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Sample records for neural crest-derived mesenchyme

  1. Neural crest-derived mesenchymal cells require Wnt signaling for their development and drive invagination of the telencephalic midline.

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    Youngshik Choe

    Full Text Available Embryonic neural crest cells contribute to the development of the craniofacial mesenchyme, forebrain meninges and perivascular cells. In this study, we investigated the function of ß-catenin signaling in neural crest cells abutting the dorsal forebrain during development. In the absence of ß-catenin signaling, neural crest cells failed to expand in the interhemispheric region and produced ectopic smooth muscle cells instead of generating dermal and calvarial mesenchyme. In contrast, constitutive expression of stabilized ß-catenin in neural crest cells increased the number of mesenchymal lineage precursors suggesting that ß-catenin signaling is necessary for the expansion of neural crest-derived mesenchymal cells. Interestingly, the loss of neural crest-derived mesenchymal stem cells (MSCs leads to failure of telencephalic midline invagination and causes ventricular system defects. This study shows that ß-catenin signaling is required for the switch of neural crest cells to MSCs and mediates the expansion of MSCs to drive the formation of mesenchymal structures of the head. Furthermore, loss of these structures causes striking defects in forebrain morphogenesis.

  2. Constitutively active Notch1 converts cranial neural crest-derived frontonasal mesenchyme to perivascular cells in vivo

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    Sophie R. Miller

    2017-03-01

    Full Text Available Perivascular/mural cells originate from either the mesoderm or the cranial neural crest. Regardless of their origin, Notch signalling is necessary for their formation. Furthermore, in both chicken and mouse, constitutive Notch1 activation (via expression of the Notch1 intracellular domain is sufficient in vivo to convert trunk mesoderm-derived somite cells to perivascular cells, at the expense of skeletal muscle. In experiments originally designed to investigate the effect of premature Notch1 activation on the development of neural crest-derived olfactory ensheathing glial cells (OECs, we used in ovo electroporation to insert a tetracycline-inducible NotchΔE construct (encoding a constitutively active mutant of mouse Notch1 into the genome of chicken cranial neural crest cell precursors, and activated NotchΔE expression by doxycycline injection at embryonic day 4. NotchΔE-targeted cells formed perivascular cells within the frontonasal mesenchyme, and expressed a perivascular marker on the olfactory nerve. Hence, constitutively activating Notch1 is sufficient in vivo to drive not only somite cells, but also neural crest-derived frontonasal mesenchyme and perhaps developing OECs, to a perivascular cell fate. These results also highlight the plasticity of neural crest-derived mesenchyme and glia.

  3. Regeneration of neural crest derivatives in the Xenopus tadpole tail

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    Slack Jonathan MW

    2007-05-01

    Full Text Available Abstract Background After amputation of the Xenopus tadpole tail, a functionally competent new tail is regenerated. It contains spinal cord, notochord and muscle, each of which has previously been shown to derive from the corresponding tissue in the stump. The regeneration of the neural crest derivatives has not previously been examined and is described in this paper. Results Labelling of the spinal cord by electroporation, or by orthotopic grafting of transgenic tissue expressing GFP, shows that no cells emigrate from the spinal cord in the course of regeneration. There is very limited regeneration of the spinal ganglia, but new neurons as well as fibre tracts do appear in the regenerated spinal cord and the regenerated tail also contains abundant peripheral innervation. The regenerated tail contains a normal density of melanophores. Cell labelling experiments show that melanophores do not arise from the spinal cord during regeneration, nor from the mesenchymal tissues of the skin, but they do arise by activation and proliferation of pre-existing melanophore precursors. If tails are prepared lacking melanophores, then the regenerates also lack them. Conclusion On regeneration there is no induction of a new neural crest similar to that seen in embryonic development. However there is some regeneration of neural crest derivatives. Abundant melanophores are regenerated from unpigmented precursors, and, although spinal ganglia are not regenerated, sufficient sensory systems are produced to enable essential functions to continue.

  4. Isolation and characterization of neural crest-derived stem cells from dental pulp of neonatal mice.

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    Kajohnkiart Janebodin

    Full Text Available Dental pulp stem cells (DPSCs are shown to reside within the tooth and play an important role in dentin regeneration. DPSCs were first isolated and characterized from human teeth and most studies have focused on using this adult stem cell for clinical applications. However, mouse DPSCs have not been well characterized and their origin(s have not yet been elucidated. Herein we examined if murine DPSCs are neural crest derived and determined their in vitro and in vivo capacity. DPSCs from neonatal murine tooth pulp expressed embryonic stem cell and neural crest related genes, but lacked expression of mesodermal genes. Cells isolated from the Wnt1-Cre/R26R-LacZ model, a reporter of neural crest-derived tissues, indicated that DPSCs were Wnt1-marked and therefore of neural crest origin. Clonal DPSCs showed multi-differentiation in neural crest lineage for odontoblasts, chondrocytes, adipocytes, neurons, and smooth muscles. Following in vivo subcutaneous transplantation with hydroxyapatite/tricalcium phosphate, based on tissue/cell morphology and specific antibody staining, the clones differentiated into odontoblast-like cells and produced dentin-like structure. Conversely, bone marrow stromal cells (BMSCs gave rise to osteoblast-like cells and generated bone-like structure. Interestingly, the capillary distribution in the DPSC transplants showed close proximity to odontoblasts whereas in the BMSC transplants bone condensations were distant to capillaries resembling dentinogenesis in the former vs. osteogenesis in the latter. Thus we demonstrate the existence of neural crest-derived DPSCs with differentiation capacity into cranial mesenchymal tissues and other neural crest-derived tissues. In turn, DPSCs hold promise as a source for regenerating cranial mesenchyme and other neural crest derived tissues.

  5. Isolation and Characterization of Neural Crest-Derived Stem Cells from Dental Pulp of Neonatal Mice

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    Janebodin, Kajohnkiart; Horst, Orapin V.; Ieronimakis, Nicholas; Balasundaram, Gayathri; Reesukumal, Kanit; Pratumvinit, Busadee; Reyes, Morayma

    2011-01-01

    Dental pulp stem cells (DPSCs) are shown to reside within the tooth and play an important role in dentin regeneration. DPSCs were first isolated and characterized from human teeth and most studies have focused on using this adult stem cell for clinical applications. However, mouse DPSCs have not been well characterized and their origin(s) have not yet been elucidated. Herein we examined if murine DPSCs are neural crest derived and determined their in vitro and in vivo capacity. DPSCs from neonatal murine tooth pulp expressed embryonic stem cell and neural crest related genes, but lacked expression of mesodermal genes. Cells isolated from the Wnt1-Cre/R26R-LacZ model, a reporter of neural crest-derived tissues, indicated that DPSCs were Wnt1-marked and therefore of neural crest origin. Clonal DPSCs showed multi-differentiation in neural crest lineage for odontoblasts, chondrocytes, adipocytes, neurons, and smooth muscles. Following in vivo subcutaneous transplantation with hydroxyapatite/tricalcium phosphate, based on tissue/cell morphology and specific antibody staining, the clones differentiated into odontoblast-like cells and produced dentin-like structure. Conversely, bone marrow stromal cells (BMSCs) gave rise to osteoblast-like cells and generated bone-like structure. Interestingly, the capillary distribution in the DPSC transplants showed close proximity to odontoblasts whereas in the BMSC transplants bone condensations were distant to capillaries resembling dentinogenesis in the former vs. osteogenesis in the latter. Thus we demonstrate the existence of neural crest-derived DPSCs with differentiation capacity into cranial mesenchymal tissues and other neural crest-derived tissues. In turn, DPSCs hold promise as a source for regenerating cranial mesenchyme and other neural crest derived tissues. PMID:22087335

  6. Cranial neural crest-derived mesenchymal proliferation is regulated by Msx1-mediated p19(INK4d) expression during odontogenesis.

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    Han, Jun; Ito, Yoshihiro; Yeo, Jae Yong; Sucov, Henry M; Maas, Richard; Chai, Yang

    2003-09-01

    Neural crest cells are multipotential progenitors that contribute to various cell and tissue types during embryogenesis. Here, we have investigated the molecular and cellular mechanism by which the fate of neural crest cell is regulated during tooth development. Using a two- component genetic system for indelibly marking the progeny of neural crest cells, we provide in vivo evidence of a deficiency of CNC-derived dental mesenchyme in Msx1 null mutant mouse embryos. The deficiency of the CNC results from an elevated CDK inhibitor p19(INK4d) activity and the disruption of cell proliferation. Interestingly, in the absence of Msx1, the CNC-derived dental mesenchyme misdifferentiates and possesses properties consistent with a neuronal fate, possibly through a default mechanism. Attenuation of p19(INK4d) in Msx1 null mutant mandibular explants restores mitotic activity in the dental mesenchyme, demonstrating the functional significance of Msx1-mediated p19(INK4d) expression in regulating CNC cell proliferation during odontogenesis. Collectively, our results demonstrate that homeobox gene Msx1 regulates the fate of CNC cells by controlling the progression of the cell cycle. Genetic mutation of Msx1 may alternatively instruct the fate of these progenitor cells during craniofacial development.

  7. [Phenotypic plasticity of neural crest-derived melanocytes and Schwann cells].

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    Dupin, Elisabeth

    2011-01-01

    expression. This review considers the issue of whether neural crest-derived lineages are endowed with some phenotypic plasticity. Emphasis is put on the ability of pigment cells and Schwann cells to dedifferentiate and reprogram their fate in vitro. To address this question, we have studied the clonal progeny of differentiated Schwann cells and melanocytes after their isolation from the sciatic nerve and the back skin of quail embryos, respectively. When stimulated to proliferate in vitro in the presence of endothelin-3, both cell types were able to dedifferentiate and produce alternative neural crest-derived cell lineages. Individual Schwann cells isolated by FACS, using a glial-specific surface marker, gave rise in culture to pigment cells and myofibroblasts/smooth muscle cells. Treatment of the cultures with endothelin-3 was required for Schwann cell conversion into melanocytes, which involved acquisition of multipotency. Moreover, Schwann cell plasticity could also be induced in vivo: following transplantation into the branchial arch of a young chick host embryo, dedifferentiating Schwann cells were able to integrate the forming head structures of the host and, specifically, to contribute smooth muscle cells to the wall of cranial blood vessels. We also analyzed the in vitro behavior of individual pigment cells obtained by microdissection and enzymatic treatment of quail epidermis at embryonic and hatching stages. In single cell cultures treated with endothelin-3, pigment cells strongly proliferated while rapidly dedifferentiating into unpigmented cells, leading to the formation of large colonies that comprised glial cells and myofibroblasts in addition to melanocytes. By serially subcloning these primary colonies, we could efficiently propagate a bipotent glial-melanocytic precursor that is generated in the progeny of the melanocytic founder. These data therefore suggest that pigment cells have the ability to revert back to the state of self-renewing neural crest

  8. Physiological Plasticity of Neural-Crest-Derived Stem Cells in the Adult Mammalian Carotid Body

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    Valentina Annese

    2017-04-01

    Full Text Available Adult stem cell plasticity, or the ability of somatic stem cells to cross boundaries and differentiate into unrelated cell types, has been a matter of debate in the last decade. Neural-crest-derived stem cells (NCSCs display a remarkable plasticity during development. Whether adult populations of NCSCs retain this plasticity is largely unknown. Herein, we describe that neural-crest-derived adult carotid body stem cells (CBSCs are able to undergo endothelial differentiation in addition to their reported role in neurogenesis, contributing to both neurogenic and angiogenic processes taking place in the organ during acclimatization to hypoxia. Moreover, CBSC conversion into vascular cell types is hypoxia inducible factor (HIF dependent and sensitive to hypoxia-released vascular cytokines such as erythropoietin. Our data highlight a remarkable physiological plasticity in an adult population of tissue-specific stem cells and could have impact on the use of these cells for cell therapy.

  9. Physiological Plasticity of Neural-Crest-Derived Stem Cells in the Adult Mammalian Carotid Body.

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    Annese, Valentina; Navarro-Guerrero, Elena; Rodríguez-Prieto, Ismael; Pardal, Ricardo

    2017-04-18

    Adult stem cell plasticity, or the ability of somatic stem cells to cross boundaries and differentiate into unrelated cell types, has been a matter of debate in the last decade. Neural-crest-derived stem cells (NCSCs) display a remarkable plasticity during development. Whether adult populations of NCSCs retain this plasticity is largely unknown. Herein, we describe that neural-crest-derived adult carotid body stem cells (CBSCs) are able to undergo endothelial differentiation in addition to their reported role in neurogenesis, contributing to both neurogenic and angiogenic processes taking place in the organ during acclimatization to hypoxia. Moreover, CBSC conversion into vascular cell types is hypoxia inducible factor (HIF) dependent and sensitive to hypoxia-released vascular cytokines such as erythropoietin. Our data highlight a remarkable physiological plasticity in an adult population of tissue-specific stem cells and could have impact on the use of these cells for cell therapy. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  10. Epigenetic marks define the lineage and differentiation potential of two distinct neural crest-derived intermediate odontogenic progenitor populations.

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    Gopinathan, Gokul; Kolokythas, Antonia; Luan, Xianghong; Diekwisch, Thomas G H

    2013-06-15

    Epigenetic mechanisms, such as histone modifications, play an active role in the differentiation and lineage commitment of mesenchymal stem cells. In the present study, epigenetic states and differentiation profiles of two odontogenic neural crest-derived intermediate progenitor populations were compared: dental pulp (DP) and dental follicle (DF). ChIP on chip assays revealed substantial H3K27me3-mediated repression of odontoblast lineage genes DSPP and dentin matrix protein 1 (DMP1) in DF cells, but not in DP cells. Mineralization inductive conditions caused steep increases of mineralization and patterning gene expression levels in DP cells when compared to DF cells. In contrast, mineralization induction resulted in a highly dynamic histone modification response in DF cells, while there was only a subdued effect in DP cells. Both DF and DP progenitors featured H3K4me3-active marks on the promoters of early mineralization genes RUNX2, MSX2, and DLX5, while OSX, IBSP, and BGLAP promoters were enriched for H3K9me3 or H3K27me3. Compared to DF cells, DP cells expressed higher levels of three pluripotency-associated genes, OCT4, NANOG, and SOX2. Finally, gene ontology comparison of bivalent marks unique for DP and DF cells highlighted cell-cell attachment genes in DP cells and neurogenesis genes in DF cells. In conclusion, the present study indicates that the DF intermediate odontogenic neural crest lineage is distinguished from its DP counterpart by epigenetic repression of DSPP and DMP1 genes and through dynamic histone enrichment responses to mineralization induction. Findings presented here highlight the crucial role of epigenetic regulatory mechanisms in the terminal differentiation of odontogenic neural crest lineages.

  11. In vitro cementoblast-like differentiation of postmigratory neural crest-derived p75{sup +} stem cells with dental follicle cell conditioned medium

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    Wen, Xiujie; Liu, Luchuan; Deng, Manjing; Liu, Rui; Zhang, Li; Nie, Xin, E-mail: dr.xinnie@gmail.com

    2015-09-10

    Cranial neural crest-derived cells (CNCCs) play important role in epithelial–mesenchymal interactions during tooth morphogenesis. However, the heterogeneity of CNCCs and their tendency to spontaneously differentiate along smooth muscle or osteoblast lineages in vitro limit further understanding of their biological properties. We studied the differentiation properties of isolated rat embryonic postmigratory CNCCs, expressing p75 neurotrophin receptor (p75NTR). These p75NTR positive (p75{sup +}) CNCCs, isolated using fluorescence activated cell sorter, exhibited fibroblast-like morphology and characteristics of mesenchymal stem cells. Incubation of p75{sup +} CNCCs in dental follicle cell conditioned medium (DFCCM) combined with dentin non-collagenous proteins (dNCPs), altered their morphological features to cementoblast-like appearance. These cells also showed low proliferative activity, high ALP activity and significantly increased calcified nodule formation. Markers related to mineralization or specific to cementoblast lineage were highly expressed in dNCPs/DFCCM-treated p75{sup +} cells, suggesting their differentiation along cementoblast-like lineage. p75{sup +} stem cells selected from postmigratory CNCCs represent a pure stem cell population and could be used as a stem cell model for in vitro studies due to their intrinsic ability to differentiate to neuronal cells and transform from neuroectoderm to ectomesenchyme. They can provide a potential stem cell resource for tooth engineering studies and help to further investigate mechanisms of epithelial–mesenchymal interactions in tooth morphogenesis. - Highlights: • Cranial neural crest-derived cells (CNCCs) take part in tooth morphogenesis. • positive (p75{sup +}) CNCCs are fibroblast-like and resemble mesenchymal stem cells. • p75{sup +} CNCCs in dental follicle cell medium (DFCCM/dNCP) appear like cementoblasts. • DFCCM/dNCP-treated p75{sup +} cells express cementoblast specific mineralization

  12. Distinct functional and temporal requirements for zebrafish Hdac1 during neural crest-derived craniofacial and peripheral neuron development.

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    Myron S Ignatius

    Full Text Available The regulation of gene expression is accomplished by both genetic and epigenetic means and is required for the precise control of the development of the neural crest. In hdac1(b382 mutants, craniofacial cartilage development is defective in two distinct ways. First, fewer hoxb3a, dlx2 and dlx3-expressing posterior branchial arch precursors are specified and many of those that are consequently undergo apoptosis. Second, in contrast, normal numbers of progenitors are present in the anterior mandibular and hyoid arches, but chondrocyte precursors fail to terminally differentiate. In the peripheral nervous system, there is a disruption of enteric, DRG and sympathetic neuron differentiation in hdac1(b382 mutants compared to wildtype embryos. Specifically, enteric and DRG-precursors differentiate into neurons in the anterior gut and trunk respectively, while enteric and DRG neurons are rarely present in the posterior gut and tail. Sympathetic neuron precursors are specified in hdac1(b382 mutants and they undergo generic neuronal differentiation but fail to undergo noradrenergic differentiation. Using the HDAC inhibitor TSA, we isolated enzyme activity and temporal requirements for HDAC function that reproduce hdac1(b382 defects in craniofacial and sympathetic neuron development. Our study reveals distinct functional and temporal requirements for zebrafish hdac1 during neural crest-derived craniofacial and peripheral neuron development.

  13. Intrastriatal transplantation of adult human neural crest-derived stem cells improves functional outcome in parkinsonian rats.

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    Müller, Janine; Ossig, Christiana; Greiner, Johannes F W; Hauser, Stefan; Fauser, Mareike; Widera, Darius; Kaltschmidt, Christian; Storch, Alexander; Kaltschmidt, Barbara

    2015-01-01

    Parkinson's disease (PD) is considered the second most frequent and one of the most severe neurodegenerative diseases, with dysfunctions of the motor system and with nonmotor symptoms such as depression and dementia. Compensation for the progressive loss of dopaminergic (DA) neurons during PD using current pharmacological treatment strategies is limited and remains challenging. Pluripotent stem cell-based regenerative medicine may offer a promising therapeutic alternative, although the medical application of human embryonic tissue and pluripotent stem cells is still a matter of ethical and practical debate. Addressing these challenges, the present study investigated the potential of adult human neural crest-derived stem cells derived from the inferior turbinate (ITSCs) transplanted into a parkinsonian rat model. Emphasizing their capability to give rise to nervous tissue, ITSCs isolated from the adult human nose efficiently differentiated into functional mature neurons in vitro. Additional successful dopaminergic differentiation of ITSCs was subsequently followed by their transplantation into a unilaterally lesioned 6-hydroxydopamine rat PD model. Transplantation of predifferentiated or undifferentiated ITSCs led to robust restoration of rotational behavior, accompanied by significant recovery of DA neurons within the substantia nigra. ITSCs were further shown to migrate extensively in loose streams primarily toward the posterior direction as far as to the midbrain region, at which point they were able to differentiate into DA neurons within the locus ceruleus. We demonstrate, for the first time, that adult human ITSCs are capable of functionally recovering a PD rat model. ©AlphaMed Press.

  14. Neural crest-derived dental stem cells--where we are and where we are going.

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    Mayo, Vera; Sawatari, Yoh; Huang, C-Y Charles; Garcia-Godoy, Franklin

    2014-09-01

    There are five types of post-natal human dental stem cells that have been identified, isolated and characterized. Here, we review the information available on dental stem cells as well as their potential applications in dentistry, regenerative medicine and the development of other therapeutic approaches. Data pertinent to dental stem cells and their applications, published in peer-reviewed journals from 1982 to 2013 in English were reviewed. Sources were retrieved from PubMed databases as well as related references that the electronic search yielded. Manuscripts describing the origin, retrieval, characterization and application of dental stem cells were obtained and reviewed. Dental stem cell populations present properties similar to those of mesenchymal stem cells, such as the ability to self-renew and the potential for multilineage differentiation. While they have greater capacity to give rise to odontogenic cells and regenerate dental pulp and periodontal tissue, they have the capacity to differentiate into all three germ line cells, proving that a population of pluripotent stem cells exists in the dental tissues. Dental stem cells have the capacity to differentiate into endoderm, mesoderm and ectoderm tissues. Consequently they do not only have applications in dentistry, but also neurodegenerative and ischemic diseases, diabetes research, bone repair, and other applications in the field of tissue regeneration. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Enrichment and Schwann Cell Differentiation of Neural Crest-derived Dental Pulp Stem Cells.

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    Al-Zer, Heba; Apel, Christian; Heiland, Max; Friedrich, Reinhard E; Jung, Ole; Kroeger, Nadja; Eichhorn, Wolfgang; Smeets, Ralf

    2015-01-01

    As already described in previous studies, neural crest stem cells (NCSCs) can be found in adult human dental pulp. The present study investigated the methodology for enrichment and differentiation-induction of the above mentioned cells. Dental pulp was extracted from human wisdom teeth of four patients and subsequently cultured as explants on fibronectin-coated plates in neurobasal medium supplemented with B27, basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), insulin, l-glutamine and neuregulin-β1. The cells were then characterized by immunofluorescence, while their differentiation-potential was tested by the attempt to induce cells into different lineages, i.e. osteogenic, melanocytic and glial. The enriched cell population expressed nestin, CD271 and SOX10, which are well-known markers for NCSCs. Consequently, the cells were successfully induced to differentiate into osteoblasts, melanocytes and Schwann cells, expressing the corresponding differentiation markers. Human adult dental pulp contains a population of stem cells with neural crest ontogeny, which can thus be recruited for multiple regenerative therapies. Copyright © 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  16. ADAM10 is essential for cranial neural crest-derived maxillofacial bone development

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    Tan, Yu, E-mail: tanyu2048@163.com; Fu, Runqing, E-mail: furunqing@sjtu.edu.cn; Liu, Jiaqiang, E-mail: liujqmj@163.com; Wu, Yong, E-mail: wyonger@gmail.com; Wang, Bo, E-mail: wb228@126.com; Jiang, Ning, E-mail: 179639060@qq.com; Nie, Ping, E-mail: nieping1011@sina.com; Cao, Haifeng, E-mail: 0412chf@163.com; Yang, Zhi, E-mail: wcums1981@163.com; Fang, Bing, E-mail: fangbing@sjtu.edu.cn

    2016-07-08

    Growth disorders of the craniofacial bones may lead to craniofacial deformities. The majority of maxillofacial bones are derived from cranial neural crest cells via intramembranous bone formation. Any interruption of the craniofacial skeleton development process might lead to craniofacial malformation. A disintegrin and metalloprotease (ADAM)10 plays an essential role in organ development and tissue integrity in different organs. However, little is known about its function in craniofacial bone formation. Therefore, we investigated the role of ADAM10 in the developing craniofacial skeleton, particularly during typical mandibular bone development. First, we showed that ADAM10 was expressed in a specific area of the craniofacial bone and that the expression pattern dynamically changed during normal mouse craniofacial development. Then, we crossed wnt1-cre transgenic mice with adam10-flox mice to generate ADAM10 conditional knockout mice. The stereomicroscopic, radiographic, and von Kossa staining results showed that conditional knockout of ADAM10 in cranial neural crest cells led to embryonic death, craniofacial dysmorphia and bone defects. Furthermore, we demonstrated that impaired mineralization could be triggered by decreased osteoblast differentiation, increased cell death. Overall, these findings show that ADAM10 plays an essential role in craniofacial bone development. -- Highlights: •We firstly reported that ADAM10 was essentially involved in maxillofacial bone development. •ADAM10 cKO mice present craniofacial dysmorphia and bone defects. •Impaired osteoblast differentiation,proliferation and apoptosis underlie the bone deformity.

