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  1. Article ; Online: The activation of dormant ependymal cells following spinal cord injury.

    Rodriguez-Jimenez, Francisco Javier / Jendelova, Pavla / Erceg, Slaven

    Stem cell research & therapy

    2023  Volume 14, Issue 1, Page(s) 175

    Abstract: 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 ... ...

    Abstract 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.
    MeSH term(s) Humans ; Spinal Cord Injuries/therapy ; Spinal Cord Injuries/metabolism ; Spinal Cord ; Neuroglia/metabolism ; Ependyma/metabolism ; Ion Channels/metabolism
    Chemical Substances Ion Channels
    Language English
    Publishing date 2023-07-05
    Publishing country England
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 2548671-8
    ISSN 1757-6512 ; 1757-6512
    ISSN (online) 1757-6512
    ISSN 1757-6512
    DOI 10.1186/s13287-023-03395-4
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  2. Article ; Online: The activation of dormant ependymal cells following spinal cord injury

    Francisco Javier Rodriguez-Jimenez / Pavla Jendelova / Slaven Erceg

    Stem Cell Research & Therapy, Vol 14, Iss 1, Pp 1-

    2023  Volume 11

    Abstract: Abstract 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 ... ...

    Abstract Abstract 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.
    Keywords Spinal cord injury ; Ependymal cells ; Activation ; Regeneration ; Medicine (General) ; R5-920 ; Biochemistry ; QD415-436
    Subject code 571 ; 572
    Language English
    Publishing date 2023-07-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Alzheimer's disease and synapse Loss: What can we learn from induced pluripotent stem Cells?

    Rodriguez-Jimenez, Francisco Javier / Ureña-Peralta, Juan / Jendelova, Pavla / Erceg, Slaven

    Journal of advanced research

    2023  Volume 54, Page(s) 105–118

    Abstract: Background: Synaptic dysfunction is a major contributor to Alzheimeŕs disease (AD) pathogenesis in addition to the formation of neuritic β-amyloid plaques and neurofibrillary tangles of hyperphosphorylated Tau protein. However, how these features ... ...

    Abstract Background: Synaptic dysfunction is a major contributor to Alzheimeŕs disease (AD) pathogenesis in addition to the formation of neuritic β-amyloid plaques and neurofibrillary tangles of hyperphosphorylated Tau protein. However, how these features contribute to synaptic dysfunction and axonal loss remains unclear. While years of considerable effort have been devoted to gaining an improved understanding of this devastating disease, the unavailability of patient-derived tissues, considerable genetic heterogeneity, and lack of animal models that faithfully recapitulate human AD have hampered the development of effective treatment options. Ongoing progress in human induced pluripotent stem cell (hiPSC) technology has permitted the derivation of patient- and disease-specific stem cells with unlimited self-renewal capacity. These cells can differentiate into AD-affected cell types, which support studies of disease mechanisms, drug discovery, and the development of cell replacement therapies in traditional and advanced cell culture models.
    Aim of review: To summarize current hiPSC-based AD models, highlighting the associated achievements and challenges with a primary focus on neuron and synapse loss.
    Key scientific concepts of review: We aim to identify how hiPSC models can contribute to understanding AD-associated synaptic dysfunction and axonal loss. hiPSC-derived neural cells, astrocytes, and microglia, as well as more sophisticated cellular organoids, may represent reliable models to investigate AD and identify early markers of AD-associated neural degeneration.
    MeSH term(s) Animals ; Humans ; Alzheimer Disease/genetics ; Alzheimer Disease/metabolism ; Alzheimer Disease/pathology ; Induced Pluripotent Stem Cells/metabolism ; Induced Pluripotent Stem Cells/pathology ; Amyloid beta-Peptides/genetics ; Amyloid beta-Peptides/metabolism ; Neurons/metabolism ; Synapses/metabolism
    Chemical Substances Amyloid beta-Peptides
    Language English
    Publishing date 2023-01-14
    Publishing country Egypt
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 2541849-X
    ISSN 2090-1224 ; 2090-1224
    ISSN (online) 2090-1224
    ISSN 2090-1224
    DOI 10.1016/j.jare.2023.01.006
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  4. Article: Stem Cell-Based Therapy in Transplantation and Immune-Mediated Diseases.

