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Schematic of neural crest-derived ocular tissues and their response to injury. (A) Sagittal cross-section of an eye. (B) A higher magnification image showing the neural crest-derived retinal tissues. (C) Retinal injury (indicated by the yellow lightning bolt) is simulated by explantation. (D) GFP-positive retinal cells co-localize with BrdU immunofluorescence in retinal explants from Wnt1Cre:R26RGFP/+ mice.
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Whether it is due to a particular epigenetic signature, or some other component of an embryonic differentiation program, accumulating evidence indicates that the origins of a stem cell has a profound impact on the potential of a tissue to regenerate and repair. Here, we focus on Müller glia, long considered the stem cells of the retina, and their s...
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... and at day 3 after injury (compare Fig. 3C with D). Instead of a loss of cells, cell density is maintained through proliferation (as shown by BrdU immunostaining; Fig. 3E) in the neural crest-derived cells (Fig. 3F). Co-localization of the two signals unambigu- ously demonstrates that the proliferating cells were derived from the neural crest (Fig. 4G). Thus, neural crest- derived cells show a robust ability to proliferate in response to injury, and their survival is dependent upon a WNT ...
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... gen- erate retinal injuries and in these assays, neural crest- derived cells in the retina proliferated after WNT3A treat- ment (Fig. 3). Our data suggest the possibility that the plas- ticity of M€ uller glia, which contributes to the regeneration of the damaged retina, may be attributed to their neural crest origins (See our proposed model in Fig. ...
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Small and cell-type restricted promoters are important tools for basic and preclinical research, and clinical delivery of gene therapies. In clinical gene therapy, ophthalmic trials have been leading the field, with over 50% of ocular clinical trials using promoters that restrict expression based on cell type. Here, 19 human DNA MiniPromoters were...
Citations
... Studies have shown that retinal macroglia are the basis for maintaining retinal neuronal homeostasis [19]. Müller cells, which have the highest content-up to 90%-are the main structural and nutritional support for retinal cells [20]. Astrocytes, on the other hand, play a role in protecting the retina from damage, mainly through the reactive glial proliferation pathway [21]. ...
According to reports, supplementation with appropriate doses of taurine may help to reduce visual fatigue. Presently, some progress has been made in research related to taurine in eye health, but the lack of systematic summaries has led to the neglect of its application in the relief of visual fatigue. This paper, therefore, provides a systematic review of the sources of taurine, including the endogenous metabolic and exogenous dietary pathways, as well as a detailed review of the distribution and production of exogenous taurine. The physiological mechanisms underlying the production of visual fatigue are summarized and the research progress of taurine in relieving visual fatigue is reviewed, including the safety of consumption and the mechanism of action in relieving visual fatigue, in order to provide some reference basis and inspiration for the development and application of taurine in functional foods for relieving visual fatigue.
... All mentioned sequelae dramatically decrease the quality of life of the patients, influencing their social activity and lead in some cases to partial or total professional disability. [1][2][3] In most cases, orbital trauma results from the direct or indirect injuries of orbital bony structures, as well as orbital soft tissue content. Orbital wall fractures lead to appearance of the bony defects requiring reconstruction. ...
... The developed model of orbital trauma of the orbital allows reproducing destructive changes in its content and deep degeneration of the optic nerve, which is consistent with the literature. 11,1,7 According to the literature there are several major factors that complicate the regeneration of the optic nerve. On the one hand, trauma induces apoptosis of retinal ganglion neurons and there is a genetically determined weak ability of injured axons of mature retinal ganglion cells of the retina to regenerate. ...
Orbital trauma is a challenging problem due to such severe sequel as diplopia, decrease of vision or eye motility disorder. However, the conditions of orbital soft tissue content still become underestimated. The aim of this study was to
investigate structural changes in the rat optic nerve after experimental injury followed by treatment with stem cells.
Materials and methods. An experimental model of injury to the orbital soft tissue content in the rat was developed. Forty Wistar rats maintained under daylight were divided into two equal experimental groups. Unlike the rats of Group I, in rats of Group II, the site of injury to the orbital soft tissue mass received postnatal multipotent stem cells, epidermal neural crest stem cells (NCSCs) derived from the bulge of hair follicles.