  17. Neural crest-derived cells with stem cell features can be traced back to multiple lineages in the adult skin

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    C.E. Wong (Christine); S. Paratore (Sabrina); M.T. Dours-Zimmermann (María); T. Rochat (Thierry); T. Pietri (Thomas); U. Suter (Ueli); D. Zimmermann (Dieter); S. Dufour (Sylvie); J.P. Thiery (Joachim); D.N. Meijer (Dies); C. Beermann (Christopher); Y. Barrandon (Yann); L. Sommer (Lukas)

    2006-01-01

    textabstractGiven their accessibility, multipotent skin-derived cells might be useful for future cell replacement therapies. We describe the isolation of multipotent stem cell-like cells from the adult trunk skin of mice and humans that express the neural crest stem cell markers p75 and Sox10 and

  18. Decreased proliferative, migrative and neuro-differentiative potential of postnatal rat enteric neural crest-derived cells during culture in vitro

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    Yu, Hui [Department of Pediatric Surgery, the Second Affiliated Hospital, Xi’an Jiaotong University, No 157, Xi Wu Road, Xi’an 710004, Shaanxi (China); Institute of Neurobiology, Environment and Genes Related to Diseases Key Laboratory of Chinese Ministry of Education, Xi’an Jiaotong University, No 96, Yan Ta Xi Road, Xi’an 710061, Shaanxi (China); Pan, Wei-Kang; Zheng, Bai-Jun; Wang, Huai-Jie [Department of Pediatric Surgery, the Second Affiliated Hospital, Xi’an Jiaotong University, No 157, Xi Wu Road, Xi’an 710004, Shaanxi (China); Chen, Xin-Lin; Liu, Yong [Institute of Neurobiology, Environment and Genes Related to Diseases Key Laboratory of Chinese Ministry of Education, Xi’an Jiaotong University, No 96, Yan Ta Xi Road, Xi’an 710061, Shaanxi (China); Gao, Ya, E-mail: ygao@mail.xjtu.edu.cn [Department of Pediatric Surgery, the Second Affiliated Hospital, Xi’an Jiaotong University, No 157, Xi Wu Road, Xi’an 710004, Shaanxi (China)

    2016-05-01

    A growing body of evidence supports the potential use of enteric neural crest-derived cells (ENCCs) as a cell replacement therapy for Hirschsprung's disease. Based on previous observations of robust propagation of primary ENCCs, as opposed to their progeny, it is suggested that their therapeutic potential after in vitro expansion may be restricted. We therefore examined the growth and differentiation activities and phenotypic characteristics of continuous ENCC cultures. ENCCs were isolated from the intestines of postnatal rats and were identified using an immunocytochemical approach. During continuous ENCC culture expansion, proliferation, migration, apoptosis, and differentiation potentials were monitored. The Cell Counting Kit-8 was used for assessment of ENCC vitality, Transwell inserts for cell migration, immunocytochemistry for cell counts and identification, and flow cytometry for apoptosis. Over six continuous generations, ENCC proliferation potency was reduced and with prolonged culture, the ratio of migratory ENCCs was decreased. The percentage of apoptosis showed an upward trend with prolonged intragenerational culture, but showed a downward trend with prolonged culture of combined generations. Furthermore, the percentage of peripherin{sup +} cells decreased whilst the percentage of GFAP{sup +} cells increased with age. The results demonstrated that alterations in ENCC growth characteristics occur with increased culture time, which may partially account for the poor results of proposed cell therapies. - Highlights: • Differences were identified between primary and daughter ENCCs. • Daughter ENCCs had reduced proliferation, migration and differentiation. • Daughter ENCCs also had increased apoptosis. • These altered characteristics warrant further investigation.

  19. Differentiation defect in neural crest-derived smooth muscle cells in patients with aortopathy associated with bicuspid aortic valves

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    Jiao Jiao

    2016-08-01

    Full Text Available Individuals with bicuspid aortic valves (BAV are at a higher risk of developing thoracic aortic aneurysms (TAA than patients with trileaflet aortic valves (TAV. The aneurysms associated with BAV most commonly involve the ascending aorta and spare the descending aorta. Smooth muscle cells (SMCs in the ascending and descending aorta arise from neural crest (NC and paraxial mesoderm (PM, respectively. We hypothesized defective differentiation of the neural crest stem cells (NCSCs-derived SMCs but not paraxial mesoderm cells (PMCs-derived SMCs contributes to the aortopathy associated with BAV. When induced pluripotent stem cells (iPSCs from BAV/TAA patients were differentiated into NCSC-derived SMCs, these cells demonstrated significantly decreased expression of marker of SMC differentiation (MYH11 and impaired contraction compared to normal control. In contrast, the PMC-derived SMCs were similar to control cells in these aspects. The NCSC-SMCs from the BAV/TAA also showed decreased TGF-β signaling based on phosphorylation of SMAD2, and increased mTOR signaling. Inhibition of mTOR pathway using rapamycin rescued the aberrant differentiation. Our data demonstrates that decreased differentiation and contraction of patient's NCSC-derived SMCs may contribute to that aortopathy associated with BAV.

  20. Depletion of Neural Crest-Derived Cells Leads to Reduction in Plasma Noradrenaline and Alters B Lymphopoiesis.

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    Tsunokuma, Naoki; Yamane, Toshiyuki; Matsumoto, Chiaki; Tsuneto, Motokazu; Isono, Kana; Imanaka-Yoshida, Kyoko; Yamazaki, Hidetoshi

    2017-01-01

    Hematopoietic stem cells and their lymphoid progenitors are supported by the bone marrow (BM) microenvironmental niches composed of various stromal cells and Schwann cells and sympathetic nerve fibers. Although neural crest (NC) cells contribute to the development of all the three, their function in BM is not well understood. In this study, NC-derived cells were ablated with diphtheria toxin in double-transgenic mice expressing NC-specific Cre and Cre-driven diphtheria toxin receptor with yellow fluorescent protein reporter. We found that yellow fluorescent protein-expressing, NC-derived nonhematopoietic cells in BM expressed hematopoietic factors Cxcl12 and stem cell factor The ablation of NC-derived cells led to a significant decrease in B cell progenitors but not in hematopoietic stem cells or myeloid lineage cells in BM. Interestingly, plasma noradrenaline was markedly decreased in these mice. The i.p. administration of 6-hydroxydopamine, a known neurotoxin for noradrenergic neurons, led to a similar phenotype, whereas the administration of a noradrenaline precursor in NC-ablated mice partially rescued this phenotype. Additionally, the continuous administration of adrenergic receptor β antagonists partially decreased the number of B cell progenitors while preserving B lymphopoiesis in vitro. Taken together, our results indicate that NC-derived cell depletion leads to abnormal B lymphopoiesis partially through decreased plasma noradrenaline, suggesting this as a novel mechanism regulated by molecules released by the sympathetic neurons. Copyright © 2016 by The American Association of Immunologists, Inc.

  1. Combination of exogenous cell transplantation and 5-HT{sub 4} receptor agonism induce endogenous enteric neural crest-derived cells in a rat hypoganglionosis model

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    Yu, Hui [Department of Pediatric Surgery, the Second Affiliated Hospital, Xi’an Jiaotong University, No 157, Xi Wu Road, Xi’an 710004, Shaanxi (China); Institute of Neurobiology, Environment and Genes Related to Diseases Key Laboratory of Chinese Ministry of Education, Xi’an Jiaotong University, No 96, Yan Ta Xi Road, Xi’an 710061, Shaanxi (China); Zheng, Bai-Jun; Pan, Wei-Kang; Wang, Huai-Jie; Xie, Chong; Zhao, Yu-Ying [Department of Pediatric Surgery, the Second Affiliated Hospital, Xi’an Jiaotong University, No 157, Xi Wu Road, Xi’an 710004, Shaanxi (China); Chen, Xin-Lin; Liu, Yong [Institute of Neurobiology, Environment and Genes Related to Diseases Key Laboratory of Chinese Ministry of Education, Xi’an Jiaotong University, No 96, Yan Ta Xi Road, Xi’an 710061, Shaanxi (China); Gao, Ya, E-mail: ygao@mail.xjtu.edu.cn [Department of Pediatric Surgery, the Second Affiliated Hospital, Xi’an Jiaotong University, No 157, Xi Wu Road, Xi’an 710004, Shaanxi (China)

    2017-02-01

    Enteric neural crest-derived cells (ENCCs) can migrate into endogenous ganglia and differentiate into progeny cells, and have even partially rescued bowel function; however, poor reliability and limited functional recovery after ENCC transplantation have yet to be addressed. Here, we investigated the induction of endogenous ENCCs by combining exogenous ENCC transplantation with a 5-HT{sub 4} receptor agonist mosapride in a rat model of hypoganglionosis, established by benzalkonium chloride treatment. ENCCs, isolated from the gut of newborn rats, were labeled with a lentiviral eGFP reporter. ENCCs and rats were treated with the 5-HT{sub 4} receptor agonist/antagonist. The labeled ENCCs were then transplanted into the muscular layer of benzalkonium chloride-treated colons. At given days post-intervention, colonic tissue samples were removed for histological analysis. ENCCs and neurons were detected by eGFP expression and immunoreactivity to p75{sup NTR} and peripherin, respectively. eGFP-positive ENCCs and neurons could survive and maintain levels of fluorescence after transplantation. With longer times post-intervention, the number of peripherin-positive cells gradually increased in all groups. Significantly more peripherin-positive cells were found following ENCCs plus mosapride treatment, compared with the other groups. These results show that exogenous ENCCs combined with the 5-HT{sub 4} receptor agonist effectively induced endogenous ENCCs proliferation and differentiation in a rat hypoganglionosis model. - Highlights: • Survival and differentiation of exogenous ENCCs in treated colons. • With longer times post-intervention, the number of ENCCs and their progeny cells gradually increased. • Exogenous ENCCs combined with the 5-HT4 receptor agonist ffectively induced ENCCs proliferation and differentiation.

  2. Direct Genesis of Functional Rodent and Human Schwann Cells from Skin Mesenchymal Precursors

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    Matthew P. Krause

    2014-07-01

    Full Text Available Recent reports of directed reprogramming have raised questions about the stability of cell lineages. Here, we have addressed this issue, focusing upon skin-derived precursors (SKPs, a dermally derived precursor cell. We show by lineage tracing that murine SKPs from dorsal skin originate from mesenchymal and not neural crest-derived cells. These mesenchymally derived SKPs can, without genetic manipulation, generate functional Schwann cells, a neural crest cell type, and are highly similar at the transcriptional level to Schwann cells isolated from the peripheral nerve. This is not a mouse-specific phenomenon, since human SKPs that are highly similar at the transcriptome level can be made from neural crest-derived facial and mesodermally derived foreskin dermis and the foreskin SKPs can make myelinating Schwann cells. Thus, nonneural crest-derived mesenchymal precursors can differentiate into bona fide peripheral glia in the absence of genetic manipulation, suggesting that developmentally defined lineage boundaries are more flexible than widely thought.

  3. Applications of Mesenchymal Stem Cells and Neural Crest Cells in Craniofacial Skeletal Research

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    Satoru Morikawa

    2016-01-01

    Full Text Available Craniofacial skeletal tissues are composed of tooth and bone, together with nerves and blood vessels. This composite material is mainly derived from neural crest cells (NCCs. The neural crest is transient embryonic tissue present during neural tube formation whose cells have high potential for migration and differentiation. Thus, NCCs are promising candidates for craniofacial tissue regeneration; however, the clinical application of NCCs is hindered by their limited accessibility. In contrast, mesenchymal stem cells (MSCs are easily accessible in adults, have similar potential for self-renewal, and can differentiate into skeletal tissues, including bones and cartilage. Therefore, MSCs may represent good sources of stem cells for clinical use. MSCs are classically identified under adherent culture conditions, leading to contamination with other cell lineages. Previous studies have identified mouse- and human-specific MSC subsets using cell surface markers. Additionally, some studies have shown that a subset of MSCs is closely related to neural crest derivatives and endothelial cells. These MSCs may be promising candidates for regeneration of craniofacial tissues from the perspective of developmental fate. Here, we review the fundamental biology of MSCs in craniofacial research.

  4. The role of the mesenchyme in cranial neural fold elevation

    Energy Technology Data Exchange (ETDEWEB)

    Morris-Wiman, J.A.

    1988-01-01

    It has been previously postulated that the expansion of an hyaluronate-rich extracellular matrix in the fold mesenchyme is responsible for neural fold elevation. In this study we provide evidence that such expansions may play an important role in cranial neural fold elevation by pushing the folds towards the dorsal midline to assist in their elevation. For mesenchymal expansion to result in fold elevation, hyaluronate (HA) and mesenchymal cells must be non-randomly distributed within the mesenchyme. Patterns of mesenchymal cell distribution and cell proliferation were analyzed using the computer-assisted method of smoothed spatial averaging. The distribution of Alcian blue-stained and {sup 3}H-glucosamine-labelled HA was also analyzed during cranial neural fold elevation using established image processing techniques. Analysis of the distribution of {sup 3}H-thymidine-labelled mesenchymal cells indicated that differential mitotic activity was not responsible for decreased mesenchymal cell density. Likewise, analysis of distribution patterns of {sup 3}H-glucosamine-labelled HA indicated that decreased HA concentration was not produced by regional differences in HA synthesis. These results suggest that decreases in mesenchymal cell density and HA concentration that occur during neural fold elevation are produced by mesenchymal expansion.

  5. Adipose stromal cells contain phenotypically distinct adipogenic progenitors derived from neural crest.

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    Yoshihiro Sowa

    Full Text Available Recent studies have shown that adipose-derived stromal/stem cells (ASCs contain phenotypically and functionally heterogeneous subpopulations of cells, but their developmental origin and their relative differentiation potential remain elusive. In the present study, we aimed at investigating how and to what extent the neural crest contributes to ASCs using Cre-loxP-mediated fate mapping. ASCs harvested from subcutaneous fat depots of either adult P0-Cre/or Wnt1-Cre/Floxed-reporter mice contained a few neural crest-derived ASCs (NCDASCs. This subpopulation of cells was successfully expanded in vitro under standard culture conditions and their growth rate was comparable to non-neural crest derivatives. Although NCDASCs were positive for several mesenchymal stem cell markers as non-neural crest derivatives, they exhibited a unique bipolar or multipolar morphology with higher expression of markers for both neural crest progenitors (p75NTR, Nestin, and Sox2 and preadipocytes (CD24, CD34, S100, Pref-1, GATA2, and C/EBP-delta. NCDASCs were able to differentiate into adipocytes with high efficiency but their osteogenic and chondrogenic potential was markedly attenuated, indicating their commitment to adipogenesis. In vivo, a very small proportion of adipocytes were originated from the neural crest. In addition, p75NTR-positive neural crest-derived cells were identified along the vessels within the subcutaneous adipose tissue, but they were negative for mural and endothelial markers. These results demonstrate that ASCs contain neural crest-derived adipocyte-restricted progenitors whose phenotype is distinct from that of non-neural crest derivatives.

  6. Adult bone marrow neural crest stem cells and mesenchymal stem cells are not able to replace lost neurons in acute MPTP-lesioned mice.

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    Virginie Neirinckx

    Full Text Available Adult bone marrow stroma contains multipotent stem cells (BMSC that are a mixed population of mesenchymal and neural-crest derived stem cells. Both cells are endowed with in vitro multi-lineage differentiation abilities, then constituting an attractive and easy-available source of material for cell therapy in neurological disorders. Whereas the in vivo integration and differentiation of BMSC in neurons into the central nervous system is currently matter of debate, we report here that once injected into the striatum of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP-treated mice, pure populations of either bone marrow neural crest stem cells (NCSC or mesenchymal stem cells (MSC survived only transiently into the lesioned brain. Moreover, they do not migrate through the brain tissue, neither modify their initial phenotype, while no recovery of the dopaminergic system integrity was observed. Consequently, we tend to conclude that MSC/NCSC are not able to replace lost neurons in acute MPTP-lesioned dopaminergic system through a suitable integration and/or differentiation process. Altogether with recent data, it appears that neuroprotective, neurotrophic and anti-inflammatory features characterizing BMSC are of greater interest as regards CNS lesions management.

  7. Treatment of spinal cord injury: a review of engineering using neural and mesenchymal stem cells.

    Science.gov (United States)

    Mortazavi, Martin M; Harmon, Olivia A; Adeeb, Nimer; Deep, Aman; Tubbs, R Shane

    2015-01-01

    Over time, various treatment modalities for spinal cord injury have been trialed, including pharmacological and nonpharmacological methods. Among these, replacement of the injured neural and paraneural tissues via cellular transplantation of neural and mesenchymal stem cells has been the most attractive. Extensive experimental studies have been done to identify the safety and effectiveness of this transplantation in animal and human models. Herein, we review the literature for studies conducted, with a focus on the human-related studies, recruitment, isolation, and transplantation, of these multipotent stem cells, and associated outcomes. © 2014 Wiley Periodicals, Inc.

  8. Expression of Neural Markers by Undifferentiated Mesenchymal-Like Stem Cells from Different Sources

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    Dana Foudah

    2014-01-01

    Full Text Available The spontaneous expression of neural markers, already demonstrated in bone marrow (BM mesenchymal stem cells (MSCs, has been considered as evidence of the MSCs’ predisposition to differentiate toward neural lineages, supporting their use in stem cell-based therapy for neural repair. In this study we have evaluated, by immunocytochemistry, immunoblotting, and flow cytometry experiments, the expression of neural markers in undifferentiated MSCs from different sources: human adipose stem cells (hASCs, human skin-derived mesenchymal stem cells (hS-MSCs, human periodontal ligament stem cells (hPDLSCs, and human dental pulp stem cells (hDPSCs. Our results demonstrate that the neuronal markers βIII-tubulin and NeuN, unlike other evaluated markers, are spontaneously expressed by a very high percentage of undifferentiated hASCs, hS-MSCs, hPDLSCs, and hDPSCs. Conversely, the neural progenitor marker nestin is expressed only by a high percentage of undifferentiated hPDLSCs and hDPSCs. Our results suggest that the expression of βIII-tubulin and NeuN could be a common feature of stem cells and not exclusive to neuronal cells. This could result in a reassessment of the use of βIII-tubulin and NeuN as the only evidence proving neuronal differentiation. Further studies will be necessary to elucidate the relevance of the spontaneous expression of these markers in stem cells.

  9. Transplantation of placenta-derived mesenchymal stem cell-induced neural stem cells to treat spinal cord injury.

    Science.gov (United States)

    Li, Zhi; Zhao, Wei; Liu, Wei; Zhou, Ye; Jia, Jingqiao; Yang, Lifeng

    2014-12-15

    Because of their strong proliferative capacity and multi-potency, placenta-derived mesenchymal stem cells have gained interest as a cell source in the field of nerve damage repair. In the present study, human placenta-derived mesenchymal stem cells were induced to differentiate into neural stem cells, which were then transplanted into the spinal cord after local spinal cord injury in rats. The motor functional recovery and pathological changes in the injured spinal cord were observed for 3 successive weeks. The results showed that human placenta-derived mesenchymal stem cells can differentiate into neuron-like cells and that induced neural stem cells contribute to the restoration of injured spinal cord without causing transplant rejection. Thus, these cells promote the recovery of motor and sensory functions in a rat model of spinal cord injury. Therefore, human placenta-derived mesenchymal stem cells may be useful as seed cells during the repair of spinal cord injury.

  10. Differentiation of Equine Mesenchymal Stromal Cells into Cells of Neural Lineage: Potential for Clinical Applications

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    Claudia Cruz Villagrán

    2014-01-01

    Full Text Available Mesenchymal stromal cells (MSCs are able to differentiate into extramesodermal lineages, including neurons. Positive outcomes were obtained after transplantation of neurally induced MSCs in laboratory animals after nerve injury, but this is unknown in horses. Our objectives were to test the ability of equine MSCs to differentiate into cells of neural lineage in vitro, to assess differences in morphology and lineage-specific protein expression, and to investigate if horse age and cell passage number affected the ability to achieve differentiation. Bone marrow-derived MSCs were obtained from young and adult horses. Following demonstration of stemness, MSCs were neurally induced and microscopically assessed at different time points. Results showed that commercially available nitrogen-coated tissue culture plates supported proliferation and differentiation. Morphological changes were immediate and all the cells displayed a neural crest-like cell phenotype. Expression of neural progenitor proteins, was assessed via western blot or immunofluorescence. In our study, MSCs generated from young and middle-aged horses did not show differences in their ability to undergo differentiation. The effect of cell passage number, however, is inconsistent and further experiments are needed. Ongoing work is aimed at transdifferentiating these cells into Schwann cells for transplantation into a peripheral nerve injury model in horses.

  11. Human dental follicle cells express embryonic, mesenchymal and neural stem cells markers.

    Science.gov (United States)

    Lima, Rodrigo Lopes; Holanda-Afonso, Rosenilde Carvalho; Moura-Neto, Vivaldo; Bolognese, Ana Maria; DosSantos, Marcos Fabio; Souza, Margareth Maria

    2017-01-01

    This study was conducted to identify and characterize dental follicle stem cells (DFSCs) by analyzing expression of embryonic, mesenchymal and neural stem cells surface markers. Design Dental follicle cells (DFCs) were evaluated by immunocytochemistry using embryonic stem cells markers (OCT4 and SOX2), mesenchmal stem cells (MSCs) markers (Notch1, active Notch1, STRO, CD44, HLA-ABC, CD90), neural stem cells markers (Nestin and β-III-tubulin), neural crest stem cells (NCSCs) markers (p75 and HNK1) and a glial cells marker (GFAP). RT-PCR was performed to identify the expression of OCT4 and NANOG in DFCs and dental follicle tissue. Immunocytochemistry and RT-PCR analysis revealed that a significant proportion of the DFCs evaluated expressed human embryonic stem cells marker OCT4 (75%) whereas NANOG was weakly expressed. A considerable amount of MSCs (90%) expressed Notch1, STRO, CD44 and HLA-ABC. However, they were weakly positive for CD90. Moreover, it was possible to demonstrate that dental follicle contains a significant proportion of neural stem/progenitors cells, expressing β-III-tubulin (90%) and nestin (70%). Interestingly, immunocytochemistry showed DFCs positive for p75 (50%), HNK1 (cells. This is the first study reporting the presence of NCSCs and glial-like cells in the dental follicle. The results of the present study suggest the occurrence of heterogeneous populations of stem cells, particularly neural stem/progenitor cells, in the dental follicle, Therefore, the human dental follicle might be a promising source of adult stem cells for regenerative purposes. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Neural crest delamination and migration: from epithelium-to-mesenchyme transition to collective cell migration.