    Volarevic, Vladislav / Lako, Majlinda / Erceg, Slaven / Stojkovic, Miodrag

    Stem cells international

    2017  Volume 2017, Page(s) 7379136

    Language English
    Publishing date 2017-09-06
    Publishing country United States
    Document type Editorial
    ZDB-ID 2573856-2
    ISSN 1687-9678 ; 1687-966X
    ISSN (online) 1687-9678
    ISSN 1687-966X
    DOI 10.1155/2017/7379136
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  5. Article ; Online: Stem Cell-Based Therapy in Transplantation and Immune-Mediated Diseases

    Vladislav Volarevic / Majlinda Lako / Slaven Erceg / Miodrag Stojkovic

    Stem Cells International, Vol

    2017  Volume 2017

    Keywords Internal medicine ; RC31-1245
    Language English
    Publishing date 2017-01-01T00:00:00Z
    Publisher Hindawi Limited
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article: Neural Stem Cells Derived from Human-Induced Pluripotent Stem Cells and Their Use in Models of CNS Injury.

    Jendelova, Pavla / Sykova, Eva / Erceg, Slaven

    Results and problems in cell differentiation

    2018  Volume 66, Page(s) 89–102

    Abstract: 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 ... ...

    Abstract 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.
    MeSH term(s) Cell Differentiation ; Cellular Reprogramming ; Humans ; Induced Pluripotent Stem Cells/cytology ; Models, Neurological ; Neural Stem Cells/cytology ; Spinal Cord Injuries/pathology ; Spinal Cord Injuries/therapy ; Stroke/pathology ; Stroke/therapy ; Transcription Factors/metabolism
    Chemical Substances Transcription Factors
    Language English
    Publishing date 2018-09-12
    Publishing country Germany
    Document type Journal Article
    ISSN 0080-1844
    ISSN 0080-1844
    DOI 10.1007/978-3-319-93485-3_3
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  7. Article: Retinal Pigment Epithelium Cell Development: Extrapolating Basic Biology to Stem Cell Research.

    Gupta, Santosh / Lytvynchuk, Lyubomyr / Ardan, Taras / Studenovska, Hana / Faura, Georgina / Eide, Lars / Znaor, Ljubo / Erceg, Slaven / Stieger, Knut / Motlik, Jan / Bharti, Kapil / Petrovski, Goran

    Biomedicines

    2023  Volume 11, Issue 2

    Abstract: The retinal pigment epithelium (RPE) forms an important cellular monolayer, which contributes to the normal physiology of the eye. Damage to the RPE leads to the development of degenerative diseases, such as age-related macular degeneration (AMD). Apart ... ...

    Abstract The retinal pigment epithelium (RPE) forms an important cellular monolayer, which contributes to the normal physiology of the eye. Damage to the RPE leads to the development of degenerative diseases, such as age-related macular degeneration (AMD). Apart from acting as a physical barrier between the retina and choroidal blood vessels, the RPE is crucial in maintaining photoreceptor (PR) and visual functions. Current clinical intervention to treat early stages of AMD includes stem cell-derived RPE transplantation, which is still in its early stages of evolution. Therefore, it becomes essential to derive RPEs which are functional and exhibit features as observed in native human RPE cells. The conventional strategy is to use the knowledge obtained from developmental studies using various animal models and stem cell-based exploratory studies to understand RPE biogenies and developmental trajectory. This article emphasises such studies and aims to present a comprehensive understanding of the basic biology, including the genetics and molecular pathways of RPE development. It encompasses basic developmental biology and stem cell-based developmental studies to uncover RPE differentiation. Knowledge of the in utero developmental cues provides an inclusive methodology required for deriving RPEs using stem cells.
    Language English
    Publishing date 2023-01-23
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2720867-9
    ISSN 2227-9059
    ISSN 2227-9059
    DOI 10.3390/biomedicines11020310
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  8. Article ; Online: Progress in Stem Cells-Based Replacement Therapy for Retinal Pigment Epithelium: In Vitro Differentiation to In Vivo Delivery.

    Gupta, Santosh / Lytvynchuk, Lyubomyr / Ardan, Taras / Studenovska, Hana / Sharma, Ruchi / Faura, Georgina / Eide, Lars / Shanker Verma, Rama / Znaor, Ljubo / Erceg, Slaven / Stieger, Knut / Motlik, Jan / Petrovski, Goran / Bharti, Kapil

    Stem cells translational medicine

    2023  Volume 12, Issue 8, Page(s) 536–552

    Abstract: Retinal pigment epithelium (RPE) is a critical cell monolayer forming the blood-retina-barrier (BRB) and a permeable bridge between the choriocapillaris and the retina. RPE is also crucial in maintaining photoreceptor function and for completing the ... ...