Results. Comparing the number of glial cells per certain area of the slice (NC) between group І and site without injury (control) after 3 week of observation, it was higher in group I more than 258,8% (p<0,0001) and on 272,4% in group II (p<0,0001). After 6 weeks NC in group I was higher than at previous terms: more then 128,9% (р<0,0001). At the same, NC in group II was higher comparing with previous terms only on 17,1% (р=0,0212). Between the animals of group I at terms of 12 and 24 weeks NC high and wasn’t significantly differ between this terms of observation (ANOVA p=0,4379). In contrast, NC in group II stopped rising between 6 and 12 weeks demonstrating statistical equality (p=0,4563).
Conclusions. It can be assumed that the application of mesenchymal stem cells, derivates of the neural crest, after the experimental orbital trauma, stimulates a recovery of the optic nerve. Further studies should be performed to more deeply discover the neural crest derived stem cell populations, involved into recovery of damaged optic nerves.
... GENERAL DESCRIPTION Müller cells are a heterogeneous population [1,2] originating from the neural crest [3]. 90% of the retina glia consists of MCs that vertically pass through the entire retina from the inner border membrane bordering the vitreous body to the subretinal space. ...
... Neurocristopathy disorders include Hirschsprung's disease, CHARGE syndrome, and Treacher-Collins syndrome, among others. Eye related complications such as ocular coloboma and heterochromia iridis are often known to arise from such diseases [34]. Furthermore, these complications include not only the above congenital diseases but also degenerative diseases of neural crest-derived tissues such as keratoconus, Fuchs dystrophy, and adult-onset primary open-angle glaucoma [1]. ...
Collecting sufficient quantities of primary neural crest cells (NCCs) for experiments is difficult, as NCCs are embryonic transient tissue that basically does not proliferate. We successfully induced NCCs from human induced pluripotent stem cells (iPSCs) in accordance with a previously described method with some modifications. The protocol used in this study efficiently produced large amounts of iPSC-derived NCCs (iPSC-NCCs). Many researchers have recently produced large amounts of iPSC-NCCs and used these to examine the physiological properties, such as migratory activity, and the potential for medical uses such as wound healing. Immunological properties of neural crest cells have yet to be reported. Therefore, the purpose of this study was to assess the immunological properties of human iPSC-NCCs. Our current study showed that iPSC-NCCs were hypoimmunogenic and had immunosuppressive properties in vitro. Expression of HLA class I molecules on iPSC-NCCs was lower than that observed for iPSCs, and there was no expression of HLA class II and co-stimulatory molecules on the cells. With regard to the immunosuppressive properties, iPSC-NCCs greatly inhibited T-cell activation (cell proliferation, production of inflammatory cytokines) after stimulation. iPSC-NCCs constitutively expressed membrane-bound TGF-β, and TGF-β produced by iPSC-NCCs played a critical role in T cell suppression. Thus, cultured human NCCs can fully suppress T-cell activation in vitro. This study may contribute to the realization of using stem cell-derived NCCs in cell-based medicine.
... The use of stem cells for this purpose has been found promising [12]. Due to their unique capabilities, they have the potential for achieving the required effect [13,14]. They are capable, in particular, of differentiating into functionally active cells of the body, and can produce biologically active substances including various growth factors [13,[15][16]. ...
... Due to their unique capabilities, they have the potential for achieving the required effect [13,14]. They are capable, in particular, of differentiating into functionally active cells of the body, and can produce biologically active substances including various growth factors [13,[15][16]. ...
Background: Ocular trauma and its sequelae substantially affect quality of life. Effective methods to promote regeneration of damaged optic nerve (ON) are still to be developed. Purpose: To investigate structural changes in the rat ON after experimental ON injury followed by treatment with stem cells. Materials and Methods: After being subjected to experimental injury, 40 rats were divided into two equal groups depending on whether they did (Group II) or did not receive (Group I) stem cells derived from the bulge of hair follicles of syngeneic animals. Histological and neurohistological techniques were used to investigate structural changes in the traumatized rat ON. Results: Experimental injury to the ON resulted in its degeneration. Stem cell grafting at the site of injury initiated improved ON regeneration, which was evidenced by (1) newly formed nerve fibers and glial columns mostly of oligodendrocytes, (2) reduced glial scar volume due to reduction in the number of astrocytes, and (3) rapid elimination of myelin debris. Conclusion: Injection of neural crest stem cells derived from the bulge of hair follicles of syngeneic animals improves the optic nerve restoration after injury.