    Science.gov (United States)

    Theveneau, Eric; Mayor, Roberto

    2012-06-01

    After induction and specification in the ectoderm, at the border of the neural plate, the neural crest (NC) population leaves its original territory through a delamination process. Soon afterwards, the NC cells migrate throughout the embryo and colonize a myriad of tissues and organs where they settle and differentiate. The delamination involves a partial or complete epithelium-to-mesenchyme transition (EMT) regulated by a complex network of transcription factors including several proto-oncogenes. Studying the relationship between these genes at the time of emigration, and their individual or collective impact on cell behavior, provides valuable information about their role in EMT in other contexts such as cancer metastasis. During migration, NC cells are exposed to large number of positive and negative regulators that control where they go by generating permissive and restricted areas and by modulating their motility and directionality. In addition, as most NC cells migrate collectively, cell-cell interactions play a crucial role in polarizing the cells and interpreting external cues. Cell cooperation eventually generates an overall polarity to the population, leading to directional collective cell migration. This review will summarize our current knowledge on delamination, EMT and migration of NC cells using key examples from chicken, Xenopus, zebrafish and mouse embryos. Given the similarities between neural crest migration and cancer invasion, these cells may represent a useful model for understanding the mechanisms of metastasis. Copyright © 2011 Elsevier Inc. All rights reserved.

  13. Sox2 acts as a rheostat of epithelial to mesenchymal transition during neural crest development

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    Nikolaos eMandalos

    2014-09-01

    Full Text Available Precise control of self-renewal and differentiation of progenitor cells into the cranial neural crest (CNC pool ensures proper head development, guided by signaling pathways such as BMPs, FGFs, Shh and Notch. Here, we show that murine Sox2 plays an essential role in controlling progenitor cell behavior during craniofacial development. A Conditional by Inversion Sox2 allele (Sox2COIN has been employed to generate an epiblast ablation of Sox2 function (Sox2EpINV. Sox2EpINV/+(H haploinsufficient and conditional (Sox2EpINV/mosaic mutant embryos proceed beyond gastrulation and die around E11. These mutant embryos exhibit severe anterior malformations, with hydrocephaly and frontonasal truncations, which could be attributed to the deregulation of CNC progenitor cells during their epithelial to mesenchymal transition. This irregularity results in an exacerbated and aberrant migration of Sox10+ NCC in the branchial arches and frontonasal process of the Sox2 mutant embryos. These results suggest a novel role for Sox2 as a regulator of the epithelial to mesenchymal transitions that are important for the cell flow in the developing head.

  14. Neural differentiation potential of human bone marrow-derived mesenchymal stromal cells: misleading marker gene expression

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    Montzka Katrin

    2009-03-01

    Full Text Available Abstract Background In contrast to pluripotent embryonic stem cells, adult stem cells have been considered to be multipotent, being somewhat more restricted in their differentiation capacity and only giving rise to cell types related to their tissue of origin. Several studies, however, have reported that bone marrow-derived mesenchymal stromal cells (MSCs are capable of transdifferentiating to neural cell types, effectively crossing normal lineage restriction boundaries. Such reports have been based on the detection of neural-related proteins by the differentiated MSCs. In order to assess the potential of human adult MSCs to undergo true differentiation to a neural lineage and to determine the degree of homogeneity between donor samples, we have used RT-PCR and immunocytochemistry to investigate the basal expression of a range of neural related mRNAs and proteins in populations of non-differentiated MSCs obtained from 4 donors. Results The expression analysis revealed that several of the commonly used marker genes from other studies like nestin, Enolase2 and microtubule associated protein 1b (MAP1b are already expressed by undifferentiated human MSCs. Furthermore, mRNA for some of the neural-related transcription factors, e.g. Engrailed-1 and Nurr1 were also strongly expressed. However, several other neural-related mRNAs (e.g. DRD2, enolase2, NFL and MBP could be identified, but not in all donor samples. Similarly, synaptic vesicle-related mRNA, STX1A could only be detected in 2 of the 4 undifferentiated donor hMSC samples. More significantly, each donor sample revealed a unique expression pattern, demonstrating a significant variation of marker expression. Conclusion The present study highlights the existence of an inter-donor variability of expression of neural-related markers in human MSC samples that has not previously been described. This donor-related heterogeneity might influence the reproducibility of transdifferentiation protocols as

  15. The effect of lithium on hematopoietic, mesenchymal and neural stem cells.

    Science.gov (United States)

    Ferensztajn-Rochowiak, Ewa; Rybakowski, Janusz K

    2016-04-01

    Lithium has been used in modern psychiatry for more than 65 years, constituting a cornerstone for the long-term treatment of bipolar disorder. A number of biological properties of lithium have been discovered, including its hematological, antiviral and neuroprotective effects. In this article, a systematic review of the effect of lithium on hematopoietic, mesenchymal and neural stem cells is presented. The beneficial effects of lithium on the level of hematopoietic stem cells (HSC) and growth factors have been reported since 1970s. Lithium improves homing of stem cells, the ability to form colonies and HSC self-renewal. Lithium also exerts a favorable influence on the proliferation and maintenance of mesenchymal stem cells (MSC). Studies on the effect of lithium on neurogenesis have indicated an increased proliferation of progenitor cells in the dentate gyrus of the hippocampus and enhanced mitotic activity of Schwann cells. This may be connected with the neuroprotective and neurotrophic effects of lithium, reflected in an improvement in synaptic plasticity promoting cell survival and inhibiting apoptosis. In clinical studies, lithium treatment increases cerebral gray matter, mainly in the frontal lobes, hippocampus and amygdala. Recent findings also suggest that lithium may reduce the risk of dementia and exert a beneficial effect in neurodegenerative diseases. The most important mediators and signaling pathways of lithium action are the glycogen synthase kinase-3 and Wnt/β-catenin pathways. Recently, to study of bipolar disorder pathogenesis and the mechanism of lithium action, the induced pluripotent stem cells (iPSC) obtained from bipolar patients have been used. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  16. Grainyhead-like 2 downstream targets act to suppress epithelial-to-mesenchymal transition during neural tube closure.

    Science.gov (United States)

    Ray, Heather J; Niswander, Lee A

    2016-04-01

    The transcription factor grainyhead-like 2 (GRHL2) is expressed in non-neural ectoderm (NNE) and Grhl2 loss results in fully penetrant cranial neural tube defects (NTDs) in mice. GRHL2 activates expression of several epithelial genes; however, additional molecular targets and functional processes regulated by GRHL2 in the NNE remain to be determined, as well as the underlying cause of the NTDs in Grhl2 mutants. Here, we find that Grhl2 loss results in abnormal mesenchymal phenotypes in the NNE, including aberrant vimentin expression and increased cellular dynamics that affects the NNE and neural crest cells. The resulting loss of NNE integrity contributes to an inability of the cranial neural folds to move toward the midline and results in NTD. Further, we identified Esrp1, Sostdc1, Fermt1, Tmprss2 and Lamc2 as novel NNE-expressed genes that are downregulated in Grhl2 mutants. Our in vitro assays show that they act as suppressors of the epithelial-to-mesenchymal transition (EMT). Thus, GRHL2 promotes the epithelial nature of the NNE during the dynamic events of neural tube formation by both activating key epithelial genes and actively suppressing EMT through novel downstream EMT suppressors. © 2016. Published by The Company of Biologists Ltd.

  17. The role of the mesenchyme in mouse neural fold elevation. II. Patterns of hyaluronate synthesis and distribution in embryos developing in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Morris-Wiman, J.; Brinkley, L.L. (Univ. of Michigan Medical School, Ann Arbor (USA))

    1990-06-01

    Hyaluronate (HA) distribution patterns were examined in the cranial mesenchyme underlying the mesencephalic neural folds of mouse embryos maintained in roller tube culture. Using standard image-processing techniques, the digitized images of Alcian blue-stained or 3H-glucosamine-labeled sections digested with an enzyme specific for HA, were subtracted from adjacent, undigested sections. The resultant difference picture images (DPI) accurately depicted the distribution of stained or labeled HA within the cranial mesenchyme. 3H-glucosamine-labeled HA was distributed uniformly throughout the cranial mesenchyme as 12, 18, and 24 hr of culture. By contrast, the mesenchyme was uniformly stained with Alcian blue at 12 hr, but stain intensity decreased in the central regions of the mesenchyme at 18 and 24 hr. HA distribution patterns were also examined in the cranial mesenchyme of embryos cultured in the presence of diazo-oxo-norleucine (DON), a glutamine analogue that inhibits glycosaminoglycan and glycoprotein synthesis. In DON-treated mesenchyme, Alcian blue staining of HA was decreased from that in controls at 12, 18, and 24 hr. However, incorporation of 3H-glucosamine into HA was increased. The distribution of labeled HA within treated mesenchyme as 12, 18, and 24 hr resembled that in controls at 12 hr. These results indicate that the distribution of HA within the cranial mesenchyme of normal mouse embryos during neural fold elevation and convergence is not determined solely by regional differences in HA synthesis. We propose that HA distribution patterns result from the expansion of the HA-rich extracellular matrix of the central mesenchyme regions. This expansion may play a major role in fold elevation. These results also suggest that DON treatment reversibly inhibits HA synthesis.

  18. Sonic hedgehog regulation of Foxf2 promotes cranial neural crest mesenchyme proliferation and is disrupted in cleft lip morphogenesis.

    Science.gov (United States)

    Everson, Joshua L; Fink, Dustin M; Yoon, Joon Won; Leslie, Elizabeth J; Kietzman, Henry W; Ansen-Wilson, Lydia J; Chung, Hannah M; Walterhouse, David O; Marazita, Mary L; Lipinski, Robert J

    2017-06-01

    Cleft lip is one of the most common human birth defects, yet our understanding of the mechanisms that regulate lip morphogenesis is limited. Here, we show in mice that sonic hedgehog (Shh)-induced proliferation of cranial neural crest cell (cNCC) mesenchyme is required for upper lip closure. Gene expression profiling revealed a subset of Forkhead box (Fox) genes that are regulated by Shh signaling during lip morphogenesis. During cleft pathogenesis, reduced proliferation in the medial nasal process mesenchyme paralleled the domain of reduced Foxf2 and Gli1 expression. SHH ligand induction of Foxf2 expression was dependent upon Shh pathway effectors in cNCCs, while a functional GLI-binding site was identified downstream of Foxf2 Consistent with the cellular mechanism demonstrated for cleft lip pathogenesis, we found that either SHH ligand addition or FOXF2 overexpression is sufficient to induce cNCC proliferation. Finally, analysis of a large multi-ethnic human population with cleft lip identified clusters of single-nucleotide polymorphisms in FOXF2 These data suggest that direct targeting of Foxf2 by Shh signaling drives cNCC mesenchyme proliferation during upper lip morphogenesis, and that disruption of this sequence results in cleft lip. © 2017. Published by The Company of Biologists Ltd.

  19. Stage-specific control of neural crest stem cell proliferation by the small rho GTPases Cdc42 and Rac1

    DEFF Research Database (Denmark)

    Fuchs, Sebastian; Herzog, Dominik; Sumara, Grzegorz

    2009-01-01

    The neural crest (NC) generates a variety of neural and non-neural tissues during vertebrate development. Both migratory NC cells and their target structures contain cells with stem cell features. Here we show that these populations of neural crest-derived stem cells (NCSCs) are differentially re...

  20. Electromagnetic fields induce neural differentiation of human bone marrow derived mesenchymal stem cells via ROS mediated EGFR activation.

    Science.gov (United States)

    Park, Jeong-Eun; Seo, Young-Kwon; Yoon, Hee-Hoon; Kim, Chan-Wha; Park, Jung-Keug; Jeon, Songhee

    2013-03-01

    Even though the inducing effect of electromagnetic fields (EMF) on the neural differentiation of human bone marrow mesenchymal stem cells (hBM-MSCs) is a distinctive, the underlying mechanism of differentiation remains unclear. To find out the signaling pathways involved in the neural differentiation of BM-MSCs by EMF, we examined the CREB phosphorylation and Akt or ERK activation as an upstream of CREB. In hBM-MSCs treated with ELF-EMF (50 Hz, 1 mT), the expression of neural markers such as NF-L, MAP2, and NeuroD1 increased at 6 days and phosphorylation of Akt and CREB but not ERK increased at 90 min in BM-MSCs. Moreover, EMF increased phosphorylation of epidermal growth factor receptor (EGFR) as an upstream receptor tyrosine kinase of PI3K/Akt at 90 min. It has been well documented that ELF-MF exposure may alter cellular processes by increasing intracellular reactive oxygen species (ROS) concentrations. Thus, we examined EMF-induced ROS production in BM-MSCs. Moreover, pretreatment with a ROS scavenger, N-acetylcystein, and an EGFR inhibitor, AG-1478, prevented the phosphorylation of EGFR and downstream molecules. These results suggest that EMF induce neural differentiation through activation of EGFR signaling and mild generation of ROS. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. Are neural crest stem cells the missing link between hematopoietic and neurogenic niches?

    Directory of Open Access Journals (Sweden)

    Cécile eCoste

    2015-06-01

    Full Text Available Hematopoietic niches are defined as cellular and molecular microenvironments that regulate hematopoietic stem cell (HSC function together with stem cell autonomous mechanisms. Many different cell types have been characterized as contributors to the formation of HSC niches, such as osteoblasts, endothelial cells, Schwann cells, and mesenchymal progenitors. These mesenchymal progenitors have themselves been classified as CXC chemokine ligand (CXCL12-abundant reticular (CAR cells, stem cell factor expressing cells, or nestin-positive mesenchymal stem cells (MSCs, which have been recently identified as neural crest-derived cells (NCSCs. Together, these cells are spatially associated with HSCs and believed to provide appropriate microenvironments for HSC self-renewal, differentiation, mobilization and hibernation both by cell-to-cell contact and soluble factors. Interestingly, it appears that regulatory pathways governing the hematopoietic niche homeostasis are operating in the neurogenic niche as well. Therefore, this review paper aims to compare both the regulation of hematopoietic and neurogenic niches, in order to highlight the role of NCSCs and nervous system components in the development and the regulation of the hematopoietic system.

  2. Multiple cranial organ defects after conditionally knocking out Fgf10 in the neural crest

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    Tathyane H.N. Teshima

    2016-10-01

    Full Text Available Fgf10 is necessary for the development of a number of organs that fail to develop or are reduced in size in the null mutant. Here we have knocked out Fgf10 specifically in the neural crest driven by Wnt1cre. The Wnt1creFgf10fl/fl mouse phenocopies many of the null mutant defects, including cleft palate, loss of salivary glands and ocular glands, highlighting the neural crest origin of the Fgf10 expressing mesenchyme surrounding these organs. In contrast tissues such as the limbs and lungs, where Fgf10 is expressed by the surrounding mesoderm, were unaffected, as was the pituitary gland where Fgf10 is expressed by the neuroepithelium. The circumvallate papilla of the tongue formed but was hypoplastic in the conditional and Fgf10 null embryos, suggesting that other sources of FGF can compensate in development of this structure. The tracheal cartilage rings showed normal patterning in the conditional knockout, indicating that the source of Fgf10 for this tissue is mesodermal, which was confirmed using Wnt1cre-dtTom to lineage trace the boundary of the neural crest in this region. The thyroid, thymus and parathyroid glands surrounding the trachea were present but hypoplastic in the conditional mutant, indicating that a neighbouring source of mesodermal Fgf10 might be able to partially compensate for loss of neural crest derived Fgf10.

  3. Neural metabolite changes in corpus striatum after rat multipotent mesenchymal stem cells transplanted in hemiparkinsonian rats by magnetic resonance spectroscopy.

    Science.gov (United States)

    Fu, Wenyu; Zheng, Zhijuan; Zhuang, Wenxin; Chen, Dandan; Wang, Xiaocui; Sun, Xihe; Wang, Xin

    2013-12-01

    To investigate the biochemical changes in striatum after rat bone marrow mesenchymal stem cells (MSCs) were transplanted into hemiparkinsonian rats and to further confirm the therapeutic effects of rat MSCs for Parkinson's disease (PD). 5-bromo-2-deoxyuridine (BrdU)-labeled MSCs were transplanted into the corpus striatum of the 6-hydroxydopamine (6-OHDA)-injected side of six PD model rats. Before and 8 weeks after MSC transplantation, ethological changes in PD rats were assessed. The expression of tyrosine hydroxylase (TH) in substantia nigra (SN) and striatum were measured using immunohistochemical methods. The differentiation of MSCs was detected by double immunofluorescence techniques. The concentrations of neural metabolites of N-acetylaspartate (NAA), choline (Cho) and creatine (Cr) were measured by ¹H-magnetic resonance spectroscopy (MRS). Relative concentrations of NAA/Cr and Cho/Cr were calculated. The behavior of PD rats in rotarod tests improved, and there were statistical differences in TH-positive cells in SN and TH-positive terminals in striatum after the transplantation of BrdU-labeled MSCs. Transplanted MSCs differentiated into MAP-2-positive neurons. Especially compared with pre-MSC transplantation, the neural metabolite NAA/Cr ratio of the 6-OHDA-injected side of the striatum increased (P rats.

  4. Nestin-positive mesenchymal stem cells favour the astroglial lineage in neural progenitors and stem cells by releasing active BMP4

    Directory of Open Access Journals (Sweden)

    Leprince Pierre

    2004-09-01

    Full Text Available Abstract Background Spontaneous repair is limited after CNS injury or degeneration because neurogenesis and axonal regrowth rarely occur in the adult brain. As a result, cell transplantation has raised much interest as potential treatment for patients with CNS lesions. Several types of cells have been considered as candidates for such cell transplantation and replacement therapies. Foetal brain tissue has already been shown to have significant effects in patients with Parkinson's disease. Clinical use of the foetal brain tissue is, however, limited by ethical and technical problems as it requires high numbers of grafted foetal cells and immunosuppression. Alternatively, several reports suggested that mesenchymal stem cells, isolated from adult bone marrow, are multipotent cells and could be used in autograft approach for replacement therapies. Results In this study, we addressed the question of the possible influence of mesenchymal stem cells on neural stem cell fate. We have previously reported that adult rat mesenchymal stem cells are able to express nestin in defined culture conditions (in the absence of serum and after 25 cell population doublings and we report here that nestin-positive (but not nestin-negative mesenchymal stem cells are able to favour the astroglial lineage in neural progenitors and stem cells cultivated from embryonic striatum. The increase of the number of GFAP-positive cells is associated with a significant decrease of the number of Tuj1- and O4-positive cells. Using quantitative RT-PCR, we demonstrate that mesenchymal stem cells express LIF, CNTF, BMP2 and BMP4 mRNAs, four cytokines known to play a role in astroglial fate decision. In this model, BMP4 is responsible for the astroglial stimulation and oligodendroglial inhibition, as 1 this cytokine is present in a biologically-active form only in nestin-positive mesenchymal stem cells conditioned medium and 2 anti-BMP4 antibodies inhibit the nestin-positive mesenchymal

  5. Differentiation of reprogrammed human adipose mesenchymal stem cells toward neural cells with defined transcription factors.

    Science.gov (United States)

    Qu, Xinjian; Liu, Tianqing; Song, Kedong; Li, Xiangqin; Ge, Dan

    2013-10-04

    Somatic cell reprogramming may become a powerful approach to generate specific human cell types for cell-fate determination studies and potential transplantation therapies of neurological diseases. Here we report a reprogramming methodology with which human adipose stem cells (hADSCs) can be differentiated into neural cells. After being reprogrammed with polycistronic plasmid carrying defined factor OCT3/4, SOX2, KLF4 and c-MYC, and further treated with neural induce medium, the hADSCs switched to differentiate toward neural cell lineages. The generated cells had normal karyotypes and exogenous vector sequences were not inserted in the genomes. Therefore, this cell lineage conversion methodology bypasses the risk of mutation and gene instability, and provides a novel strategy to obtain patient-specific neural cells for basic research and therapeutic application. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. The active principle region of Buyang Huanwu decoction induced differentiation of bone marrow-derived mesenchymal stem cells into neural-like cells

    Science.gov (United States)

    Zheng, Jinghui; Wan, Yi; Chi, Jianhuai; Shen, Dekai; Wu, Tingting; Li, Weimin; Du, Pengcheng

    2012-01-01

    The present study induced in vitro-cultured passage 4 bone marrow-derived mesenchymal stem cells to differentiate into neural-like cells with a mixture of alkaloid, polysaccharide, aglycone, glycoside, essential oils, and effective components of Buyang Huanwu decoction (active principle region of decoction for invigorating yang for recuperation). After 28 days, nestin and neuron-specific enolase were expressed in the cytoplasm. Reverse transcription-PCR and western blot analyses showed that nestin and neuron-specific enolase mRNA and protein expression was greater in the active principle region group compared with the original formula group. Results demonstrated that the active principle region of Buyang Huanwu decoction induced greater differentiation of rat bone marrow-derived mesenchymal stem cells into neural-like cells in vitro than the original Buyang Huanwu decoction formula. PMID:25806066

  7. Combined effect of pulsed electromagnetic field and sound wave on In vitro and In vivo neural differentiation of human mesenchymal stem cells.

    Science.gov (United States)

    Choi, Yun-Kyong; Urnukhsaikhan, Enerelt; Yoon, Hee-Hoon; Seo, Young-Kwon; Cho, Hyunjin; Jeong, Jong-Seob; Kim, Soo-Chan; Park, Jung-Keug

    2017-01-01

    Biophysical wave stimulus has been used as an effective tool to promote cellular maturation and differentiation in the construction of engineered tissue. Pulsed electromagnetic fields (PEMFs) and sound waves have been selected as effective stimuli that can promote neural differentiation. The aim of this study was to investigate the synergistic effect of PEMFs and sound waves on the neural differentiation potential in vitro and in vivo using human bone marrow mesenchymal stem cells (hBM-MSCs). In vitro, neural-related genes in hBM-MSCs were accelerated by the combined exposure to both waves more than by individual exposure to PEMFs or sound waves. The combined wave also up-regulated the expression of neural and synaptic-related proteins in a three-dimensional (3-D) culture system through the phosphorylation of extracellular signal-related kinase. In a mouse model of photochemically induced ischemia, exposure to the combined wave reduced the infarction volume and improved post-injury behavioral activity. These results indicate that a combined stimulus of biophysical waves, PEMFs and sound can enhance and possibly affect the differentiation of MSCs into neural cells. Our study is meaningful for highlighting the potential of combined wave for neurogenic effects and providing new therapeutic approaches for neural cell therapy. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 33:201-211, 2017. © 2016 American Institute of Chemical Engineers.

  8. LNGFR(+)THY-1(+) human pluripotent stem cell-derived neural crest-like cells have the potential to develop into mesenchymal stem cells.

