in this review. The potential treatment approaches include drug administration, the reduction of neuroinflammation, neuromodulation with physical factors and in vivo reprogramming.

• Klíčová slova
• astrocytes, ependymal stem cells, growth factors, neurogenesis, neuroinflammation, physical factors, reprogramming, spinal canal, spinal cord injury, valproic acid,
• MeSH
• buněčná diferenciace MeSH
• lidé MeSH
• mícha MeSH
• nervové kmenové buňky * MeSH
• neurogeneze MeSH
• neurony MeSH
• poranění míchy * terapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Oligodendrocyte progenitor cells (OPCs) play a pivotal role in both health and disease within the central nervous system, with oligodendrocytes, arising from resident OPCs, being the main myelinating cell type. Disruption in OPC numbers can lead to various deleterious health defects. Numerous studies have described techniques for isolating OPCs to obtain a better understanding of this cell type and to open doors for potential treatments of injury and disease. However, the techniques used in the majority of these studies involve several steps and are time consuming, with current culture protocols using serum and embryonic or postnatal cortical tissue as a source of isolation. We present a primary culture method for the direct isolation of functional adult rat OPCs, identified by neuron-glial antigen 2 (NG2) and platelet derived growth factor receptor alpha (PDGFrα) expression, which can be obtained from the adult spinal cord. Our method uses a simple serum-free cocktail of 3 growth factors - FGF2, PDGFAA, and IGF-I, to expand adult rat OPCs in vitro to 96% purity. Cultured cells can be expanded for at least 10 passages with very little manipulation and without losing their phenotypic progenitor cell properties, as shown by immunocytochemistry and RT-PCR. Cultured adult rat OPCs also maintain their ability to differentiate into GalC positive cells when incubated with factors known to stimulate their differentiation. This new isolation method provides a new source of easily accessible adult stem cells and a powerful tool for their expansion in vitro for studies aimed at central nervous system repair.

• Klíčová slova
• Adult spinal cord, CNS, Differentiation, Progenitor cells, Spinal cord injury,
• MeSH
• antigeny metabolismus   MeSH
• destičkový růstový faktor metabolismus   MeSH
• dospělé kmenové buňky cytologie   metabolismus   MeSH
• fibroblastový růstový faktor 2 metabolismus   MeSH
• insulinu podobný růstový faktor I metabolismus   MeSH
• krysa rodu Rattus MeSH
• mícha cytologie   metabolismus   MeSH
• oligodendroglie cytologie   metabolismus   MeSH
• potkani Sprague-Dawley MeSH
• proteoglykany metabolismus   MeSH
• separace buněk * MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antigeny MeSH
• chondroitin sulfate proteoglycan 4 MeSH Prohlížeč
• destičkový růstový faktor MeSH
• fibroblastový růstový faktor 2 MeSH
• insulin-like growth factor-1, rat MeSH Prohlížeč
• insulinu podobný růstový faktor I MeSH
• platelet-derived growth factor A MeSH Prohlížeč
• proteoglykany MeSH

BACKGROUND: Accumulating evidence suggests that breast cancer involves tumour-initiating cells (TICs), which play a role in initiation, metastasis, therapeutic resistance and relapse of the disease. Emerging drugs that target TICs are becoming a focus of contemporary research. Mitocans, a group of compounds that induce apoptosis of cancer cells by destabilising their mitochondria, are showing their potential in killing TICs. In this project, we investigated mitochondrially targeted vitamin E succinate (MitoVES), a recently developed mitocan, for its in vitro and in vivo efficacy against TICs. METHODS: The mammosphere model of breast TICs was established by culturing murine NeuTL and human MCF7 cells as spheres. This model was verified by stem cell marker expression, tumour initiation capacity and chemotherapeutic resistance. Cell susceptibility to MitoVES was assessed and the cell death pathway investigated. In vivo efficacy was studied by grafting NeuTL TICs to form syngeneic tumours. RESULTS: Mammospheres derived from NeuTL and MCF7 breast cancer cells were enriched in the level of stemness, and the sphere cells featured altered mitochondrial function. Sphere cultures were resistant to several established anti-cancer agents while they were susceptible to MitoVES. Killing of mammospheres was suppressed when the mitochondrial complex II, the molecular target of MitoVES, was knocked down. Importantly, MitoVES inhibited progression of syngeneic HER2(high) tumours derived from breast TICs by inducing apoptosis in tumour cells. CONCLUSIONS: These results demonstrate that using mammospheres, a plausible model for studying TICs, drugs that target mitochondria efficiently kill breast tumour-initiating cells.

• MeSH
• apoptóza účinky léků   MeSH
• buněčné sféroidy MeSH
• chemorezistence MeSH
• lidé MeSH
• MFC-7 buňky MeSH
• mitochondrie účinky léků   metabolismus   MeSH
• modely nemocí na zvířatech MeSH
• myši transgenní MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• nádorové buňky kultivované MeSH
• nádorové kmenové buňky účinky léků   metabolismus   MeSH
• nádory prsu farmakoterapie   metabolismus   patologie   MeSH
• protinádorové látky farmakologie   MeSH
• respirační komplex II metabolismus   MeSH
• tokoferoly farmakologie   MeSH
• tumor burden účinky léků   MeSH
• viabilita buněk účinky léků   MeSH
• xenogenní modely - testy protinádorové aktivity MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• protinádorové látky MeSH
• respirační komplex II MeSH
• tokoferoly MeSH