... Hence, autologous HFBSCs are potentially suitable for therapeutic application in a broad range of neurological disorders such as ALS, Alzheimer's disease and stroke. They also may be used in cell-based therapies for sensory neurological diseases such as those for ocular or inner ear regeneration (Liu et al. 2014;Huisman and Rivolta 2012). If HFBSCs could be harvested from plucked hairs, their practical utilization for autologous stem cell therapy would increase immensely. ...
Stem cells from the adult hair follicle bulge can differentiate into neurons and glia, which is advantageous for the development of an autologous cell-based therapy for neurological diseases. Consequently, bulge stem cells from plucked hair may increase opportunities for personalized neuroregenerative therapy. Hairs were plucked from the scalps of healthy donors, and the bulges were cultured without prior tissue treatment. Shortly after outgrowth from the bulge, cellular protein expression was established immunohistochemically. The doubling time was calculated upon expansion, and the viability of expanded, cryopreserved cells was assessed after shear stress. The neuroglial differentiation potential was assessed from cryopreserved cells. Shortly after outgrowth, the cells were immunopositive for nestin, SLUG, AP-2α and SOX9, and negative for SOX10. Each bulge yielded approximately 1 × 10(4) cells after three passages. Doubling time was 3.3 (±1.5) days. Cellular viability did not differ significantly from control cells after shear stress. The cells expressed class III β-tubulin (TUBB3) and synapsin-1 after 3 weeks of neuronal differentiation. Glial differentiation yielded KROX20- and MPZ-immunopositive cells after 2 weeks. We demonstrated that human hair follicle bulge-derived stem cells can be cultivated easily, expanded efficiently and kept frozen until needed. After cryopreservation, the cells were viable and displayed both neuronal and glial differentiation potential.
... While this field's scientific knowledge base has accumulated since 1968, it still deals with an unfavourable amount of unknowns that prohibit safe clinical studies. In order to avoid therapy failure and undesirable side effects, the MSC properties under various external environmental conditions have to be perfectly understood (Liu et al., 2014). At present, we recognize that the cultured MSC properties are influenced by two major factors: 1) the inter-individual characteristics of the donor (Katsara, 2011), and 2) the culture medium composition (Suchánek et al., 2013). ...
Foetal calf serum (FCS) is a standard supplement used in media for in vitro stem cell cultivation. This xenogeneic supplement remains widely used for its favourable growth-promoting properties and ease of accessibility; however, it is inherently not fit for human medicine due to its capacity to temper with the cultured cell quality. For this reason, the international community encourages research and development of allogeneic sera, which would expunge this issue. This study aims to investigate the differences in proliferative capacity, phenotype, and differentiation capacity of ecto-mesenchymal stem cells from human exfoliated deciduous teeth (SHED) cultured in vitro in media supplemented with allogeneic and xenogeneic sera. To address these aims, we cultured three lineages of stem cells in media supplemented with FCS in a concentration of 2% + growth factors; human blood plasma and platelet-rich plasma in concentrations of 2% + growth factors, and 10%. Here, the xenogeneic cultivation was considered as a basis for comparison because this serum is commonly used in studies concerning ecto-mesenchymal stem cells. The study shows that multipotent ecto-mesenchymal SHED can be feasibly cultivated in media where the xenogeneic FCS is substituted by allogeneic platelet-rich plasma, considering the cultured cell proliferative and differentiation capacities. We have also proved that different sera impact the cultured cells' phenotype differently, which has major implications for previous and future stem cell research and regenerative therapy.
... M€ uller cells are the only type of retinal glia that share a common embryonic origin with retinal neurons (Turner and Cepko, 1987;Holt et al., 1988;Wetts and Fraser, 1988). Of note, a recent lineage study in the mouse suggests that a subset of M€ uller cells may be derived from the neural crest (Liu et al., 2014). This is quite unexpected and thus clearly deserves further investigation and comparative studies in different vertebrate species. ...
... As mentioned above, a recent study suggested that a subset of M€ uller cells in the mouse retina may derive from the neural crest (Liu et al., 2014). This is quite surprising and contrasts with results of most neural crest lineage tracing studies and with previous evidence that M€ uller glia is exclusively derived from the retinal neuroepithelium. ...