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    Ouchi, Takehito; Morikawa, Satoru; Shibata, Shinsuke; Fukuda, Kimiko; Okuno, Hironobu; Fujimura, Takumi; Kuroda, Tatsuo; Ohyama, Manabu; Akamatsu, Wado; Nakagawa, Taneaki; Okano, Hideyuki

    2016-12-01

    Mesenchymal stem cells (MSCs) are defined as non-hematopoietic, plastic-adherent, self-renewing cells that are capable of tri-lineage differentiation into bone, cartilage or fat in vitro. Thus, MSCs are promising candidates for cell-based medicine. However, classifications of MSCs have been defined retrospectively; moreover, this conventional criterion may be inaccurate due to contamination with other hematopoietic lineage cells. Human MSCs can be enriched by selection for LNGFR and THY-1, and this population may be analogous to murine PDGFRα(+)Sca-1(+) cells, which are developmentally derived from neural crest cells (NCCs). Murine NCCs were labeled by fluorescence, which provided definitive proof of neural crest lineage, however, technical considerations prevent the use of a similar approach to determine the origin of human LNGFR(+)THY-1(+) MSCs. To further clarify the origin of human MSCs, human embryonic stem cells (ESCs) and human induced pluripotent stem cells (iPSCs) were used in this study. Under culture conditions required for the induction of neural crest cells, human ESCs and iPSCs-derived cells highly expressed LNGFR and THY-1. These LNGFR(+)THY-1(+) neural crest-like cells, designated as LT-NCLCs, showed a strong potential to differentiate into both mesenchymal and neural crest lineages. LT-NCLCs proliferated to form colonies and actively migrated in response to serum concentration. Furthermore, we transplanted LT-NCLCs into chick embryos, and traced their potential for survival, migration and differentiation in the host environment. These results suggest that LNGFR(+)THY-1(+) cells identified following NCLC induction from ESCs/iPSCs shared similar potentials with multipotent MSCs. Copyright © 2016 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.

  9. The neural plasticity of early-passage human bone marrow-derived mesenchymal stem cells and their modulation with chromatin-modifying agents.

    Science.gov (United States)

    Zhang, Zhiying; Alexanian, Arshak R

    2014-05-01

    Mesenchymal stem cells (MSCs) in their immature state express a variety of genes of the three germ layers at relatively low or moderate levels that might explain their phenomenal plasticity. Numerous recent studies have demonstrated that under the appropriate conditions in vitro and in vivo the expression of different sets of these genes can be upregulated, turning MSCs into variety of cell lineages of mesodermal, ectodermal and endodermal origin. While transdifferentiation of MSCs is still controversial, these unique properties make MSCs an ideal autologous source of easily reprogrammable cells. Recently, using the approach of cell reprogramming by biological active compounds that interfere with chromatin structure and function, as well as with specific signalling pathways that promote neural fate commitment, we have been able to generate neural-like cells from human bone marrow (BM)-derived MSCs (hMSCs). However, the efficiency of neural transformation of hMSCs induced by this approach gradually declined with passaging. To elucidate the mechanisms that underlie the higher plasticity of early-passage hMSCs, comparative analysis of the expression levels of several pluripotent and neural genes was conducted for early- and late-passage hMSCs. The results demonstrated that early-passage hMSCs expressed the majority of these genes at low and moderate levels that gradually declined at late passages. Neural induction further increased the expression of some of these genes in hMSCs, accompanied by morphological changes into neural-like cells. We concluded that low and moderate expression of several pluripotent and neural genes in early-passage hMSCs could explain their higher plasticity and pliability for neural induction. Copyright © 2012 John Wiley & Sons, Ltd.

  10. Transplanted neurally modified bone marrow-derived mesenchymal stem cells promote tissue protection and locomotor recovery in spinal cord injured rats.

    Science.gov (United States)

    Alexanian, Arshak R; Fehlings, Michael G; Zhang, Zhiying; Maiman, Dennis J

    2011-01-01

    Stem cell-based therapy for repair and replacement of lost neural cells is a promising treatment for central nervous system (CNS) diseases. Bone marrow (BM)-derived mesenchymal stem cells (MSCs) can differentiate into neural phenotypes and be isolated and expanded for autotransplantation with no risk of rejection. The authors examined whether transplanted neurally induced human MSCs (NI hMSCs), developed by a new procedure, can survive, differentiate, and promote tissue protection and functional recovery in injured spinal cord (ISC) rats. Neural induction was achieved by exposing cells simultaneously to inhibitors of DNA methylation, histone deacetylation, and pharmacological agents that increased cAMP levels. Three groups of adult female Sprague-Dawley rats were injected immediately rostral and caudal to the midline lesion with phosphate-buffered saline, MSCs, or NI hMSCs, 1 week after a spinal cord impact injury at T-8. Functional outcome was measured using the Basso Beattie Bresnahan (BBB) locomotor rating scale and thermal sensitivity test on a weekly basis up to 12 weeks postinjury. Graft integration and anatomy of spinal cord was assessed by stereological, histochemical, and immunohistochemical techniques. The transplanted NI hMSCs survived, differentiated, and significantly improved locomotor recovery of ISC rats. Transplantation also reduced the volume of lesion cavity and white matter loss. This method of hMSC modification may provide an alternative source of autologous adult stem cells for CNS repair.

  11. Polypyrrole/Alginate Hybrid Hydrogels: Electrically Conductive and Soft Biomaterials for Human Mesenchymal Stem Cell Culture and Potential Neural Tissue Engineering Applications.

    Science.gov (United States)

    Yang, Sumi; Jang, LindyK; Kim, Semin; Yang, Jongcheol; Yang, Kisuk; Cho, Seung-Woo; Lee, Jae Young

    2016-11-01

    Electrically conductive biomaterials that can efficiently deliver electrical signals to cells or improve electrical communication among cells have received considerable attention for potential tissue engineering applications. Conductive hydrogels are desirable particularly for neural applications, as they can provide electrical signals and soft microenvironments that can mimic native nerve tissues. In this study, conductive and soft polypyrrole/alginate (PPy/Alg) hydrogels are developed by chemically polymerizing PPy within ionically cross-linked alginate hydrogel networks. The synthesized hydrogels exhibit a Young's modulus of 20-200 kPa. Electrical conductance of the PPy/Alg hydrogels could be enhanced by more than one order of magnitude compared to that of pristine alginate hydrogels. In vitro studies with human bone marrow-derived mesenchymal stem cells (hMSCs) reveal that cell adhesion and growth are promoted on the PPy/Alg hydrogels. Additionally, the PPy/Alg hydrogels support and greatly enhance the expression of neural differentiation markers (i.e., Tuj1 and MAP2) of hMSCs compared to tissue culture plate controls. Subcutaneous implantation of the hydrogels for eight weeks induces mild inflammatory reactions. These soft and conductive hydrogels will serve as a useful platform to study the effects of electrical and mechanical signals on stem cells and/or neural cells and to develop multifunctional neural tissue engineering scaffolds. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Collagen-coated polylactic-glycolic acid (PLGA) seeded with neural-differentiated human mesenchymal stem cells as a potential nerve conduit.

    Science.gov (United States)

    Sulong, Ahmad Fadzli; Hassan, Nur Hidayah; Hwei, Ng Min; Lokanathan, Yogeswaran; Naicker, Amaramalar Selvi; Abdullah, Shalimar; Yusof, Mohd Reusmaazran; Htwe, Ohnmar; Idrus, Ruszymah Bt Hj; Haflah, Nor Hazla Mohamed

    2014-01-01

    Autologous nerve grafts to bridge nerve gaps pose various drawbacks. Nerve tissue engineering to promote nerve regeneration using artificial neural conduits has emerged as a promising alternative. To develop an artificial nerve conduit using collagen-coated polylactic-glycolic acid (PLGA) and to analyse the survivability and propagating ability of the neuro-differentiated human mesenchymal stem cells in this conduit. The PLGA conduit was constructed by dip-molding method and coated with collagen by immersing the conduit in collagen bath. The ultra structure of the conduits were examined before they were seeded with neural-differentiated human mesenchymal stem cells (nMSC) and implanted sub-muscularly on nude mice thighs. The non-collagen-coated PLGA conduit seeded with nMSC and non-seeded non-collagen-coated PLGA conduit were also implanted for comparison purposes. The survivability and propagation ability of nMSC was studied by histological and immunohistochemical analysis. The collagen-coated conduits had a smooth inner wall and a highly porous outer wall. Conduits coated with collagen and seeded with nMSCs produced the most number of cells after 3 weeks. The best conduit based on the number of cells contained within it after 3 weeks was the collagen-coated PLGA conduit seeded with neuro-transdifferentiated cells. The collagen-coated PLGA conduit found to be suitable for attachment, survival and proliferation of the nMSC. Minimal cell infiltration was found in the implanted conduits where nearly all of the cells found in the cell seeded conduits are non-mouse origin and have neural cell markers, which exhibit the biocompatibility of the conduits. The collagen-coated PLGA conduit is biocompatible, non-cytotoxic and suitable for use as artificial nerve conduits.

  13. Deletion of a conserved regulatory element required for Hmx1 expression in craniofacial mesenchyme in the dumbo rat: a newly identified cause of congenital ear malformation

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    Lely A. Quina

    2012-11-01

    Hmx1 is a homeodomain transcription factor expressed in the developing eye, peripheral ganglia, and branchial arches of avian and mammalian embryos. Recent studies have identified a loss-of-function allele at the HMX1 locus as the causative mutation in the oculo-auricular syndrome (OAS in humans, characterized by ear and eye malformations. The mouse dumbo (dmbo mutation, with similar effects on ear and eye development, also results from a loss-of-function mutation in the Hmx1 gene. A recessive dmbo mutation causing ear malformation in rats has been mapped to the chromosomal region containing the Hmx1 gene, but the nature of the causative allele is unknown. Here we show that dumbo rats and mice exhibit similar neonatal ear and eye phenotypes. In midgestation embryos, dumbo rats show a specific loss of Hmx1 expression in neural-crest-derived craniofacial mesenchyme (CM, whereas Hmx1 is expressed normally in retinal progenitors, sensory ganglia and in CM, which is derived from mesoderm. High-throughput resequencing of 1 Mb of rat chromosome 14 from dmbo/dmbo rats, encompassing the Hmx1 locus, reveals numerous divergences from the rat genomic reference sequence, but no coding changes in Hmx1. Fine genetic mapping narrows the dmbo critical region to an interval of ∼410 kb immediately downstream of the Hmx1 transcription unit. Further sequence analysis of this region reveals a 5777-bp deletion located ∼80 kb downstream in dmbo/dmbo rats that is not apparent in 137 other rat strains. The dmbo deletion region contains a highly conserved domain of ∼500 bp, which is a candidate distal enhancer and which exhibits a similar relationship to Hmx genes in all vertebrate species for which data are available. We conclude that the rat dumbo phenotype is likely to result from loss of function of an ultraconserved enhancer specifically regulating Hmx1 expression in neural-crest-derived CM. Dysregulation of Hmx1 expression is thus a candidate mechanism for congenital ear

  14. Sound Waves Induce Neural Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells via Ryanodine Receptor-Induced Calcium Release and Pyk2 Activation.

    Science.gov (United States)

    Choi, Yura; Park, Jeong-Eun; Jeong, Jong Seob; Park, Jung-Keug; Kim, Jongpil; Jeon, Songhee

    2016-10-01

    Mesenchymal stem cells (MSCs) have shown considerable promise as an adaptable cell source for use in tissue engineering and other therapeutic applications. The aims of this study were to develop methods to test the hypothesis that human MSCs could be differentiated using sound wave stimulation alone and to find the underlying mechanism. Human bone marrow (hBM)-MSCs were stimulated with sound waves (1 kHz, 81 dB) for 7 days and the expression of neural markers were analyzed. Sound waves induced neural differentiation of hBM-MSC at 1 kHz and 81 dB but not at 1 kHz and 100 dB. To determine the signaling pathways involved in the neural differentiation of hBM-MSCs by sound wave stimulation, we examined the Pyk2 and CREB phosphorylation. Sound wave induced an increase in the phosphorylation of Pyk2 and CREB at 45 min and 90 min, respectively, in hBM-MSCs. To find out the upstream activator of Pyk2, we examined the intracellular calcium source that was released by sound wave stimulation. When we used ryanodine as a ryanodine receptor antagonist, sound wave-induced calcium release was suppressed. Moreover, pre-treatment with a Pyk2 inhibitor, PF431396, prevented the phosphorylation of Pyk2 and suppressed sound wave-induced neural differentiation in hBM-MSCs. These results suggest that specific sound wave stimulation could be used as a neural differentiation inducer of hBM-MSCs.

  15. Cadherin-6B stimulates an epithelial mesenchymal transition and the delamination of cells from the neural ectoderm via LIMK/cofilin mediated non-canonical BMP receptor signaling

    Science.gov (United States)

    Park, Ki-Sook; Gumbiner, Barry M.

    2012-01-01

    We previously provided evidence that cadherin-6B induces de-epithelialization of the neural crest prior to delamination and is required for the overall epithelial mesenchymal transition (EMT). Furthermore, de-epithelialization induced by cadherin-6B was found to be mediated by BMP receptor signaling independent of BMP. We now find that de-epithelialization is mediated by non-canonical BMP signaling through the BMP type II receptor (BMPRII) and not by canonical Smad dependent signaling through BMP Type I receptor. The LIM kinase/cofilin pathway mediates non-canonical BMPRII induced de-epithelialization, in response to either cadherin-6B or BMP. LIMK1 induces de-epithelialization in the neural tube and dominant negative LIMK1 decreases de-epithelialization induced by either cadherin-6B or BMP. Cofilin is the major known LIMK1 target and a S3A phosphorylation deficient mutated cofilin inhibits de-epithelialization induced by cadherin-6B as well as LIMK1. Importantly, LIMK1 as well as cadherin-6B can trigger ectopic delamination when co-expressed with the competence factor SOX9, showing that this cadherin-6B stimulated signaling pathway can mediate the full EMT in the appropriate context. These findings suggest that the de-epithelialization step of the neural crest EMT by cadherin-6B/BMPRII involves regulation of actin dynamics via LIMK/cofilin. PMID:22537493

  16. Donor mesenchymal stem cell-derived neural-like cells transdifferentiate into myelin-forming cells and promote axon regeneration in rat spinal cord transection.

    Science.gov (United States)

    Qiu, Xue-Cheng; Jin, Hui; Zhang, Rong-Yi; Ding, Ying; Zeng, Xiang; Lai, Bi-Qin; Ling, Eng-Ang; Wu, Jin-Lang; Zeng, Yuan-Shan

    2015-05-27

    Severe spinal cord injury often causes temporary or permanent damages in strength, sensation, or autonomic functions below the site of the injury. So far, there is still no effective treatment for spinal cord injury. Mesenchymal stem cells (MSCs) have been used to repair injured spinal cord as an effective strategy. However, the low neural differentiation frequency of MSCs has limited its application. The present study attempted to explore whether the grafted MSC-derived neural-like cells in a gelatin sponge (GS) scaffold could maintain neural features or transdifferentiate into myelin-forming cells in the transected spinal cord. We constructed an engineered tissue by co-seeding of MSCs with genetically enhanced expression of neurotrophin-3 (NT-3) and its high-affinity receptor tropomyosin receptor kinase C (TrkC) separately into a three-dimensional GS scaffold to promote the MSCs differentiating into neural-like cells and transplanted it into the gap of a completely transected rat spinal cord. The rats received extensive post-operation care, including cyclosporin A administrated once daily for 2 months. MSCs modified genetically could differentiate into neural-like cells in the MN + MT (NT-3-MSCs + TrKC-MSCs) group 14 days after culture in the GS scaffold. However, after the MSC-derived neural-like cells were transplanted into the injury site of spinal cord, some of them appeared to lose the neural phenotypes and instead transdifferentiated into myelin-forming cells at 8 weeks. In the latter, the MSC-derived myelin-forming cells established myelin sheaths associated with the host regenerating axons. And the injured host neurons were rescued, and axon regeneration was induced by grafted MSCs modified genetically. In addition, the cortical motor evoked potential and hindlimb locomotion were significantly ameliorated in the rat spinal cord transected in the MN + MT group compared with the GS and MSC groups. Grafted MSC-derived neural-like cells in the

  17. Neural Crest Cells Isolated from the Bone Marrow of Transgenic Mice Express JCV T-Antigen.

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    Jennifer Gordon

    Full Text Available JC virus (JCV, a common human polyomavirus, is the etiological agent of the demyelinating disease, progressive multifocal leukoencephalopathy (PML. In addition to its role in PML, studies have demonstrated the transforming ability of the JCV early protein, T-antigen, and its association with some human cancers. JCV infection occurs in childhood and latent virus is thought to be maintained within the bone marrow, which harbors cells of hematopoietic and non-hematopoietic lineages. Here we show that non-hematopoietic mesenchymal stem cells (MSCs isolated from the bone marrow of JCV T-antigen transgenic mice give rise to JCV T-antigen positive cells when cultured under neural conditions. JCV T-antigen positive cells exhibited neural crest characteristics and demonstrated p75, SOX-10 and nestin positivity. When cultured in conditions typical for mesenchymal cells, a population of T-antigen negative cells, which did not express neural crest markers arose from the MSCs. JCV T-antigen positive cells could be cultured long-term while maintaining their neural crest characteristics. When these cells were induced to differentiate into neural crest derivatives, JCV T-antigen was downregulated in cells differentiating into bone and maintained in glial cells expressing GFAP and S100. We conclude that JCV T-antigen can be stably expressed within a fraction of bone marrow cells differentiating along the neural crest/glial lineage when cultured in vitro. These findings identify a cell population within the bone marrow permissible for JCV early gene expression suggesting the possibility that these cells could support persistent viral infection and thus provide clues toward understanding the role of the bone marrow in JCV latency and reactivation. Further, our data provides an excellent experimental model system for studying the cell-type specificity of JCV T-antigen expression, the role of bone marrow-derived stem cells in the pathogenesis of JCV-related diseases

  18. CHARGEd with neural crest defects.

    Science.gov (United States)

    Pauli, Silke; Bajpai, Ruchi; Borchers, Annette

    2017-10-30

    Neural crest cells are highly migratory pluripotent cells that give rise to diverse derivatives including cartilage, bone, smooth muscle, pigment, and endocrine cells as well as neurons and glia. Abnormalities in neural crest-derived tissues contribute to the etiology of CHARGE syndrome, a complex malformation disorder that encompasses clinical symptoms like coloboma, heart defects, atresia of the choanae, retarded growth and development, genital hypoplasia, ear anomalies, and deafness. Mutations in the chromodomain helicase DNA-binding protein 7 (CHD7) gene are causative of CHARGE syndrome and loss-of-function data in different model systems have firmly established a role of CHD7 in neural crest development. Here, we will summarize our current understanding of the function of CHD7 in neural crest development and discuss possible links of CHARGE syndrome to other developmental disorders. © 2017 Wiley Periodicals, Inc.

  19. Neural crest contributions to the lamprey head

    Science.gov (United States)

    McCauley, David W.; Bronner-Fraser, Marianne

    2003-01-01

    The neural crest is a vertebrate-specific cell population that contributes to the facial skeleton and other derivatives. We have performed focal DiI injection into the cranial neural tube of the developing lamprey in order to follow the migratory pathways of discrete groups of cells from origin to destination and to compare neural crest migratory pathways in a basal vertebrate to those of gnathostomes. The results show that the general pathways of cranial neural crest migration are conserved throughout the vertebrates, with cells migrating in streams analogous to the mandibular and hyoid streams. Caudal branchial neural crest cells migrate ventrally as a sheet of cells from the hindbrain and super-pharyngeal region of the neural tube and form a cylinder surrounding a core of mesoderm in each pharyngeal arch, similar to that seen in zebrafish and axolotl. In addition to these similarities, we also uncovered important differences. Migration into the presumptive caudal branchial arches of the lamprey involves both rostral and caudal movements of neural crest cells that have not been described in gnathostomes, suggesting that barriers that constrain rostrocaudal movement of cranial neural crest cells may have arisen after the agnathan/gnathostome split. Accordingly, neural crest cells from a single axial level contributed to multiple arches and there was extensive mixing between populations. There was no apparent filling of neural crest derivatives in a ventral-to-dorsal order, as has been observed in higher vertebrates, nor did we find evidence of a neural crest contribution to cranial sensory ganglia. These results suggest that migratory constraints and additional neural crest derivatives arose later in gnathostome evolution.

  20. Translocation of latex beads after laser ablation of the avian neural crest.

    Science.gov (United States)

    Coulombe, J N; Bronner-Fraser, M

    1984-11-01

    Previous studies from this laboratory (M.E. Bronner-Fraser, 1982, Dev. Biol. 91, 50-63) have demonstrated that latex beads translocate ventrally after injection into avian embryos during the phase of neural crest migration, to settle in the vicinity of neural-crest-derived structures. In order to examine the role of host neural crest cells in the ventral translocation of implanted beads, latex beads have been injected into regions of embryos from which the neural crest cells have been ablated using a laser microbeam. Prior to their migratory phase, neural crest cells reside in the dorsal portion of the neural tube. Laser irradiation of the dorsal neural tube was used to reproducibly achieve either partial or complete ablation of neural crest cells from the irradiated regions. The effectiveness of the ablation was assessed by the degree of reduction in dorsal root ganglia, a neural crest derivative. Because of the rapidity and precision of this technique, it was possible to selectively remove neural crest cells without significantly altering other embryonic structures. The results indicate that, after injection of latex beads into the somites of embryos whose neural crest cells were removed by laser irradiation, the beads translocate ventrally in the absence of the endogenous neural crest.

  1. DNA methyltransferase 3b is dispensable for mouse neural crest development.

    Directory of Open Access Journals (Sweden)

    Bridget T Jacques-Fricke

    Full Text Available The neural crest is a population of multipotent cells that migrates extensively throughout vertebrate embryos to form diverse structures. Mice mutant for the de novo DNA methyltransferase DNMT3b exhibit defects in two neural crest derivatives, the craniofacial skeleton and cardiac ventricular septum, suggesting that DNMT3b activity is necessary for neural crest development. Nevertheless, the requirement for DNMT3b specifically in neural crest cells, as opposed to interacting cell types, has not been determined. Using a conditional DNMT3b allele crossed to the neural crest cre drivers Wnt1-cre and Sox10-cre, neural crest DNMT3b mutants were generated. In both neural crest-specific and fully DNMT3b-mutant embryos, cranial neural crest cells exhibited only subtle migration defects, with increased numbers of dispersed cells trailing organized streams in the head. In spite of this, the resulting cranial ganglia, craniofacial skeleton, and heart developed normally when neural crest cells lacked DNMT3b. This indicates that DNTM3b is not necessary in cranial neural crest cells for their development. We conclude that defects in neural crest derivatives in DNMT3b mutant mice reflect a requirement for DNMT3b in lineages such as the branchial arch mesendoderm or the cardiac mesoderm that interact with neural crest cells during formation of these structures.