    Abstract Retinal pigment epithelium (RPE) is a critical cell monolayer forming the blood-retina-barrier (BRB) and a permeable bridge between the choriocapillaris and the retina. RPE is also crucial in maintaining photoreceptor function and for completing the visual cycle. Loss of the RPE is associated with the development of degenerative diseases like age-related macular degeneration (AMD). To treat diseases like AMD, pluripotent stem cell-derived RPE (pRPE) has been recently explored extensively as a regenerative module. pRPE like other ectodermal tissues requires specific lineage differentiation and long-term in vitro culturing for maturation. Therefore, understanding the differentiation process of RPE could be useful for stem cell-based RPE derivation. Developing pRPE-based transplants and delivering them into the subretinal space is another aspect that has garnered interest in the last decade. In this review, we discuss the basic strategies currently employed for stem cell-based RPE derivation, their delivery, and recent clinical studies related to pRPE transplantation in patients. We have also discussed a few limitations with in vitro RPE culture and potential solutions to overcome such problems which can be helpful in developing functional RPE tissue.
    MeSH term(s) Humans ; Retinal Pigment Epithelium/metabolism ; Retina ; Macular Degeneration/therapy ; Macular Degeneration/metabolism ; Cell Differentiation ; Pluripotent Stem Cells
    Language English
    Publishing date 2023-07-17
    Publishing country England
    Document type Review ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2642270-0
    ISSN 2157-6580 ; 2157-6580
    ISSN (online) 2157-6580
    ISSN 2157-6580
    DOI 10.1093/stcltm/szad039
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  9. Article: Organized Neurogenic-Niche-Like Pinwheel Structures Discovered in Spinal Cord Tissue-Derived Neurospheres.

    Rodriguez-Jimenez, Francisco Javier / Clemente, Eleonora / Moreno-Manzano, Victoria / Erceg, Slaven

    Frontiers in cell and developmental biology

    2019  Volume 7, Page(s) 334

    Abstract: The neurogenic niche of the subventricular zone (SVZ) in adult brain tissue takes the form of a pinwheel-like cytoarchitectural structure, with mono-ciliated astrocytes displaying neural stem cell (NSC) characteristics present in the core surrounded by ... ...

    Abstract The neurogenic niche of the subventricular zone (SVZ) in adult brain tissue takes the form of a pinwheel-like cytoarchitectural structure, with mono-ciliated astrocytes displaying neural stem cell (NSC) characteristics present in the core surrounded by ciliated ependymal cells. For the first time, we have demonstrated the formation of similar pinwheel structures in spinal cord and SVZ tissue-derived neurospheres cultured
    Language English
    Publishing date 2019-12-20
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2737824-X
    ISSN 2296-634X
    ISSN 2296-634X
    DOI 10.3389/fcell.2019.00334
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  10. Article ; Online: Concise Review: Human Induced Pluripotent Stem Cell Models of Retinitis Pigmentosa.

    Artero Castro, Ana / Lukovic, Dunja / Jendelova, Pavla / Erceg, Slaven

    Stem cells (Dayton, Ohio)

    2018  Volume 36, Issue 4, Page(s) 474–481

    Abstract: Hereditary retinal dystrophies, specifically retinitis pigmentosa (RP) are clinically and genetically heterogeneous diseases affecting primarily retinal cells and retinal pigment epithelial cells with blindness as a final outcome. Understanding the ... ...

    Abstract Hereditary retinal dystrophies, specifically retinitis pigmentosa (RP) are clinically and genetically heterogeneous diseases affecting primarily retinal cells and retinal pigment epithelial cells with blindness as a final outcome. Understanding the pathogenicity behind these diseases has been largely precluded by the unavailability of affected tissue from patients, large genetic heterogeneity and animal models that do not faithfully represent some human diseases. A landmark discovery of human induced pluripotent stem cells (hiPSCs) permitted the derivation of patient-specific cells. These cells have unlimited self-renewing capacity and the ability to differentiate into RP-affected cell types, allowing the studies of disease mechanism, drug discovery, and cell replacement therapies, both as individual cell types and organoid cultures. Together with precise genome editing, the patient specific hiPSC technology offers novel strategies for targeting the pathogenic mutations and design therapies toward retinal dystrophies. This study summarizes current hiPSC-based RP models and highlights key achievements and challenges of these cellular models, as well as questions that still remain unanswered. Stem Cells 2018;36:474-481.
    MeSH term(s) Animals ; Autografts ; Cell Differentiation ; Disease Models, Animal ; Gene Editing ; Genome, Human ; Humans ; Induced Pluripotent Stem Cells/metabolism ; Induced Pluripotent Stem Cells/pathology ; Retinitis Pigmentosa/genetics ; Retinitis Pigmentosa/metabolism ; Retinitis Pigmentosa/pathology ; Retinitis Pigmentosa/therapy ; Stem Cell Transplantation
    Language English
    Publishing date 2018-02-07
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1143556-2
    ISSN 1549-4918 ; 1066-5099
    ISSN (online) 1549-4918
    ISSN 1066-5099
    DOI 10.1002/stem.2783
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