Retinal dystrophies are a major cause of blindness for which there are currently no curative treatments. Transplantation of stem cell-derived neuronal progenitors to replace lost cells has been widely investigated as a therapeutic option. Another promising strategy would be to trigger self-repair mechanisms in patients, through the recruitment of endogenous cells with stemness properties. Accumulating evidence in the last 15 years has revealed that several retinal cell types possess neurogenic potential, thus opening new avenues for regenerative medicine. Among them, Müller glial cells have been shown to be able to undergo a reprogramming process to re-acquire a stem/progenitor state, allowing them to proliferate and generate new neurons for repair following retinal damages. Although Müller cell-dependent spontaneous regeneration is remarkable in some species such as the fish, it is extremely limited and ineffective in mammals. Understanding the cellular events and molecular mechanisms underlying Müller cell activities in species endowed with regenerative capacities could provide knowledge to unlock the restricted potential of their mammalian counterparts. In this context, the present review provides an overview of Müller cell responses to injury across vertebrate model systems and summarizes recent advances in this rapidly evolving field. This article is protected by copyright. All rights reserved.
... Although Müller cells share a lineage with retinal neurons, their time of birth appears to be different. Recent studies found the surprising origin of Müller cells in the neuronal crest cells (Liu et al., 2014a). Birth dating of retinal neurons and Müller cells was determined by 3 H-thymidine-labelling (Sidman, 1961) and ...
OBJECTIVE Retinal ganglion cells (RGCs) are the first affected cells in neuropathies like glaucoma, for that reason it is very important to explore new methods to neuroprotect these neurons. Müller cells are glial cells that provide the neurons with trophic factors and scaffold. The purpose of this study was to analyze the effect of Müller cells on survival and neurite formation in RGCs. METHOD Rat Müller cells were grown until a confluent culture on which rat RGCs were added, using pure culture of rat RGCs as controls. RGCs were labeled with βIII-tubulin, and Müller cells with glutamine synthetase antibodies. In addition, nuclei were stained with DAPI. The number of RGCs and number and neurite length were measured. RESULTS No differences were found in the number of RGCs between control and cells grown on the substrate of Müller cells. The proportion of RGCs with neurites increased when they grew on Müller (RGCs with 1-3 neurites increased from 19% to 43%. The length of neurites also increased in RGCs grown on Müller cells, with the number of RGCs with neurites from 50 to 200 μm increasing from 21% to 41%, and with neurites of more than 200 μm the increase was from 6% to 20%. CONCLUSIONS Müller cells support the survival of RGCs and induced an increase in the number and length of neurites of RGCs.
... Although Müller cells share a lineage with retinal neurons, their time of birth appears to be different. Recent studies found the surprising origin of Müller cells in the neuronal crest cells (Liu et al., 2014a). Birth dating of retinal neurons and Müller cells was determined by 3 H-thymidinelabelling (Sidman, 1961) and all retinal cell types are generated in an orderly fashion, the sequence of which is largely conserved among vertebrates (Vecino and Acera, 2015). ...
The mammalian retina provides an excellent opportunity to study glia-neuron interactions and the interactions of glia with blood vessels. Three main types of glial cells are found in the mammalian retina that serve to maintain retinal homeostasis: astrocytes, Müller cells and resident microglia. Müller cells and astrocytes and microglia not only provide structural support but they are also involved in metabolism, the phagocytosis of neuronal debris, the release of certain transmitters and trophic factors and K(+) uptake. Astrocytes are mostly located in the nerve fibre layer and they accompany the blood vessels in the inner nuclear layer. Indeed, like Müller cells, astrocytic processes cover the blood vessels forming the retinal blood barrier and they fulfil a significant role in ion homeostasis. Among other activities, microglia can be stimulated to fulfil a macrophage function, as well as to interact with other glial cells and neurons by secreting growth factors. This review summarizes the main functional relationships between retinal glial cells and neurons, presenting a general picture of the retina recently modified based on experimental observations. The preferential involvement of the distinct glia cells in terms of the activity in the retina is discussed, for example, while Müller cells may serve as progenitors of retinal neurons, astrocytes and microglia are responsible for synaptic pruning. Since different types of glia participate together in certain activities in the retina, it is imperative to explore the order of redundancy and to explore the heterogeneity among these cells. Recent studies revealed the association of glia cell heterogeneity with specific functions. Finally, the neuroprotective effects of glia on photoreceptors and ganglion cells under normal and adverse conditions will also be explored.
Copyright © 2015. Published by Elsevier Ltd.