  2. Mesenchymal stem cells promote augmented response of endogenous neural stem cells in spinal cord injury of rats

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    Marta Rocha Araujo

    2016-06-01

    Full Text Available Traumatic spinal cord injury results in severe neurological deficits, mostly irreversible. The cell therapy represents a strategy for treatment particularly with the use of stem cells with satisfactory results in several experimental models. The aim of the study was to compare the treatment of spinal cord injury (SCI with and without mesenchymal stem cells (MSC, to investigate whether MSCs migrate and/or remain at the site of injury, and to analyze the effects of MSCs on inflammation, astrocytic reactivity and activation of endogenous stem cells. Three hours after SCI, animals received bone marrow-derived MSCs (1×107 in 1mL PBS, IV. Animals were euthanized 24 hours, 7 and 21 days post-injury. The MSC were not present in the site of the lesion and the immunofluorescent evaluation showed significant attenuation of inflammatory response with reduction in macrophages labeled with anti-CD68 antibody (ED1, decreased immunoreactivity of astrocytes (GFAP+ and greater activation of endogenous stem cells (nestin+ in the treated groups. Therefore, cell transplantation have a positive effect on recovery from traumatic spinal cord injury possibly due to the potential of MSCs to attenuate the immune response.

  3. Transplants of adult mesenchymal and neural stem cells provide neuroprotection and behavioral sparing in a transgenic rat model of Huntington's disease.

    Science.gov (United States)

    Rossignol, Julien; Fink, Kyle; Davis, Kendra; Clerc, Steven; Crane, Andrew; Matchynski, Jessica; Lowrance, Steven; Bombard, Matthew; Dekorver, Nicholas; Lescaudron, Laurent; Dunbar, Gary L

    2014-02-01

    Stem cells have gained significant interest as a potential treatment of neurodegenerative diseases, including Huntington's disease (HD). One source of these cells is adult neural stem cells (aNSCs), which differentiate easily into neuronal lineages. However, these cells are vulnerable to immune responses following transplantation. Another source is bone-marrow-derived mesenchymal stem cells (MSCs), which release neurotrophic factors and anti-inflammatory cytokines following transplantation, and are less vulnerable to rejection. The goal of this study was to compare the efficacy of transplants of MSCs, aNSCs, or cotransplants of MSCs and aNSCs for reducing deficits in a transgenic rat model of HD. HD rats received intrastriatal transplantations of 400,000 MSCs, aNSCs, or a combination of MSCs/aNSCs, while wild-type and HD controls were given vehicle. Rats were tested on the rotarod over the course of 20 weeks. The results indicated that transplants of: (a) aNSCs produced a strong immune response and conferred short-term behavioral benefits; (b) MSCs elicited a relatively weak immune response, and provided a longer term behavioral benefit; and (c) combined MSCs and aNSCs conferred long-term behavioral benefits and increased survival of the transplanted aNSCs. The finding that cotransplanting MSCs with aNSCs can prolong aNSC survival and provide greater behavioral sparing than when the transplants contains only aNSCs suggests that MSCs are capable of creating a more suitable microenvironment for aNSC survival. This cotransplantation strategy may be useful as a future therapeutic option for treating HD, especially if long-term survival of differentiated cells proves to be critically important for preserving lasting functional outcomes. Copyright © 2013 AlphaMed Press.

  4. Neural progenitors generated from the mesenchymal stem cells of first-trimester human placenta matured in the hypoxic-ischemic rat brain and mediated restoration of locomotor activity.

    Science.gov (United States)

    Park, S; Koh, S-E; Maeng, S; Lee, W-D; Lim, J; Lee, Y-J

    2011-03-01

    Term placenta is a great reservoir of mesenchymal stem cells (MSCs), however, the potential of the earlier placenta is largely unknown. In this report, we established 17 MSC lines from 19 first-trimester human placenta (fPMSC). fPMSC proliferated for 90-150 days in vitro and by enhanced cellular interaction, fPMSC differentiated into nestin-expressing neural progenitor cells (fPMSC-NP), accompanied by inductions of immature neuron-specific genes. Therapeutic effect of the fPMSC-NP was tested in the animal model of hypoxia-ischemia (HI) which was devastating to dopaminergic neurons and to locomotor activity. Improvement of motor activity was evident as early as 2 weeks after transplantation of the fPMSC-NP into bilateral striatum and became indistinguishable from that of the age-matched normal animals by 8 weeks but no spontaneous recovery was observed in the control-grafted animals. Immunohistochemical analyses revealed that the implanted fPMSC-NP matured into ectodermal cells including the tyrosine hydroxylase (TH)-expressing neurons in the recipient striatum. So, the improved motor behavior was likely due to the dopaminergic differentiation of the implanted fPMSC-NP in the dopaminergic-denervated host brain. Based on this result, we propose that progenitors may be more advantageous than the terminally differentiated cells for the purpose of cell replacement therapies since the progenitors are easily obtainable and are expected to be more pliable to the new environment. Copyright © 2011. Published by Elsevier Ltd.

  5. Derivation of mesenchymal stromal cells from pluripotent stem cells through a neural crest lineage using small molecule compounds with defined media.

    Directory of Open Access Journals (Sweden)

    Makoto Fukuta

    Full Text Available Neural crest cells (NCCs are an embryonic migratory cell population with the ability to differentiate into a wide variety of cell types that contribute to the craniofacial skeleton, cornea, peripheral nervous system, and skin pigmentation. This ability suggests the promising role of NCCs as a source for cell-based therapy. Although several methods have been used to induce human NCCs (hNCCs from human pluripotent stem cells (hPSCs, such as embryonic stem cells (ESCs and induced pluripotent stem cells (iPSCs, further modifications are required to improve the robustness, efficacy, and simplicity of these methods. Chemically defined medium (CDM was used as the basal medium in the induction and maintenance steps. By optimizing the culture conditions, the combination of the GSK3β inhibitor and TGFβ inhibitor with a minimum growth factor (insulin very efficiently induced hNCCs (70-80% from hPSCs. The induced hNCCs expressed cranial NCC-related genes and stably proliferated in CDM supplemented with EGF and FGF2 up to at least 10 passages without changes being observed in the major gene expression profiles. Differentiation properties were confirmed for peripheral neurons, glia, melanocytes, and corneal endothelial cells. In addition, cells with differentiation characteristics similar to multipotent mesenchymal stromal cells (MSCs were induced from hNCCs using CDM specific for human MSCs. Our simple and robust induction protocol using small molecule compounds with defined media enabled the generation of hNCCs as an intermediate material producing terminally differentiated cells for cell-based innovative medicine.

  6. Polyurethane/polylactide-based biomaterials combined with rat olfactory bulb-derived glial cells and adipose-derived mesenchymal stromal cells for neural regenerative medicine applications

    Energy Technology Data Exchange (ETDEWEB)

    Grzesiak, Jakub, E-mail: grzesiak.kuba@gmail.com [Electron Microscopy Laboratory, University of Environmental and Life Sciences, Kozuchowska 5b, 51-631 Wroclaw (Poland); Marycz, Krzysztof [Electron Microscopy Laboratory, University of Environmental and Life Sciences, Kozuchowska 5b, 51-631 Wroclaw (Poland); Szarek, Dariusz [Department of Neurosurgery, Lower Silesia Specialist Hospital of T. Marciniak, Emergency Medicine Center, Traugutta 116, 50-420 Wroclaw (Poland); Bednarz, Paulina [State Higher Vocational School in Tarnów, Mickiewicza 8, 33-100 Tarnów (Poland); Laska, Jadwiga [AGH University of Science and Technology, Faculty of Materials Science and Ceramics, Mickiewicza 30, 30-059 Kraków (Poland)

    2015-07-01

    Research concerning the elaboration and application of biomaterial which may support the nerve tissue regeneration is currently one of the most promising directions. Biocompatible polymer devices are noteworthy group among the numerous types of potentially attractive biomaterials for regenerative medicine application. Polylactides and polyurethanes may be utilized for developing devices for supporting the nerve regeneration, like nerve guide conduits or bridges connecting the endings of broken nerve tracts. Moreover, the combination of these biomaterial devices with regenerative cell populations, like stem or precursor cells should significantly improve the final therapeutic effect. Therefore, the composition and structure of final device should support the proper adhesion and growth of cells destined for clinical application. In current research, the three polymer mats elaborated for connecting the broken nerve tracts, made from polylactide, polyurethane and their blend were evaluated both for physical properties and in vitro, using the olfactory-bulb glial cells and mesenchymal stem cells. The evaluation of Young's modulus, wettability and roughness of obtained materials showed the differences between analyzed samples. The analysis of cell adhesion, proliferation and morphology showed that the polyurethane–polylactide blend was the most neutral for cells in culture, while in the pure polymer samples there were significant alterations observed. Our results indicated that polyurethane–polylactide blend is an optimal composition for culturing and delivery of glial and mesenchymal stem cells. - Highlights: • Polyurethane–polylactide blends exhibit different characteristics from pure polymers. • Pure PU and PLA negatively influence on morphology of glial and mesenchymal cells. • PU/PLA blend was neutral for glial and mesenchymal cell proliferation and morphology.

  7. Cardiovascular Development and the Colonizing Cardiac Neural Crest Lineage

    Directory of Open Access Journals (Sweden)

    Paige Snider

    2007-01-01

    Full Text Available Although it is well established that transgenic manipulation of mammalian neural crest-related gene expression and microsurgical removal of premigratory chicken and Xenopus embryonic cardiac neural crest progenitors results in a wide spectrum of both structural and functional congenital heart defects, the actual functional mechanism of the cardiac neural crest cells within the heart is poorly understood. Neural crest cell migration and appropriate colonization of the pharyngeal arches and outflow tract septum is thought to be highly dependent on genes that regulate cell-autonomous polarized movement (i.e., gap junctions, cadherins, and noncanonical Wnt1 pathway regulators. Once the migratory cardiac neural crest subpopulation finally reaches the heart, they have traditionally been thought to participate in septation of the common outflow tract into separate aortic and pulmonary arteries. However, several studies have suggested these colonizing neural crest cells may also play additional unexpected roles during cardiovascular development and may even contribute to a crest-derived stem cell population. Studies in both mice and chick suggest they can also enter the heart from the venous inflow as well as the usual arterial outflow region, and may contribute to the adult semilunar and atrioventricular valves as well as part of the cardiac conduction system. Furthermore, although they are not usually thought to give rise to the cardiomyocyte lineage, neural crest cells in the zebrafish (Danio rerio can contribute to the myocardium and may have different functions in a species-dependent context. Intriguingly, both ablation of chick and Xenopus premigratory neural crest cells, and a transgenic deletion of mouse neural crest cell migration or disruption of the normal mammalian neural crest gene expression profiles, disrupts ventral myocardial function and/or cardiomyocyte proliferation. Combined, this suggests that either the cardiac neural crest

  8. Polyurethane/polylactide-based biomaterials combined with rat olfactory bulb-derived glial cells and adipose-derived mesenchymal stromal cells for neural regenerative medicine applications.

    Science.gov (United States)

    Grzesiak, Jakub; Marycz, Krzysztof; Szarek, Dariusz; Bednarz, Paulina; Laska, Jadwiga

    2015-01-01

    Research concerning the elaboration and application of biomaterial which may support the nerve tissue regeneration is currently one of the most promising directions. Biocompatible polymer devices are noteworthy group among the numerous types of potentially attractive biomaterials for regenerative medicine application. Polylactides and polyurethanes may be utilized for developing devices for supporting the nerve regeneration, like nerve guide conduits or bridges connecting the endings of broken nerve tracts. Moreover, the combination of these biomaterial devices with regenerative cell populations, like stem or precursor cells should significantly improve the final therapeutic effect. Therefore, the composition and structure of final device should support the proper adhesion and growth of cells destined for clinical application. In current research, the three polymer mats elaborated for connecting the broken nerve tracts, made from polylactide, polyurethane and their blend were evaluated both for physical properties and in vitro, using the olfactory-bulb glial cells and mesenchymal stem cells. The evaluation of Young's modulus, wettability and roughness of obtained materials showed the differences between analyzed samples. The analysis of cell adhesion, proliferation and morphology showed that the polyurethane-polylactide blend was the most neutral for cells in culture, while in the pure polymer samples there were significant alterations observed. Our results indicated that polyurethane-polylactide blend is an optimal composition for culturing and delivery of glial and mesenchymal stem cells. Copyright © 2015. Published by Elsevier B.V.

  9. The Extracellular Environment's Effect on Cellular Processes: An In Vitro Study of Mechanical and Chemical Cues on Human Mesenchymal Stem Cells and C17.2 Neural Stem Cells

    Science.gov (United States)

    Casey, Meghan E.

    Stem cells are widely used in the area of tissue engineering. The ability of cells to interact with materials on the nano- and micro- level is important in the success of the biomaterial. It is well-known that cells respond to their micro- and nano-environments through a process termed chemo-mechanotransduction. It is important to establish standard protocols for cellular experiments, as chemical modifications to maintenance environments can alter long-term research results. In this work, the effects of different media compositions on human mesenchymal stem cells (hMSCs) throughout normal in vitro maintenance are investigated. Changes in RNA regulation, protein expression and proliferation are studied via quantitative polymerase chain reaction (qPCR), immunocytochemistry (ICC) and cell counts, respectively. Morphological differences are also observed throughout the experiment. Results of this study illustrate the dynamic response of hMSC maintenance to differences in growth medium and passage number. These experiments highlight the effect growth medium has on in vitro experiments and the need of consistent protocols in hMSC research. A substantial opportunity exists in neuronal research to develop a material platform that allows for both the proliferation and differentiation of stem cells into neurons and the ability to quantify the secretome of neuronal cells. Anodic aluminum oxide (AAO) membranes are fabricated in a two-step anodization procedure where voltage is varied to control the pore size and morphology of the membranes. C17.2 neural stem cells are differentiated on the membranes via serum-withdrawal. Cellular growth is characterized by scanning electron microscopy (SEM), ICC and qPCR. ImageJ software is used to obtain phenotypic cell counts and neurite outgrowth lengths. Results indicate a highly tunable correlation between AAO nanopore sizes and differentiated cell populations. By selecting AAO membranes with specific pore size ranges, control of neuronal

  10. Pax7 lineage contributions to the mammalian neural crest.

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    Barbara Murdoch

    Full Text Available Neural crest cells are vertebrate-specific multipotent cells that contribute to a variety of tissues including the peripheral nervous system, melanocytes, and craniofacial bones and cartilage. Abnormal development of the neural crest is associated with several human maladies including cleft/lip palate, aggressive cancers such as melanoma and neuroblastoma, and rare syndromes, like Waardenburg syndrome, a complex disorder involving hearing loss and pigment defects. We previously identified the transcription factor Pax7 as an early marker, and required component for neural crest development in chick embryos. In mammals, Pax7 is also thought to play a role in neural crest development, yet the precise contribution of Pax7 progenitors to the neural crest lineage has not been determined.Here we use Cre/loxP technology in double transgenic mice to fate map the Pax7 lineage in neural crest derivates. We find that Pax7 descendants contribute to multiple tissues including the cranial, cardiac and trunk neural crest, which in the cranial cartilage form a distinct regional pattern. The Pax7 lineage, like the Pax3 lineage, is additionally detected in some non-neural crest tissues, including a subset of the epithelial cells in specific organs.These results demonstrate a previously unappreciated widespread distribution of Pax7 descendants within and beyond the neural crest. They shed light regarding the regionally distinct phenotypes observed in Pax3 and Pax7 mutants, and provide a unique perspective into the potential roles of Pax7 during disease and development.

  11. Neural Crest Stem Cells from Dental Tissues: A New Hope for Dental and Neural Regeneration

    Directory of Open Access Journals (Sweden)

    Gaskon Ibarretxe

    2012-01-01

    Full Text Available Several stem cell sources persist in the adult human body, which opens the doors to both allogeneic and autologous cell therapies. Tooth tissues have proven to be a surprisingly rich and accessible source of neural crest-derived ectomesenchymal stem cells (EMSCs, which may be employed to repair disease-affected oral tissues in advanced regenerative dentistry. Additionally, one area of medicine that demands intensive research on new sources of stem cells is nervous system regeneration, since this constitutes a therapeutic hope for patients affected by highly invalidating conditions such as spinal cord injury, stroke, or neurodegenerative diseases. However, endogenous adult sources of neural stem cells present major drawbacks, such as their scarcity and complicated obtention. In this context, EMSCs from dental tissues emerge as good alternative candidates, since they are preserved in adult human individuals, and retain both high proliferation ability and a neural-like phenotype in vitro. In this paper, we discuss some important aspects of tissue regeneration by cell therapy and point out some advantages that EMSCs provide for dental and neural regeneration. We will finally review some of the latest research featuring experimental approaches and benefits of dental stem cell therapy.

  12. Boundary cap neural crest stem cells homotopically implanted to the injured dorsal root transitional zone give rise to different types of neurons and glia in adult rodents

    OpenAIRE

    Trolle, Carl; Abrahamsson, Ninnie; König, Niclas; Vasylovska, Svitlana; Kozlova, Elena

    2014-01-01

    The boundary cap is a transient group of neural crest-derived cells located at the presumptive dorsal root transitional zone (DRTZ) when sensory axons enter the spinal cord during development. Later, these cells migrate to dorsal root ganglia and differentiate into subtypes of sensory neurons and glia. After birth when the DRTZ is established, sensory axons are no longer able to enter the spinal cord. Here we explored the fate of mouse bNCSCs implanted to the uninjured DRTZ after dorsal root ...

  13. Embryonic requirements for ErbB signaling in neural crest development and adult pigment pattern formation

    Science.gov (United States)

    Budi, Erine H.; Patterson, Larissa B.; Parichy, David M.

    2009-01-01

    SUMMARY Vertebrate pigment cells are derived from neural crest cells and are a useful system for studying neural crest-derived traits during post-embryonic development. In zebrafish, neural crest-derived melanophores differentiate during embryogenesis to produce stripes in the early larva. Dramatic changes to the pigment pattern occur subsequently during the larva-to-adult transformation, or metamorphosis. At this time, embryonic melanophores are replaced by newly differentiating metamorphic melanophores that form the adult stripes. Mutants with normal embryonic/early larval pigment patterns but defective adult patterns identify factors required uniquely to establish, maintain, or recruit the latent precursors to metamorphic melanophores. We show that one such mutant, picasso, lacks most metamorphic melanophores and results from mutations in the ErbB gene erbb3b, encoding an EGFR-like receptor tyrosine kinase. To identify critical periods for ErbB activities, we treated fish with pharmacological ErbB inhibitors and also knocked-down erbb3b by morpholino injection. These analyses reveal an embryonic critical period for ErbB signaling in promoting later pigment pattern metamorphosis, despite the normal patterning of embryonic/early larval melanophores. We further demonstrate a peak requirement during neural crest migration that correlates with early defects in neural crest pathfinding and peripheral ganglion formation. Finally, we show that erbb3b activities are both autonomous and non-autonomous to the metamorphic melanophore lineage. These data identify a very early, embryonic, requirement for erbb3b in the development of much later metamorphic melanophores, and suggest complex modes by which ErbB signals promote adult pigment pattern development. PMID:18508863

  14. Células mesenquimales de médula ósea: Diferenciación y potencial reemplazo neuronal Mesenchymal stem cells: Differentiation and alternative source of neural tissue

    Directory of Open Access Journals (Sweden)

    Catalina C. Bianchi de Di Risio

    2004-12-01

    Full Text Available Las células troncales embrionarias son totipotentes y se encuentran en pequeño número en el blastocisto donde pueden expandirse en forma indiferenciada durante un corto tiempo y de acuerdo al sitio donde se alojan, ellas adquirirán determinados fenotipos de diferenciación. Las células hemopoyéticas troncales se caracterizan por poseer un gran potencial proliferativo, cuyo modelo de regulación es jerárquico. Ellas retienen, a lo largo de su existencia, un cierto grado de plasticidad, lo cual hace que se puedan diferenciar en distintos tipos de células o de tejidos no hemopoyéticos, de acuerdo al microambiente donde se encuentran o bien a la presencia de ciertos factores estimulantes. En trabajos recientes se han podido aislar, por adherencia al plástico, en cultivo in vitro de médula ósea, células no hemopoyéticas que fueron llamadas mesenquimales por su semejanza con el tejido mesenquimal del embrión. Estas células, in vitro, pueden ser inducidas hacia nuevas líneas celulares, que se diferenciarán en nuevos tejidos. Las expectativas del beneficio terapéutico del transplante de médula ósea como el de células mesenquimales en enfermedades no hemopoyéticas son grandes, porque al utilizar tejidos o células autólogas, se evitan los graves problemas del rechazo inmunológico. En el caso del tejido nervioso la problemática de una fuente adecuada de donantes hace el tema especialmente interesante.Embryonic stem cells are a population of cells located in the blastocyst, commited to specific differentiation according to spatial and temporal factors such as age and place of final location. Despite the final fate of hematic cells, hemopoietic cells retain a relative degree of plasticity dependent on environmental factors. Mesenchymal cells are a well differentiated population of bone marrow derived non hemopoietic cells with totipotential properties. The medical interest of such totipotentiality rests in the potential of such

  15. Secondary Release of Exosomes From Astrocytes Contributes to the Increase in Neural Plasticity and Improvement of Functional Recovery After Stroke in Rats Treated With Exosomes Harvested From MicroRNA 133b-Overexpressing Multipotent Mesenchymal Stromal Cells.

    Science.gov (United States)

    Xin, Hongqi; Wang, Fengjie; Li, Yanfeng; Lu, Qing-E; Cheung, Wing Lee; Zhang, Yi; Zhang, Zheng Gang; Chopp, Michael

    2017-02-16

    We previously demonstrated that multipotent mesenchymal stromal cells (MSCs) that overexpress microRNA 133b (miR-133b) significantly improve functional recovery in rats subjected to middle cerebral artery occlusion (MCAO) compared with naive MSCs and that exosomes generated from naive MSCs mediate the therapeutic benefits of MSC therapy for stroke. Here we investigated whether exosomes isolated from miR-133b-overexpressing MSCs (Ex-miR-133b+) exert amplified therapeutic effects. Rats subjected to 2 h of MCAO were intra-arterially injected with Ex-miR-133b+, exosomes from MSCs infected by blank vector (Ex-Con), or phosphate-buffered saline (PBS) and were sacrificed 28 days after MCAO. Compared with the PBS treatment, both exosome treatment groups exhibited significant improvement of functional recovery. Ex-miR-133b+ treatment significantly increased functional improvement and neurite remodeling/brain plasticity in the ischemic boundary area compared with the Ex-Con treatment. Treatment with Ex-miR-133b+ also significantly increased brain exosome content compared with Ex-Con treatment. To elucidate mechanisms underlying the enhanced therapeutic effects of Ex-miR-133b+, astrocytes cultured under oxygen- and glucose-deprived (OGD) conditions were incubated with exosomes harvested from naive MSCs (Ex-Naive), miR-133b downregulated MSCs (Ex-miR-133b-), and Ex-miR-133b+. Compared with the Ex-Naive treatment, Ex-miR-133b+ significantly increased exosomes released by OGD astrocytes, whereas Ex-miR-133b- significantly decreased the release. Also, exosomes harvested from OGD astrocytes treated with Ex-miR-133b+ significantly increased neurite branching and elongation of cultured cortical embryonic rat neurons compared with the exosomes from OGD astrocytes subjected to Ex-Con. Our data suggest that exosomes harvested from miR-133b-overexpressing MSCs improve neural plasticity and functional recovery after stroke with a contribution from a stimulated secondary release of

  16. Early Determination of the Periodontal Domain by the Wnt-Antagonist Frzb/Sfrp3

    OpenAIRE

    Thimios A. Mitsiadis; Pierfrancesco Pagella; Claudio Cantù

    2017-01-01

    Odontogenesis results from the continuous and reciprocal interaction between cells of the oral epithelium and cranial neural crest-derived mesenchyme. The canonical Wnt signaling pathway plays a fundamental role in mediating these interactions from the earliest stages of tooth development. Here we analyze by in situ hybridization the expression patterns of the extracellular Wnt antagonist Frzb/Sfrp3. Although Frzb is expressed in dental mesenchymal cells from the earliest stages of odontogene...

  17. Bone marrow mesenchymal stem cell therapy in ischemic stroke: mechanisms of action and treatment optimization strategies

    Directory of Open Access Journals (Sweden)

    Guihong Li

    2016-01-01

    Full Text Available Animal and clinical studies have confirmed the therapeutic effect of bone marrow mesenchymal stem cells on cerebral ischemia, but their mechanisms of action remain poorly understood. Here, we summarize the transplantation approaches, directional migration, differentiation, replacement, neural circuit reconstruction, angiogenesis, neurotrophic factor secretion, apoptosis, immunomodulation, multiple mechanisms of action, and optimization strategies for bone marrow mesenchymal stem cells in the treatment of ischemic stroke. We also explore the safety of bone marrow mesenchymal stem cell transplantation and conclude that bone marrow mesenchymal stem cell transplantation is an important direction for future treatment of cerebral ischemia. Determining the optimal timing and dose for the transplantation are important directions for future research.

  18. Aebp2 as an epigenetic regulator for neural crest cells.

    Directory of Open Access Journals (Sweden)

    Hana Kim

    Full Text Available Aebp2 is a potential targeting protein for the mammalian Polycomb Repression Complex 2 (PRC2. We generated a mutant mouse line disrupting the transcription of Aebp2 to investigate its in vivo roles. Aebp2-mutant homozygotes were embryonic lethal while heterozygotes survived to adulthood with fertility. In developing mouse embryos, Aebp2 is expressed mainly within cells of neural crest origin. In addition, many heterozygotes display a set of phenotypes, enlarged colon and hypopigmentation, similar to those observed in human patients with Hirschsprung's disease and Waardenburg syndrome. These phenotypes are usually caused by the absence of the neural crest-derived ganglia in hindguts and melanocytes. ChIP analyses demonstrated that the majority of the genes involved in the migration and development process of neural crest cells are downstream target genes of AEBP2 and PRC2. Furthermore, expression analyses confirmed that some of these genes are indeed affected in the Aebp2 heterozygotes. Taken together, these results suggest that Aebp2 may regulate the migration and development of the neural crest cells through the PRC2-mediated epigenetic mechanism.

  19. The in vivo developmental potential of porcine skin-derived progenitors and neural stem cells.

    Science.gov (United States)

    Zhao, Ming-Tao; Yang, Xiaoyu; Lee, Kiho; Mao, Jiude; Teson, Jennifer M; Whitworth, Kristin M; Samuel, Melissa S; Spate, Lee D; Murphy, Clifton N; Prather, Randall S

    2012-09-20

    Multipotent skin-derived progenitors (SKPs) can be traced back to embryonic neural crest cells and are able to differentiate into both neural and mesodermal progeny in vitro. Neural stem cells (NSCs) are capable of self-renewing and can contribute to neuron and glia in the nervous system. Recently, we derived porcine SKPs and NSCs from the same enhanced green fluorescent protein (EGFP) transgenic fetuses and demonstrated that SKPs could contribute to neural and mesodermal lineages in vivo. However, it remains unclear whether porcine SKPs and NSCs can generate ectoderm and mesoderm lineages or other germ layers in vivo. Embryonic chimeras are a well-established tool for investigating cell lineage determination and cell potency through normal embryonic development. Thus, the purpose of this study was to investigate the in vivo developmental potential of porcine SKPs and fetal brain-derived NSCs by chimera production. Porcine SKPs, NSCs, and fibroblasts were injected into precompact in vitro fertilized embryos (IVF) and then transferred into corresponding surrogates 24 h postinjection. We found that porcine SKPs could incorporate into the early embryos and contribute to various somatic tissues of the 3 germ layers in postnatal chimera, and especially have an endodermal potency. However, this developmental potential is compromised when they differentiate into fibroblasts. In addition, porcine NSCs fail to incorporate into host embryos and contribute to chimeric piglets. Therefore, neural crest-derived SKPs may represent a more primitive state than their counterpart neural stem cells in terms of their contributions to multiple cell lineages.

  20. Gene-environment interactions and the enteric nervous system: Neural plasticity and Hirschsprung disease prevention.

    Science.gov (United States)

    Heuckeroth, Robert O; Schäfer, Karl-Herbert

    2016-09-15

    Intestinal function is primarily controlled by an intrinsic nervous system of the bowel called the enteric nervous system (ENS). The cells of the ENS are neural crest derivatives that migrate into and through the bowel during early stages of organogenesis before differentiating into a wide variety of neurons and glia. Although genetic factors critically underlie ENS development, it is now clear that many non-genetic factors may influence the number of enteric neurons, types of enteric neurons, and ratio of neurons to glia. These non-genetic influences include dietary nutrients and medicines that may impact ENS structure and function before or after birth. This review summarizes current data about gene-environment interactions that affect ENS development and suggests that these factors may contribute to human intestinal motility disorders like Hirschsprung disease or irritable bowel syndrome. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Gene-environment interactions and the enteric nervous system: Neural plasticity and Hirschsprung disease prevention

    Science.gov (United States)

    Heuckeroth, Robert O.; Schäfer, Karl-Herbert

    2016-01-01

    Intestinal function is primarily controlled by an intrinsic nervous system of the bowel called the enteric nervous system (ENS). The cells of the ENS are neural crest derivatives that migrate into and through the bowel during early stages of organogenesis before differentiating into a wide variety of neurons and glia. Although genetic factors critically underlie ENS development, it is now clear that many non-genetic factors may influence the number of enteric neurons, types of enteric neurons, and ratio of neurons to glia. These non-genetic influences include dietary nutrients and medicines that may impact ENS structure and function before or after birth. This review summarizes current data about gene-environment interactions that affect ENS development and suggests that these factors may contribute to human intestinal motility disorders like Hirschsprung disease or irritable bowel syndrome. PMID:26997034

  2. Sphere-Derived Multipotent Progenitor Cells Obtained From Human Oral Mucosa Are Enriched in Neural Crest Cells.

    Science.gov (United States)

    Abe, Shigehiro; Yamaguchi, Satoshi; Sato, Yutaka; Harada, Kiyoshi

    2016-01-01

    : Although isolation of oral mucosal stromal stem cells has been previously reported, complex isolation methods are not suitable for clinical application. The neurosphere culture technique is a convenient method for the isolation of neural stem cells and neural crest stem cells (NCSCs); neurosphere generation is a phenotype of NCSCs. However, the molecular details underlying the isolation and characterization of human oral mucosa stromal cells (OMSCs) by neurosphere culture are not understood. The purpose of the present study was to isolate NCSCs from oral mucosa using the neurosphere technique and to establish effective in vivo bone tissue regeneration methods. Human OMSCs were isolated from excised human oral mucosa; these cells formed spheres in neurosphere culture conditions. Oral mucosa sphere-forming cells (OMSFCs) were characterized by biological analyses of stem cells. Additionally, composites of OMSFCs and multiporous polylactic acid scaffolds were implanted subcutaneously into immunocompromised mice. OMSFCs had the capacity for self-renewal and expressed neural crest-related markers (e.g., nestin, CD44, slug, snail, and MSX1). Furthermore, upregulated expression of neural crest-related genes (EDNRA, Hes1, and Sox9) was observed in OMSFCs, which are thought to contain an enriched population of neural crest-derived cells. The expression pattern of α2-integrin (CD49b) in OMSFCs also differed from that in OMSCs. Finally, OMSFCs were capable of differentiating into neural crest lineages in vitro and generating ectopic bone tissues even in the subcutaneous region. The results of the present study suggest that OMSFCs are an ideal source of cells for the neural crest lineage and hard tissue regeneration. The sphere culture technique is a convenient method for isolating stem cells. However, the isolation and characterization of human oral mucosa stromal cells (OMSCs) using the sphere culture system are not fully understood. The present study describes the

  3. Involvement of Neptune in induction of the hatching gland and neural crest in the Xenopus embryo.

    Science.gov (United States)

    Kurauchi, Takayuki; Izutsu, Yumi; Maéno, Mitsugu

    2010-01-01

    Neptune, a Krüppel-like transcription factor, is expressed in various regions of the developing Xenopus embryo and it has multiple functions in the process of development in various organs. In situ hybridization analysis showed that Neptune is expressed in the boundary region between neural and non-neural tissues at the neurula stage, but little is known about the function of Neptune in this region. Here, we examined the expression and function of Neptune in the neural plate border (NPB) in the Xenopus embryo. Depletion of Neptune protein in developing embryos by using antisense MO caused loss of the hatching gland and otic vesicle as well as malformation of neural crest-derived cranial cartilages and melanocytes. Neptune MO also suppressed the expression of hatching gland and neural crest markers such as he, snail2, sox9 and msx1 at the neurula stage. Subsequent experiments showed that Neptune is necessary and sufficient for the differentiation of hatching gland cells and that it is located downstream of pax3 in the signal regulating the differentiation of these cells. Thus, Neptune is a new member of hatching gland specifier and plays a physiological role in determination and specification of multiple lineages derived from the NPB region.

  4. Mesenchymal chondrosarcoma of kidney

    Directory of Open Access Journals (Sweden)

    Ruchita Tyagi

    2014-01-01

    Full Text Available Mesenchymal chondrosarcoma of the kidney is a very rare entity with no definite treatment protocol. Herein, we describe one such case with discussion of its diagnosis and management. The patient had a well circumscribed mass in right kidney extending into the inferior vena cava and metastasis to both the lungs. Right nephrectomy was performed and the histopathological examination confirmed the diagnosis to be renal mesenchymal chondrosarcoma. After surgical removal of the tumor, the patient was given chemotherapy with Cisplatin and Epirubicin, following which there was significant regression of lung nodules.

  5. Chinese herbs and their active ingredients for activating xue (blood) promote the proliferation and differentiation of neural stem cells and mesenchymal stem cells.

    Science.gov (United States)

    Si, Yin-Chu; Li, Qiang; Xie, Chun-E; Niu, Xin; Xia, Xiao-Hui; Yu, Chang-Yuan

    2014-04-09

    Some Chinese herbs are anti-thrombolysis, and anti-inflammatory, improves brain RNA content, promotes brain protein synthesis, enhances dopamine function, regulates brain hormones, and improves microcirculation in central nervous system that might improve, repair and rehabilitation from the stroke and brain injury. Specific Chinese herbs and their components, such as Acanthopanax, Angelica, could maintain the survival of neural stem cells, and Rhodiola, Ganoderma spore Polygala, Tetramethylpyrazine, Gardenia, Astragaloside and Ginsenoside Rg1 promoted proliferation of neural stem cells, and Rhodiola, Astragaloside promoted differentiation of neural stem cell into neuron and glia in vivo. Astragalus, Safflower, Musk, Baicalin, Geniposide, Ginkgolide B, Cili polysaccharide, Salidroside, Astragaloside, Antler polypeptides, Ginsenoside Rg1, Panax notoginseng saponins promoted proliferation and differentiation of neural stem cells in vitro. Salvia, Astragalus, Ginsenoside Rg1, P. notoginseng saponins, Musk polypeptide, Muscone and Ginkgolide B promoted neural-directed differentiation of MSCs into nerve cells. These findings are encouraging further research into the Chinese herbs for developing drugs in treating patients of stroke and brain injury.

  6. Human mesenchymal stem cells

    DEFF Research Database (Denmark)

    Abdallah, Basem; Kassem, Moustapha

    2008-01-01

    introduced into clinical medicine in variety of applications and through different ways of administration. Here, we discuss approaches for isolation, characterization and directing differentiation of human mesenchymal stem cells (hMSC). An update of the current clinical use of the cells is also provided....

  7. Chinese herbs and their active ingredients for activating xue (blood) promote the proliferation and differentiation of neural stem cells and mesenchymal stem cells

    OpenAIRE

    Si, Yin-chu; Li, Qiang; Xie, Chun-e; NIU, Xin; Xia, Xiao-hui; Yu, Chang-Yuan

    2014-01-01

    Some Chinese herbs are anti-thrombolysis, and anti-inflammatory, improves brain RNA content, promotes brain protein synthesis, enhances dopamine function, regulates brain hormones, and improves microcirculation in central nervous system that might improve, repair and rehabilitation from the stroke and brain injury. Specific Chinese herbs and their components, such as Acanthopanax, Angelica, could maintain the survival of neural stem cells, and Rhodiola, Ganoderma spore Polygala, Tetramethylpy...

  8. Investigating the link between molecular subtypes of glioblastoma, epithelial-mesenchymal transition, and CD133 cell surface protein.

    Directory of Open Access Journals (Sweden)

    Hadi Zarkoob

    Full Text Available In this manuscript, we use genetic data to provide a three-faceted analysis on the links between molecular subclasses of glioblastoma, epithelial-to-mesenchymal transition (EMT and CD133 cell surface protein. The contribution of this paper is three-fold: First, we use a newly identified signature for epithelial-to-mesenchymal transition in human mammary epithelial cells, and demonstrate that genes in this signature have significant overlap with genes differentially expressed in all known GBM subtypes. However, the overlap between genes up regulated in the mesenchymal subtype of GBM and in the EMT signature was more significant than other GBM subtypes. Second, we provide evidence that there is a negative correlation between the genetic signature of EMT and that of CD133 cell surface protein, a putative marker for neural stem cells. Third, we study the correlation between GBM molecular subtypes and the genetic signature of CD133 cell surface protein. We demonstrate that the mesenchymal and neural subtypes of GBM have the strongest correlations with the CD133 genetic signature. While the mesenchymal subtype of GBM displays similarity with the signatures of both EMT and CD133, it also exhibits some differences with each of these signatures that are partly due to the fact that the signatures of EMT and CD133 are inversely related to each other. Taken together these data shed light on the role of the mesenchymal transition and neural stem cells, and their mutual interaction, in molecular subtypes of glioblastoma multiforme.

  9. Hectd1 regulates intracellular localization and secretion of Hsp90 to control cellular behavior of the cranial mesenchyme.

    Science.gov (United States)

    Sarkar, Anjali A; Zohn, Irene E

    2012-03-19

    Hectd1 mutant mouse embryos exhibit the neural tube defect exencephaly associated with abnormal cranial mesenchyme. Cellular rearrangements in cranial mesenchyme are essential during neurulation for elevation of the neural folds. Here we investigate the molecular basis of the abnormal behavior of Hectd1 mutant cranial mesenchyme. We demonstrate that Hectd1 is a functional ubiquitin ligase and that one of its substrates is Hsp90, a chaperone protein with both intra- and extracellular clients. Extracellular Hsp90 enhances migration of multiple cell types. In mutant cranial mesenchyme cells, both secretion of Hsp90 and emigration of cells from cranial mesenchyme explants were enhanced. Importantly, we show that this enhanced emigration was highly dependent on the excess Hsp90 secreted from mutant cells. Together, our data set forth a model whereby increased secretion of Hsp90 in the cranial mesenchyme of Hectd1 mutants is responsible, at least in part, for the altered organization and behavior of these cells and provides a potential molecular mechanism underlying the neural tube defect.

  10. [Mesenchymal chondrosarcoma of the mandible].

    Science.gov (United States)

    Bencheikh, R; Benhammou, A; Benbouzid, M-A; El Edghiri, H; Boulaich, M; Essakali, L; Kzadri, M

    2007-04-01

    Mesenchymal chondrosarcoma is a rare form of chondrosarcoma and mandibular localization is rare. We report a case of mesenchymal chondrosarcoma of the mandible in a 23-year-old patient who consulted for a voluminous tumor of the right mandible. Radiological findings suggested a malignant tumor. A hemimandibulectomy and a pelvectomy were performed. The histological assessment showed zones of neoplastic cartilage and small ovoid cells, typical of mesenchymal chondrosarcoma. Mesenchymal chondrosarcoma is a rare malignant tumor of skeletal and extra skeletal origin. The most frequent localizations are the femur, the ribs, and facial bones. Histologically, these tumors have a typical biphasic pattern consisting of both small cells and islands of atypical cartilage. Because of its rich vascular component, this lesion has often been confused with hemangiopericytoma. Surgery is the usual treatment. The prognosis is very poor with a high risk of relapse and metastasis.

  11. Fibulin-5 deficiency causes developmental defect of premaxillary bone in mice

    Energy Technology Data Exchange (ETDEWEB)

    Noda, Kazuo, E-mail: knoda@kuhp.kyoto-u.ac.jp [Department of Pediatrics, The University of Texas Medical School at Houston, Houston, TX 77030 (United States); Nakamura, Tomoyuki [Department of Pharmacology, Kansai Medical University, Hirakata, Osaka 573-1010 (Japan); Komatsu, Yoshihiro [Department of Pediatrics, The University of Texas Medical School at Houston, Houston, TX 77030 (United States); Graduate Program in Genes and Development, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX 77030 (United States)

    2015-10-23

    Craniofacial sutures govern the shape of the craniofacial skeleton during postnatal development. The differentiation of suture mesenchymal cells to osteoblasts is precisely regulated in part by signaling through cell surface receptors that interact with extracellular proteins. Here we report that fibulin-5, a key extracellular matrix protein, is important for craniofacial skeletal development in mice. Fibulin-5 is deposited as a fibrous matrix in cranial neural crest-derived mesenchymal tissues, including craniofacial sutures. Fibulin-5-null mice show decreased premaxillary bone outgrowth during postnatal stages. While premaxillo-maxillary suture mesenchymal cells in fibulin-5-null mice were capable of differentiating into osteoblasts, suture cells in mutant mice were less proliferative. Our study provides the first evidence that fibulin-5 is indispensable for the regulation of facial suture mesenchymal cell proliferation required for craniofacial skeletal morphogenesis. - Highlights: • Fibulin-5 is deposited in cranial neural crest-derived mesenchymal tissues. • Fibulin-5-null mice show decreased premaxillary bone growth during postnatal stage. • Fibulin-5 is indispensable for facial suture mesenchymal cell proliferation.

  12. Zebrafish zic2 controls formation of periocular neural crest and choroid fissure morphogenesis.

    Science.gov (United States)

    Sedykh, Irina; Yoon, Baul; Roberson, Laura; Moskvin, Oleg; Dewey, Colin N; Grinblat, Yevgenya

    2017-09-01

    The vertebrate retina develops in close proximity to the forebrain and neural crest-derived cartilages of the face and jaw. Coloboma, a congenital eye malformation, is associated with aberrant forebrain development (holoprosencephaly) and with craniofacial defects (frontonasal dysplasia) in humans, suggesting a critical role for cross-lineage interactions during retinal morphogenesis. ZIC2, a zinc-finger transcription factor, is linked to human holoprosencephaly. We have previously used morpholino assays to show zebrafish zic2 functions in the developing forebrain, retina and craniofacial cartilage. We now report that zebrafish with genetic lesions in zebrafish zic2 orthologs, zic2a and zic2b, develop with retinal coloboma and craniofacial anomalies. We demonstrate a requirement for zic2 in restricting pax2a expression and show evidence that zic2 function limits Hh signaling. RNA-seq transcriptome analysis identified an early requirement for zic2 in periocular neural crest as an activator of alx1, a transcription factor with essential roles in craniofacial and ocular morphogenesis in human and zebrafish. Collectively, these data establish zic2 mutant zebrafish as a powerful new genetic model for in-depth dissection of cell interactions and genetic controls during craniofacial complex development. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Differentiation of mesenchymal stem cells into neuronal cells on fetal bovine acellular dermal matrix as a tissue engineered nerve scaffold

    Science.gov (United States)

    Feng, Yuping; Wang, Jiao; Ling, Shixin; Li, Zhuo; Li, Mingsheng; Li, Qiongyi; Ma, Zongren; Yu, Sijiu

    2014-01-01

    The purpose of this study was to assess fetal bovine acellular dermal matrix as a scaffold for supporting the differentiation of bone marrow mesenchymal stem cells into neural cells following induction with neural differentiation medium. We performed long-term, continuous observation of cell morphology, growth, differentiation, and neuronal development using several microscopy techniques in conjunction with immunohistochemistry. We examined specific neuronal proteins and Nissl bodies involved in the differentiation process in order to determine the neuronal differentiation of bone marrow mesenchymal stem cells. The results show that bone marrow mesenchymal stem cells that differentiate on fetal bovine acellular dermal matrix display neuronal morphology with unipolar and bi/multipolar neurite elongations that express neuronal-specific proteins, including βIII tubulin. The bone marrow mesenchymal stem cells grown on fetal bovine acellular dermal matrix and induced for long periods of time with neural differentiation medium differentiated into a multilayered neural network-like structure with long nerve fibers that was composed of several parallel microfibers and neuronal cells, forming a complete neural circuit with dendrite-dendrite to axon-dendrite to dendrite-axon synapses. In addition, growth cones with filopodia were observed using scanning electron microscopy. Paraffin sectioning showed differentiated bone marrow mesenchymal stem cells with the typical features of neuronal phenotype, such as a large, round nucleus and a cytoplasm full of Nissl bodies. The data suggest that the biological scaffold fetal bovine acellular dermal matrix is capable of supporting human bone marrow mesenchymal stem cell differentiation into functional neurons and the subsequent formation of tissue engineered nerve. PMID:25598779

  14. OVOL2 Maintains the Transcriptional Program of Human Corneal Epithelium by Suppressing Epithelial-to-Mesenchymal Transition

    Directory of Open Access Journals (Sweden)

    Koji Kitazawa

    2016-05-01

    Full Text Available In development, embryonic ectoderm differentiates into neuroectoderm and surface ectoderm using poorly understood mechanisms. Here, we show that the transcription factor OVOL2 maintains the transcriptional program of human corneal epithelium cells (CECs, a derivative of the surface ectoderm, and that OVOL2 may regulate the differential transcriptional programs of the two lineages. A functional screen identified OVOL2 as a repressor of mesenchymal genes to maintain CECs. Transduction of OVOL2 with several other transcription factors induced the transcriptional program of CECs in fibroblasts. Moreover, neuroectoderm derivatives were found to express mesenchymal genes, and OVOL2 alone could induce the transcriptional program of CECs in neural progenitors by repressing these genes while activating epithelial genes. Our data suggest that the difference between the transcriptional programs of some neuroectoderm- and surface ectoderm-derivative cells may be regulated in part by a reciprocally repressive mechanism between epithelial and mesenchymal genes, as seen in epithelial-to-mesenchymal transition.

  15. The role of catecholamines in mesenchymal stem cell fate.

    Science.gov (United States)

    Hajifathali, Abbas; Saba, Fakhredin; Atashi, Amir; Soleimani, Masoud; Mortaz, Esmaeil; Rasekhi, Mahsa

    2014-12-01

    Mesenchymal stem cells (MSCs) are multipotent stem cells found in many adult tissues, especially bone marrow (BM) and are capable of differentiation into various lineage cells such as osteoblasts, adipocytes, chondrocytes and myocytes. Moreover, MSCs can be mobilized from connective tissue into circulation and from there to damaged sites to contribute to regeneration processes. MSCs commitment and differentiation are controlled by complex activities involving signal transduction through cytokines and catecholamines. There has been an increasing interest in recent years in the neural system, functioning in the support of stem cells like MSCs. Recent efforts have indicated that the catecholamine released from neural and not neural cells could be affected characteristics of MSCs. However, there have not been review studies of most aspects involved in catecholamines-mediated functions of MSCs. Thus, in this review paper, we will try to describe the current state of catecholamines in MSCs destination and discuss strategies being used for catecholamines for migration of these cells to damaged tissues. Then, the role of the nervous system in the induction of osteogenesis, adipogenesis, chondrogenesis and myogenesis from MSCs is discussed. Recent progress in studies of signaling transduction of catecholamines in determination of the final fate of MSCs is highlighted. Hence, the knowledge of interaction between MSCs with the neural system could be applied towards the development of new diagnostic and treatment alternatives for human diseases.

  16. Deletion of integrin-linked kinase from neural crest cells in mice results in aortic aneurysms and embryonic lethality

    Directory of Open Access Journals (Sweden)

    Thomas D. Arnold

    2013-09-01

    Neural crest cells (NCCs participate in the remodeling of the cardiac outflow tract and pharyngeal arch arteries during cardiovascular development. Integrin-linked kinase (ILK is a serine/threonine kinase and a major regulator of integrin signaling. It links integrins to the actin cytoskeleton and recruits other adaptor molecules into a large complex to regulate actin dynamics and integrin function. Using the Cre-lox system, we deleted Ilk from NCCs of mice to investigate its role in NCC morphogenesis. The resulting mutants developed a severe aneurysmal arterial trunk that resulted in embryonic lethality during late gestation. Ilk mutants showed normal cardiac NCC migration but reduced differentiation into smooth muscle within the aortic arch arteries and the outflow tract. Within the conotruncal cushions, Ilk-deficient NCCs exhibited disorganization of F-actin stress fibers and a significantly rounder morphology, with shorter cellular projections. Additionally, absence of ILK resulted in reduced in vivo phosphorylation of Smad3 in NCCs, which correlated with reduced αSMA levels. Our findings resemble those seen in Pinch1 and β1 integrin conditional mutant mice, and therefore support that, in neural crest-derived cells, ILK and Pinch1 act as cytoplasmic effectors of β1 integrin in a pathway that protects against aneurysms. In addition, our conditional Ilk mutant mice might prove useful as a model to study aortic aneurysms caused by reduced Smad3 signaling, as occurs in the newly described aneurysms-osteoarthritis syndrome, for example.

  17. Mesenchymal progenitor cells for the osteogenic lineage.

    Science.gov (United States)

    Ono, Noriaki; Kronenberg, Henry M

    2015-09-01

    Mesenchymal progenitors of the osteogenic lineage provide the flexibility for bone to grow, maintain its function and homeostasis. Traditionally, colony-forming-unit fibroblasts (CFU-Fs) have been regarded as surrogates for mesenchymal progenitors; however, this definition cannot address the function of these progenitors in their native setting. Transgenic murine models including lineage-tracing technologies based on the cre-lox system have proven to be useful in delineating mesenchymal progenitors in their native environment. Although heterogeneity of cell populations of interest marked by a promoter-based approach complicates overall interpretation, an emerging complexity of mesenchymal progenitors has been revealed. Current literatures suggest two distinct types of bone progenitor cells; growth-associated mesenchymal progenitors contribute to explosive growth of bone in early life, whereas bone marrow mesenchymal progenitors contribute to the much slower remodeling process and response to injury that occurs mainly in adulthood. More detailed relationships of these progenitors need to be studied through further experimentation.

  18. Lack of Motor Neuron Differentiation is an Intrinsic Property of the Mouse Secondary Neural Tube

    Science.gov (United States)

    Shum, Alisa S.W.; Tang, Louisa S.C.; Copp, Andrew J.; Roelink, Henk

    2016-01-01

    The cranial part of the amniote neural tube is formed by folding and fusion of the ectoderm-derived neural plate (primary neurulation). After posterior neuropore closure, however, the caudal neural tube is formed by cavitation of tail bud mesenchyme (secondary neurulation). In mouse embryos, the secondary neural tube expresses several genes important in early patterning and induction, in restricted domains similar to the primary neural tube, yet it does not undergo neuronal differentiation, but subsequently degenerates. Although the secondary neural tube, isolated from surrounding tissues, is responsive to exogenous Sonic Hedgehog proteins in vitro, motor neuron differentiation is never observed. This cannot be attributed to the properties of the secondary notochord, since it is able to induce motor neuron differentiation in naïve chick neural plate explants. Taken together, these results support that the lack of motor neuron differentiation is an intrinsic property of the mouse secondary neural tube. PMID:20960561

  19. Neural crest specification: tissues, signals, and transcription factors.

    Science.gov (United States)

    Rogers, C D; Jayasena, C S; Nie, S; Bronner, M E

    2012-01-01

    The neural crest is a transient population of multipotent and migratory cells unique to vertebrate embryos. Initially derived from the borders of the neural plate, these cells undergo an epithelial to mesenchymal transition to leave the central nervous system, migrate extensively in the periphery, and differentiate into numerous diverse derivatives. These include but are not limited to craniofacial cartilage, pigment cells, and peripheral neurons and glia. Attractive for their similarities to stem cells and metastatic cancer cells, neural crest cells are a popular model system for studying cell/tissue interactions and signaling factors that influence cell fate decisions and lineage transitions. In this review, we discuss the mechanisms required for neural crest formation in various vertebrate species, focusing on the importance of signaling factors from adjacent tissues and conserved gene regulatory interactions, which are required for induction and specification of the ectodermal tissue that will become neural crest. Copyright © 2011 Wiley Periodicals, Inc.

  20. Evolvable synthetic neural system

    Science.gov (United States)

    Curtis, Steven A. (Inventor)

    2009-01-01

    An evolvable synthetic neural system includes an evolvable neural interface operably coupled to at least one neural basis function. Each neural basis function includes an evolvable neural interface operably coupled to a heuristic neural system to perform high-level functions and an autonomic neural system to perform low-level functions. In some embodiments, the evolvable synthetic neural system is operably coupled to one or more evolvable synthetic neural systems in a hierarchy.

  1. Pancreatic mesenchyme regulates epithelial organogenesis throughout development.

    Directory of Open Access Journals (Sweden)

    Limor Landsman

    2011-09-01

    Full Text Available The developing pancreatic epithelium gives rise to all endocrine and exocrine cells of the mature organ. During organogenesis, the epithelial cells receive essential signals from the overlying mesenchyme. Previous studies, focusing on ex vivo tissue explants or complete knockout mice, have identified an important role for the mesenchyme in regulating the expansion of progenitor cells in the early pancreas epithelium. However, due to the lack of genetic tools directing expression specifically to the mesenchyme, the potential roles of this supporting tissue in vivo, especially in guiding later stages of pancreas organogenesis, have not been elucidated. We employed transgenic tools and fetal surgical techniques to ablate mesenchyme via Cre-mediated mesenchymal expression of Diphtheria Toxin (DT at the onset of pancreas formation, and at later developmental stages via in utero injection of DT into transgenic mice expressing the Diphtheria Toxin receptor (DTR in this tissue. Our results demonstrate that mesenchymal cells regulate pancreatic growth and branching at both early and late developmental stages by supporting proliferation of precursors and differentiated cells, respectively. Interestingly, while cell differentiation was not affected, the expansion of both the endocrine and exocrine compartments was equally impaired. To further elucidate signals required for mesenchymal cell function, we eliminated β-catenin signaling and determined that it is a critical pathway in regulating mesenchyme survival and growth. Our study presents the first in vivo evidence that the embryonic mesenchyme provides critical signals to the epithelium throughout pancreas organogenesis. The findings are novel and relevant as they indicate a critical role for the mesenchyme during late expansion of endocrine and exocrine compartments. In addition, our results provide a molecular mechanism for mesenchymal expansion and survival by identifying β-catenin signaling as an

  2. Characterization of mesenchymal progenitor cell populations from non-epithelial oral mucosa.

    Science.gov (United States)

    Matsumura, S; Higa, K; Igarashi, T; Takaichi, S; Tonogi, M; Shinozaki, N; Shimazaki, J; Yamane, G-y

    2015-04-01

    The characteristics of cell populations extracted from oral mucosal non-epithelial tissues and their ability to differentiate were evaluated in vitro as a potential source of cells for mandibular and corneal regeneration. Oral mucosal non-epithelial cells (OMNECs) were extracted from tissue samples and were studied by flow cytometry and RT-PCR. Cells differentiating into osteoblasts, adipocytes, chondrocytes, neurocytes, or keratocytes were characterized by RT-PCR and cell staining. OMNECs expressed CD44, CD90, CD105, CD166, and STRO-1 antigens, which are markers for mesenchymal stem cells. In addition, Oct3/4, c-Myc, Nanog, KLF4, and Rex, which are expressed by embryonic or pluripotent stem cells, were detected by RT-PCR. Expression of CD49d, CD56, and PDGFRα, proteins closely associated with the neural crest, was observed in OMNECs, as was expression of Twist1, Sox9, Snail1 and Snail2, which are early neural crest and neural markers. Specific differentiation markers were expressed in OMNECs after differentiation into osteoblasts, adipocytes, chondrocytes, or keratocytes. Populations of OMNECs may contain both mesenchymal stem cells and neural crest origin cells and are a potential cell source for autologous regeneration of mandibular or corneal stroma. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. Effects of tissue age, presence of neurones and endothelin-3 on the ability of enteric neurone precursors to colonize recipient gut: implications for cell-based therapies.

    Science.gov (United States)

    Hotta, R; Anderson, R B; Kobayashi, K; Newgreen, D F; Young, H M

    2010-03-01

    BACKGROUND Most enteric neurones arise from neural crest cells that originate in the post-otic hindbrain, and migrate into and along the developing gastrointestinal tract. There is currently great interest in the possibility of cell therapy to replace diseased or absent enteric neurones in patients with enteric neuropathies, such as Hirschsprung's disease. However, it is unclear whether neural crest stem/progenitor cells will be able to colonize colon (i) in which the mesenchyme has differentiated into distinct layers, (ii) that already contains enteric neurones or (iii) that lacks a gene expressed by the gut mesenchyme, such as endothelin-3 (Et-3). METHODS Co-cultures were used to examine the ability of enteric neural crest-derived cells (ENCCs) from E11.5 mouse gut to colonize a variety of recipient hindguts. KEY RESULTS Enteric neural crest-derived cells migrated and gave rise to neurones in E14.5 and E16.5 aneural colon in which the external muscle layers had differentiated, but they did not migrate as far as in younger colon. There was no evidence of altered ENCC proliferation, cell death or neuronal differentiation in older recipient explants. Enteric neural crest-derived cells failed to enter most recipient E14.5 and E16.5 colon explants already containing enteric neurones, and the few that did showed very limited migration. Finally, ENCCs migrated a shorter distance and a higher proportion expressed the pan-neuronal marker, Hu, in recipient E11.5 Et-3(-/-) colon compared to wild-type recipient colon. CONCLUSIONS & INFERENCES Age and an absence of Et-3 from the recipient gut both significantly reduced but did not prevent ENCC migration, but the presence of neurones almost totally prevented ENCC migration.

  4. Cranial muscles in amphibians: development, novelties and the role of cranial neural crest cells

    Science.gov (United States)

    Schmidt, Jennifer; Piekarski, Nadine; Olsson, Lennart

    2013-01-01

    Our research on the evolution of the vertebrate head focuses on understanding the developmental origins of morphological novelties. Using a broad comparative approach in amphibians, and comparisons with the well-studied quail-chicken system, we investigate how evolutionarily conserved or variable different aspects of head development are. Here we review research on the often overlooked development of cranial muscles, and on its dependence on cranial cartilage development. In general, cranial muscle cell migration and the spatiotemporal pattern of cranial muscle formation appears to be very conserved among the few species of vertebrates that have been studied. However, fate-mapping of somites in the Mexican axolotl revealed differences in the specific formation of hypobranchial muscles (tongue muscles) in comparison to the chicken. The proper development of cranial muscles has been shown to be strongly dependent on the mostly neural crest-derived cartilage elements in the larval head of amphibians. For example, a morpholino-based knock-down of the transcription factor FoxN3 in Xenopus laevis has drastic indirect effects on cranial muscle patterning, although the direct function of the gene is mostly connected to neural crest development. Furthermore, extirpation of single migratory streams of cranial neural crest cells in combination with fate-mapping in a frog shows that individual cranial muscles and their neural crest-derived connective tissue attachments originate from the same visceral arch, even when the muscles attach to skeletal components that are derived from a different arch. The same pattern has also been found in the chicken embryo, the only other species that has been thoroughly investigated, and thus might be a conserved pattern in vertebrates that reflects the fundamental nature of a mechanism that keeps the segmental order of the head in place despite drastic changes in adult anatomy. There is a need for detailed comparative fate-mapping of pre

  5. Cranial muscles in amphibians: development, novelties and the role of cranial neural crest cells.

    Science.gov (United States)

    Schmidt, Jennifer; Piekarski, Nadine; Olsson, Lennart

    2013-01-01

    Our research on the evolution of the vertebrate head focuses on understanding the developmental origins of morphological novelties. Using a broad comparative approach in amphibians, and comparisons with the well-studied quail-chicken system, we investigate how evolutionarily conserved or variable different aspects of head development are. Here we review research on the often overlooked development of cranial muscles, and on its dependence on cranial cartilage development. In general, cranial muscle cell migration and the spatiotemporal pattern of cranial muscle formation appears to be very conserved among the few species of vertebrates that have been studied. However, fate-mapping of somites in the Mexican axolotl revealed differences in the specific formation of hypobranchial muscles (tongue muscles) in comparison to the chicken. The proper development of cranial muscles has been shown to be strongly dependent on the mostly neural crest-derived cartilage elements in the larval head of amphibians. For example, a morpholino-based knock-down of the transcription factor FoxN3 in Xenopus laevis has drastic indirect effects on cranial muscle patterning, although the direct function of the gene is mostly connected to neural crest development. Furthermore, extirpation of single migratory streams of cranial neural crest cells in combination with fate-mapping in a frog shows that individual cranial muscles and their neural crest-derived connective tissue attachments originate from the same visceral arch, even when the muscles attach to skeletal components that are derived from a different arch. The same pattern has also been found in the chicken embryo, the only other species that has been thoroughly investigated, and thus might be a conserved pattern in vertebrates that reflects the fundamental nature of a mechanism that keeps the segmental order of the head in place despite drastic changes in adult anatomy. There is a need for detailed comparative fate-mapping of pre

  6. Human stromal (mesenchymal) stem cells

    DEFF Research Database (Denmark)

    Aldahmash, Abdullah; Zaher, Walid; Al-Nbaheen, May

    2012-01-01

    Human stromal (mesenchymal) stem cells (hMSC) represent a group of non-hematopoietic stem cells present in the bone marrow stroma and the stroma of other organs including subcutaneous adipose tissue, placenta, and muscles. They exhibit the characteristics of somatic stem cells of self......-renewal and multi-lineage differentiation into mesoderm-type of cells, e.g., to osteoblasts, adipocytes, chondrocytes and possibly other cell types including hepatocytes and astrocytes. Due to their ease of culture and multipotentiality, hMSC are increasingly employed as a source for cells suitable for a number...

  7. Alternative Routes to Induced Pluripotent Stem Cells Revealed by Reprogramming of the Neural Lineage

    OpenAIRE

    Jackson, Steven A.; Zachariah P.G. Olufs; Tran, Khoa A.; Zaidan, Nur Zafirah; Sridharan, Rupa

    2016-01-01

    Summary During the reprogramming of mouse embryonic fibroblasts (MEFs) to induced pluripotent stem cells, the activation of pluripotency genes such as NANOG occurs after the mesenchymal to epithelial transition. Here we report that both adult stem cells (neural stem cells) and differentiated cells (astrocytes) of the neural lineage can activate NANOG in the absence of cadherin expression during reprogramming. Gene expression analysis revealed that only the NANOG+E-cadherin+ populations expres...

  8. Mesenchymal stem cells in osteoarthritis.

    Science.gov (United States)

    Luyten, Frank P

    2004-09-01

    Accumulating evidence indicates that every tissue contains stem cells. Our understanding of the biology of stem cells reveals that these cell populations have a critical role in the homeostasis and repair of tissues. Besides the local stem cell niches, additional compartments in the body such as the bone marrow may serve as reservoirs for stem cell populations. On more extensive tissue damage, and guided by local repair responses, "reparative" cell populations are mobilized from more distant stem cell reservoirs and migrate to the site of injury, thereby contributing in many aspects of local tissue repair. Osteoarthritis has long been regarded as an imbalance between destructive and reparative processes. The lack of repair of the weight-bearing articular cartilage and the associated subchondral bone changes are considered of critical importance in the progression of the disease. Recent findings indicate a depletion and/or functional alteration of mesenchymal stem cell populations in osteoarthritis. These preliminary data suggest that in joint diseases such as osteoarthritis, it is of importance to investigate further the involvement of the stem cell pool in the mechanisms contributing to joint homeostasis and driving disease progression. In view of the emerging body of evidence pointing to a potential therapeutic utility of stem cell technology, it is not surprising that local delivery of mesenchymal stem cells has been explored as a therapeutic approach in animal models of osteoarthritis. Copyright 2004 Lippincott Williams & Wilkins

  9. Central nervous system mesenchymal chondrosarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Salvati, M.; Frati, A.; Piccirilli, M.; Agrillo, A.; Brogna, C.; Occhiogrosso, G.; Giangaspero, F. [INM Neuromed IRCCS, Pozzilli (Italy). Dept. of Neurosurgery; Caroli, E. [Policlinico S. Andrea, Rome (Italy). Dept. of Neurological Sciences, Neurosurgery

    2005-06-15

    Central nervous system mesenchymal chondrosarcomas are rare malignant tumors that constitute a separate entity from the classical chondrosarcoma and myxoid variant. Clinical behaviour of central nervous system chondrosarcomas is still unknown. We describe two rare examples of intracranial mesenchymal chondrosarcoma with a review of the literature, in an attempt to clarify the clinical characteristics, prognosis and treatment of choice of these unusual tumors. Among the 55 reported cases, 23 had postoperative radiotherapy. Although there is no statistical significance according to the Log-Rank test (p=0.7), the patients treated with radiation therapy seem to have a better chance of survival. Patients who had adjuvant chemotherapy (only 5) showed survival times similar to those patients who had none. Although clinical behaviour of central nervous system chondrosarcomas remains to be defined, data from our series as well as literature show that radical removal is the best therapeutic choice. In addition, patients treated with postoperative radiotherapy seem to show a trend toward increased survival.

  10. Migratory properties of mesenchymal stem cells.

    Science.gov (United States)

    Dittmar, Thomas; Entschladen, Frank

    2013-01-01

    Mesenchymal stem cells raise great expectations in regenerative medicine due to their capacity to regenerate damaged tissues, thereby restoring organ tissue integrity and functionality. Even though it is not yet clear how mesenchymal stem cells are guided to injured tissue it is generally assumed that the directed migration of these cells is facilitated by the same soluble factors that also recruit immune competent cells to inflamed tissue areas. Tumor tissue represents another type of (chronically) inflamed tissue and because of that mesenchymal stem cells are highly attracted. Although some data indicate that esenchymal stem cells might have a beneficial effect on tumor growth due to anti-tumor effects the plethora of data suggest that tumor tissue recruited mesenchymal stem cells rather promote tumor growth and metastasis formation. Nonetheless, the enhanced tumor tropism of mesenchymal stem cells makes them ideal candidates for novel anti-cancer strategies. Like Trojan Horses genetically modified mesenchymal stem cells will deliver their deadly cargo, such as anti-tumor cytokines or oncolytic viruses, into cancerous tissues, thereby destroying the tumor form within. In this chapter we will summarize the current concepts of genetic modification of mesenchymal stem cells for future anti-cancer therapies.

  11. Autism Spectrum Disorders: Is Mesenchymal Stem Cell Personalized Therapy the Future?

    Directory of Open Access Journals (Sweden)

    Dario Siniscalco

    2012-01-01

    Full Text Available Autism and autism spectrum disorders (ASDs are heterogeneous neurodevelopmental disorders. They are enigmatic conditions that have their origins in the interaction of genes and environmental factors. ASDs are characterized by dysfunctions in social interaction and communication skills, in addition to repetitive and stereotypic verbal and nonverbal behaviours. Immune dysfunction has been confirmed with autistic children. There are no defined mechanisms of pathogenesis or curative therapy presently available. Indeed, ASDs are still untreatable. Available treatments for autism can be divided into behavioural, nutritional, and medical approaches, although no defined standard approach exists. Nowadays, stem cell therapy represents the great promise for the future of molecular medicine. Among the stem cell population, mesenchymal stem cells (MSCs show probably best potential good results in medical research. Due to the particular immune and neural dysregulation observed in ASDs, mesenchymal stem cell transplantation could offer a unique tool to provide better resolution for this disease.

  12. Expression of the chitinase family glycoprotein YKL-40 in undifferentiated, differentiated and trans-differentiated mesenchymal stem cells.

    Directory of Open Access Journals (Sweden)

    Daniel J Hoover

    Full Text Available The glycoprotein YKL-40 (CHI3L1 is a secreted chitinase family protein that induces angiogenesis, cell survival, and cell proliferation, and plays roles in tissue remodeling and immune regulation. It is expressed primarily in cells of mesenchymal origin, is overexpressed in numerous aggressive carcinomas and sarcomas, but is rarely expressed in normal ectodermal tissues. Bone marrow-derived mesenchymal stem cells (MSCs can be induced to differentiate into various mesenchymal tissues and trans-differentiate into some non-mesenchymal cell types. Since YKL-40 has been used as a mesenchymal marker, we followed YKL-40 expression as undifferentiated MSCs were induced to differentiate into bone, cartilage, and neural phenotypes. Undifferentiated MSCs contain significant levels of YKL-40 mRNA but do not synthesize detectable levels of YKL-40 protein. MSCs induced to differentiate into chondrocytes and osteocytes soon began to express and secrete YKL-40 protein, as do ex vivo cultured chondrocytes and primary osteocytes. In contrast, MSCs induced to trans-differentiate into neurons did not synthesize YKL-40 protein, consistent with the general absence of YKL-40 protein in normal CNS parenchyma. However, these trans-differentiated neurons retained significant levels of YKL-40 mRNA, suggesting the mechanisms which prevented YKL-40 translation in undifferentiated MSCs remained in place, and that these trans-differentiated neurons differ in at least this way from neurons derived from neuronal stem cells. Utilization of a differentiation protocol containing β-mercaptoethanol resulted in cells that expressed significant amounts of intracellular YKL-40 protein that was not secreted, which is not seen in normal cells. Thus the synthesis of YKL-40 protein is a marker for MSC differentiation into mature mesenchymal phenotypes, and the presence of untranslated YKL-40 mRNA in non-mesenchymal cells derived from MSCs reflects differences between differentiated and

  13. Neural Networks

    Directory of Open Access Journals (Sweden)

    Schwindling Jerome

    2010-04-01

    Full Text Available This course presents an overview of the concepts of the neural networks and their aplication in the framework of High energy physics analyses. After a brief introduction on the concept of neural networks, the concept is explained in the frame of neuro-biology, introducing the concept of multi-layer perceptron, learning and their use as data classifer. The concept is then presented in a second part using in more details the mathematical approach focussing on typical use cases faced in particle physics. Finally, the last part presents the best way to use such statistical tools in view of event classifers, putting the emphasis on the setup of the multi-layer perceptron. The full article (15 p. corresponding to this lecture is written in french and is provided in the proceedings of the book SOS 2008.

  14. Roles of Mesenchymal Stem Cells in Spinal Cord Injury

    Directory of Open Access Journals (Sweden)

    Jing Qu

    2017-01-01

    Full Text Available Spinal cord injury (SCI represents one of the most complicated and heterogeneous pathological processes of central nervous system (CNS impairments, which is still beyond functional regeneration. Transplantation of mesenchymal stem cells (MSCs has been shown to promote the repair of the injured spinal cord tissues in animal models, and therefore, there is much interest in the clinical use of these cells. However, many questions which are essential to improve the therapy effects remain unanswered. For instance, the functional roles and related molecular regulatory mechanisms of MSCs in vivo are not yet completely determined. It is important for transplanted cells to migrate into the injured tissue, to survive and undergo neural differentiation, or to play neural protection roles by various mechanisms after SCI. In this review, we will focus on some of the recent knowledge about the biological behavior and function of MSCs in SCI. Meanwhile, we highlight the function of biomaterials to direct the behavior of MSCs based on our series of work on silk fibroin biomaterials and attempt to emphasize combinational strategies such as tissue engineering for functional improvement of SCI.

  15. Mesenchymal chondrosarcoma--a case report.

    Directory of Open Access Journals (Sweden)

    Tyagi S

    1992-01-01

    Full Text Available A Case of extraosseous mesenchymal chondrosarcoma occurring in the occipital region in a 26 year old male is being reported. The patient remained free from recurrence on any metastasis even after 2 years of the tumor resection.

  16. Regulation of pulmonary inflammation by mesenchymal cells

    NARCIS (Netherlands)

    Alkhouri, Hatem; Poppinga, Wilfred Jelco; Tania, Navessa Padma; Ammit, Alaina; Schuliga, Michael

    2014-01-01

    Pulmonary inflammation and tissue remodelling are common elements of chronic respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), and pulmonary hypertension (PH). In disease, pulmonary mesenchymal cells not only contribute to tissue

  17. Neural Tube Defects

    Science.gov (United States)

    ... vitamin, before and during pregnancy prevents most neural tube defects. Neural tube defects are usually diagnosed before the infant is ... or imaging tests. There is no cure for neural tube defects. The nerve damage and loss of function ...

  18. Mesenchymal stem cells avoid allogeneic rejection

    Directory of Open Access Journals (Sweden)

    Murphy J Mary

    2005-07-01

    Full Text Available Abstract Adult bone marrow derived mesenchymal stem cells offer the potential to open a new frontier in medicine. Regenerative medicine aims to replace effete cells in a broad range of conditions associated with damaged cartilage, bone, muscle, tendon and ligament. However the normal process of immune rejection of mismatched allogeneic tissue would appear to prevent the realisation of such ambitions. In fact mesenchymal stem cells avoid allogeneic rejection in humans and in animal models. These finding are supported by in vitro co-culture studies. Three broad mechanisms contribute to this effect. Firstly, mesenchymal stem cells are hypoimmunogenic, often lacking MHC-II and costimulatory molecule expression. Secondly, these stem cells prevent T cell responses indirectly through modulation of dendritic cells and directly by disrupting NK as well as CD8+ and CD4+ T cell function. Thirdly, mesenchymal stem cells induce a suppressive local microenvironment through the production of prostaglandins and interleukin-10 as well as by the expression of indoleamine 2,3,-dioxygenase, which depletes the local milieu of tryptophan. Comparison is made to maternal tolerance of the fetal allograft, and contrasted with the immune evasion mechanisms of tumor cells. Mesenchymal stem cells are a highly regulated self-renewing population of cells with potent mechanisms to avoid allogeneic rejection.

  19. Immunological characteristics of mesenchymal stem cells

    Directory of Open Access Journals (Sweden)

    Cíntia de Vasconcellos Machado

    2013-01-01

    Full Text Available Although bone marrow is the main source, mesenchymal stem cells have already been isolated from various other tissues, such as the liver, pancreas, adipose tissue, peripheral blood and dental pulp. These plastic adherent cells are morphologically similar to fibroblasts and have a high proliferative potential. This special group of cells possesses two essential characteristics: self-renewal and differentiation, with appropriate stimuli, into various cell types. Mesenchymal stem cells are considered immunologically privileged, since they do not express costimulatory molecules, required for complete T cell activation, on their surface. Several studies have shown that these cells exert an immunosuppressive effect on cells from both innate and acquired immunity systems. Mesenchymal stem cells can regulate the immune response in vitro by inhibiting the maturation of dendritic cells, as well as by suppressing the proliferation and function of T and B lymphocytes and natural killer cells. These special properties of mesenchymal stem cells make them a promising strategy in the treatment of immune mediated disorders, such as graft-versus-host disease and autoimmune diseases, as well as in regenerative medicine. The understanding of immune regulation mechanisms of mesenchymal stem cells, and also those involved in the differentiation of these cells in various lineages is primordial for their successful and safe application in different areas of medicine.

  20. [Neural repair].

    Science.gov (United States)

    Kitada, Masaaki; Dezawa, Mari

    2008-05-01

    Recent progress of stem cell biology gives us the hope for neural repair. We have established methods to specifically induce functional Schwann cells and neurons from bone marrow stromal cells (MSCs). The effectiveness of these induced cells was evaluated by grafting them either into peripheral nerve injury, spinal cord injury, or Parkinson' s disease animal models. MSCs-derived Schwann cells supported axonal regeneration and re-constructed myelin to facilitate the functional recovery in peripheral and spinal cord injury. MSCs-derived dopaminergic neurons integrated into host striatum and contributed to behavioral repair. In this review, we introduce the differentiation potential of MSCs and finally discuss about their benefits and drawbacks of these induction systems for cell-based therapy in neuro-traumatic and neuro-degenerative diseases.

  1. Cell delamination in the mesencephalic neural fold and its implication for the origin of ectomesenchyme

    Science.gov (United States)

    Lee, Raymond Teck Ho; Nagai, Hiroki; Nakaya, Yukiko; Sheng, Guojun; Trainor, Paul A.; Weston, James A.; Thiery, Jean Paul

    2013-01-01

    The neural crest is a transient structure unique to vertebrate embryos that gives rise to multiple lineages along the rostrocaudal axis. In cranial regions, neural crest cells are thought to differentiate into chondrocytes, osteocytes, pericytes and stromal cells, which are collectively termed ectomesenchyme derivatives, as well as pigment and neuronal derivatives. There is still no consensus as to whether the neural crest can be classified as a homogenous multipotent population of cells. This unresolved controversy has important implications for the formation of ectomesenchyme and for confirmation of whether the neural fold is compartmentalized into distinct domains, each with a different repertoire of derivatives. Here we report in mouse and chicken that cells in the neural fold delaminate over an extended period from different regions of the cranial neural fold to give rise to cells with distinct fates. Importantly, cells that give rise to ectomesenchyme undergo epithelial-mesenchymal transition from a lateral neural fold domain that does not express definitive neural markers, such as Sox1 and N-cadherin. Additionally, the inference that cells originating from the cranial neural ectoderm have a common origin and cell fate with trunk neural crest cells prompted us to revisit the issue of what defines the neural crest and the origin of the ectomesenchyme. PMID:24198279

  2. Congenital sacral mesenchymal chondrosarcoma in a neonate: A ...

    African Journals Online (AJOL)

    Mesenchymal chondrosarcomas are rare malignant tumours in children, especially, in neonates. The authors present a case of congenital mesenchymal chondrosarcoma in a 1-day neonate located in sacrum. According to the authors' literature searches, this case is the fi rst congenital sacral mesenchymal ...

  3. Epithelial-Mesenchymal Transition and Breast Cancer

    Directory of Open Access Journals (Sweden)

    Yanyuan Wu

    2016-01-01

    Full Text Available Breast cancer is the most common cancer in women and distant site metastasis is the main cause of death in breast cancer patients. There is increasing evidence supporting the role of epithelial-mesenchymal transition (EMT in tumor cell progression, invasion, and metastasis. During the process of EMT, epithelial cancer cells acquire molecular alternations that facilitate the loss of epithelial features and gain of mesenchymal phenotype. Such transformation promotes cancer cell migration and invasion. Moreover, emerging evidence suggests that EMT is associated with the increased enrichment of cancer stem-like cells (CSCs and these CSCs display mesenchymal characteristics that are resistant to chemotherapy and target therapy. However, the clinical relevance of EMT in human cancer is still under debate. This review will provide an overview of current evidence of EMT from studies using clinical human breast cancer tissues and its associated challenges.

  4. Mesenchymal Stem Cells for Osteochondral Tissue Engineering.

    Science.gov (United States)

    Ng, Johnathan; Bernhard, Jonathan; Vunjak-Novakovic, Gordana

    2016-01-01

    Mesenchymal stem cells (MSC) are of major interest in regenerative medicine, as they are easily harvested from a variety of sources (including bone marrow and fat aspirates) and they are able to form a range of mesenchymal tissues, in vitro and in vivo. We focus here on the use of MSCs for engineering of cartilage, bone, and complex osteochondral tissue constructs, using protocols that replicate some aspects of natural mesodermal development. For engineering of human bone, we discuss some of the current advances, and highlight the use of perfusion bioreactors for supporting anatomically exact human bone grafts. For engineering of human cartilage, we discuss the limitations of current approaches, and highlight engineering of stratified, mechanically functional human cartilage interfaced with bone by mesenchymal condensation of MSCs. Taken together, current advances enable engineering of physiologically relevant bone, cartilage and osteochondral composites, and physiologically relevant studies of osteochondral development and disease.

  5. Immortalized mesenchymal stem cells: an alternative to primary mesenchymal stem cells in neuronal differentiation and neuroregeneration associated studies

    Directory of Open Access Journals (Sweden)

    Gong Min

    2011-11-01

    Full Text Available Abstract Background Mesenchymal stem cells (MSCs can be induced to differentiate into neuronal cells under appropriate cellular conditions and transplanted in brain injury and neurodegenerative diseases animal models for neuroregeneration studies. In contrast to the embryonic stem cells (ESCs, MSCs are easily subject to aging and senescence because of their finite ability of self-renewal. MSCs senescence seriously affected theirs application prospects as a promising tool for cell-based regenerative medicine and tissue engineering. In the present study, we established a reversible immortalized mesenchymal stem cells (IMSCs line by using SSR#69 retrovirus expressing simian virus 40 large T (SV40T antigen as an alternative to primary MSCs. Methods The retroviral vector SSR#69 expressing simian virus 40 large T (SV40T antigen was used to construct IMSCs. IMSCs were identified by flow cytometry to detect cell surface makers. To investigate proliferation and differentiation potential of IMSCs, cell growth curve determination and mesodermal trilineage differentiation tests were performed. Neuronal differentiation characteristics of IMSCs were detected in vitro. Before IMSCs transplantation, we excluded its tumorigenicity in nude mice firstly. The Morris water maze tests and shuttle box tests were performed five weeks after HIBD models received cells transplantation therapy. Results In this study, reversible IMSCs were constructed successfully and had the similar morphology and cell surface makers as primary MSCs. IMSCs possessed better ability of proliferation and anti-senescence compared with primary MSCs, while maintained multilineage differentiation capacity. Neural-like cells derived from IMSCs had similar expressions of neural-specific genes, protein expression patterns and resting membrane potential (RMP compared with their counterparts derived from primary MSCs. There was no bump formation in nude mice subcutaneously injected with IMSCs. IMSCs

  6. Epithelial-Mesenchymal Transition in Pancreatic Carcinoma

    Directory of Open Access Journals (Sweden)

    Thomas Wirth

    2010-12-01

    Full Text Available Pancreatic carcinoma is the fourth-leading cause of cancer death and is characterized by early invasion and metastasis. The developmental program of epithelial-mesenchymal transition (EMT is of potential importance for this rapid tumor progression. During EMT, tumor cells lose their epithelial characteristics and gain properties of mesenchymal cells, such as enhanced motility and invasive features. This review will discuss recent findings pertinent to EMT in pancreatic carcinoma. Evidence for and molecular characteristics of EMT in pancreatic carcinoma will be outlined, as well as the connection of EMT to related topics, e.g., cancer stem cells and drug resistance.

  7. Properties of Dental Pulp-derived Mesenchymal Stem Cells and the Effects of Culture Conditions.

    Science.gov (United States)

    Kawashima, Nobuyuki; Noda, Sonoko; Yamamoto, Mioko; Okiji, Takashi

    2017-09-01

    Dental pulp mesenchymal stem cells (DPMSCs) highly express mesenchymal stem cell markers and possess the potential to differentiate into neural cells, osteoblasts, adipocytes, and chondrocytes. Thus, DPMSCs are considered suitable for tissue regeneration. The colony isolation method has commonly been used to collect relatively large amounts of heterogeneous DPMSCs. Homogenous DPMSCs can be isolated by fluorescence-activated cell sorting using antibodies against mesenchymal stem cell markers, although this method yields a limited number of cells. Both quality and quantity of DPMSCs are critical to regenerative therapy, and cell culture methods need to be improved. We thus investigated the properties of DPMSCs cultured with different methods. DPMSCs in a three-dimensional spheroid culture system, which is similar to the hanging drop culture for differentiation of embryonic stem cells, showed upregulation of odonto-/osteoblastic markers and mineralized nodule formation. This suggests that this three-dimensional spheroid culturing system for DPMSCs may be suitable for inducing hard tissues. We further examined the effect of cell culture density on the properties of DPMSCs because the properties of stem cells can be altered depending on the cell density. DPMSCs cultured under the confluent cell density condition showed slight downregulation of some mesenchymal stem cell markers compared with those under the sparse condition. The ability of DPMSCs to differentiate into hard tissue-forming cells was found to be enhanced in the confluent condition, suggesting that the confluent culture condition may not be suitable for maintaining the stemness of DPMSCs. When DPMSCs are to be used for hard tissue regeneration, dense followed by sparse cell culture conditions may be a better alternative strategy. Copyright © 2017 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  8. Functional recovery in acute traumatic spinal cord injury after transplantation of human umbilical cord mesenchymal stem cells.

    Science.gov (United States)

    Hu, Sheng-Li; Luo, Hai-Shui; Li, Jiang-Tao; Xia, Yong-Zhi; Li, Lan; Zhang, Li-Jun; Meng, Hui; Cui, Gao-Yu; Chen, Zhi; Wu, Nan; Lin, Jiang-Kai; Zhu, Gang; Feng, Hua

    2010-11-01

    Spinal cord injury results in loss of neurons, degeneration of axons, formation of glial scar, and severe functional impairment. Human umbilical cord mesenchymal stem cells can be induced to form neural cells in vitro. Thus, these cells have a potential therapeutic role for treating spinal cord injury. Rats were randomly divided into three groups: sham operation group, control group, and human umbilical cord mesenchymal stem cell group. All groups were subjected to spinal cord injury by weight drop device except for sham group. Thirty-six female Sprague-Dawley rats. The control group received Dulbecco's modified essential media/nutrient mixture F-12 injections, whereas the human umbilical cord mesenchymal stem cell group undertook cells transplantation at the dorsal spinal cord 2 mm rostrally and 2 mm caudally to the injury site at 24 hrs after spinal cord injury. Rats from each group were examined for neurologic function and contents of brain-derived neurotrophic factor, glial cell line-derived neurotrophic factor, and neurotrophin-3. Survival, migration, and differentiation of human umbilical cord mesenchymal stem cells, regeneration of axons, and formation of glial scar were also explored by using immunohistochemistry and immunofluorescence. Recovery of hindlimb locomotor function was significantly enhanced in the human umbilical cord mesenchymal stem cells grafted animals at 5 wks after transplantation. This recovery was accompanied by increased length of neurofilament-positive fibers and increased numbers of growth cone-like structures around the lesion site. Transplanted human umbilical cord-mesenchymal stem cells survived, migrated over short distances, and produced large amounts of glial cell line-derived neurotrophic factor and neurotrophin-3 in the host spinal cord. There were fewer reactive astrocytes in both the rostral and caudal stumps of the spinal cord in the human umbilical cord-mesenchymal stem cell group than in the control group. Treatment with

  9. Andrographolide suppresses epithelial mesenchymal transition by ...

    Indian Academy of Sciences (India)

    Epithelial mesenchymal transition (EMT) of lens epithelial cells (LECs) may contribute to the development of posterior capsular opacification (PCO), which leads to visual impairment. Andrographolide has been shown to have therapeutic potential against various cancers. However, its effect on human LECs is still unknown.

  10. Inactivated Mesenchymal Stem Cells Maintain Immunomodulatory Capacity

    NARCIS (Netherlands)

    Luk, Franka; de Witte, Samantha F. H.; Korevaar, Sander S.; Roemeling, Marieke; Franquesa, Marcella; Strini, Tanja; van den Engel, Sandra; Gargesha, Madhusudhana; Roy, Debashish; Dor, Frank J. M. F.; Horwitz, Edwin M.; de Bruin, Ron W. F.; Betjes, Michiel G. H.; Baan, Carla C.; Hoogduijn, Martin J.

    2016-01-01

    Mesenchymal stem cells (MSC) are studied as a cell therapeutic agent for treatment of various immune diseases. However, therapy with living culture-expanded cells comes with safety concerns. Furthermore, development of effective MSC immunotherapy is hampered by lack of knowledge of the mechanisms of

  11. Mesenchymal stem cell-educated macrophages

    NARCIS (Netherlands)

    E. Eggenhofer (Elke); M.J. Hoogduijn (Martin)

    2012-01-01

    textabstractMesenchymal stem cells (MSC) mediate their immunosuppressive effects via a variety of mechanisms. One of these mechanisms involves the induction of macrophages with immunomodulatory capacities. This effect of MSC may be exploited when MSC are used as a cell therapeutic product.

  12. Mesenchymal stem cells in oral reconstructive surgery

    DEFF Research Database (Denmark)

    Jakobsen, C; Sørensen, J A; Kassem, M

    2013-01-01

    This study evaluated clinical outcomes following intraoperative use of adult mesenchymal stem cells (MSCs) in various oral reconstructive procedures. PubMed was searched without language restrictions from 2000 to 2011 using the search words stem cell, oral surgery, tissue engineering, sinus lift...

  13. Enteric neural crest cells regulate vertebrate stomach patterning and differentiation.

    Science.gov (United States)

    Faure, Sandrine; McKey, Jennifer; Sagnol, Sébastien; de Santa Barbara, Pascal

    2015-01-15

    In vertebrates, the digestive tract develops from a uniform structure where reciprocal epithelial-mesenchymal interactions pattern this complex organ into regions with specific morphologies and functions. Concomitant with these early patterning events, the primitive GI tract is colonized by the vagal enteric neural crest cells (vENCCs), a population of cells that will give rise to the enteric nervous system (ENS), the intrinsic innervation of the GI tract. The influence of vENCCs on early patterning and differentiation of the GI tract has never been evaluated. In this study, we report that a crucial number of vENCCs is required for proper chick stomach development, patterning and differentiation. We show that reducing the number of vENCCs by performing vENCC ablations induces sustained activation of the BMP and Notch pathways in the stomach mesenchyme and impairs smooth muscle development. A reduction in vENCCs also leads to the transdifferentiation of the stomach into a stomach-intestinal mixed phenotype. In addition, sustained Notch signaling activity in the stomach mesenchyme phenocopies the defects observed in vENCC-ablated stomachs, indicating that inhibition of the Notch signaling pathway is essential for stomach patterning and differentiation. Finally, we report that a crucial number of vENCCs is also required for maintenance of stomach identity and differentiation through inhibition of the Notch signaling pathway. Altogether, our data reveal that, through the regulation of mesenchyme identity, vENCCs act as a new mediator in the mesenchymal-epithelial interactions that control stomach development. © 2015. Published by The Company of Biologists Ltd.

  14. Introduction to neural networks

    CERN Document Server

    James, Frederick E

    1994-02-02

    1. Introduction and overview of Artificial Neural Networks. 2,3. The Feed-forward Network as an inverse Problem, and results on the computational complexity of network training. 4.Physics applications of neural networks.

  15. Morphological neural networks

    Energy Technology Data Exchange (ETDEWEB)

    Ritter, G.X.; Sussner, P. [Univ. of Florida, Gainesville, FL (United States)

    1996-12-31

    The theory of artificial neural networks has been successfully applied to a wide variety of pattern recognition problems. In this theory, the first step in computing the next state of a neuron or in performing the next layer neural network computation involves the linear operation of multiplying neural values by their synaptic strengths and adding the results. Thresholding usually follows the linear operation in order to provide for nonlinearity of the network. In this paper we introduce a novel class of neural networks, called morphological neural networks, in which the operations of multiplication and addition are replaced by addition and maximum (or minimum), respectively. By taking the maximum (or minimum) of sums instead of the sum of products, morphological network computation is nonlinear before thresholding. As a consequence, the properties of morphological neural networks are drastically different than those of traditional neural network models. In this paper we consider some of these differences and provide some particular examples of morphological neural network.

  16. An extraordinary case of mesenchymal chondrosarcoma metastasis in the thyroid.

    Science.gov (United States)

    Ortiz, Santiago; Tortosa, Francisco; Sobrinho Simões, Manuel

    2015-03-01

    Secondary tumours of the thyroid gland account for 1.25 to 3 % in clinical series and reach 24 % in autopsy series. Chondrosarcoma is a rare malignant mesenchymal tumour of chondrogenic nature; the mesenchymal variant represents less than 3 % of all chondrosarcomas, being therefore extremely rare. A mesenchymal chondrosarcoma metastasis in the thyroid is exceptional; to our knowledge, only three previous cases of chondrosarcoma metastasis in the thyroid have been reported to date but none of such cases corresponded to a mesenchymal chondrosarcoma. We present the first of such a case in a 27-year-old woman with a 4-year history of mesenchymal chondrosarcoma of the sacrum that was treated by surgery and chemotherapy. At the present admission, head and neck computed tomography revealed a well-defined nodule in the thyroid gland. The diagnosis of metastasis from the mesenchymal chondrosarcoma was made in the right lobectomy specimen.

  17. Mesenchymal change and drug resistance in neuroblastoma.

    Science.gov (United States)

    Naiditch, Jessica A; Jie, Chunfa; Lautz, Timothy B; Yu, Songtao; Clark, Sandra; Voronov, Dimitry; Chu, Fei; Madonna, Mary Beth

    2015-01-01

    Metastatic initiation has many phenotypic similarities to epithelial-to-mesenchymal transition, including loss of cell-cell adhesion, increased invasiveness, and increased cell mobility. We have previously demonstrated that drug resistance is associated with a metastatic phenotype in neuroblastoma (NB). The purpose of this project was to determine if the development of doxorubicin resistance is associated with characteristics of mesenchymal change in human NB cells. Total RNA was isolated from wild type (WT) and doxorubicin-resistant (DoxR) human NB cell lines (SK-N-SH and SK-N-BE(2)C) and analyzed using the Illumina Human HT-12 version 4 Expression BeadChip. Differentially expressed genes (DEGs) were identified. Volcano plots and heat maps were generated. Genes of interest with a fold change in expression >1.5 and an adjusted P change via multiple pathways in the transition to a drug-resistant state. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Mesenchymal stromal cells: misconceptions and evolving concepts.

    Science.gov (United States)

    Phinney, Donald G; Sensebé, Luc

    2013-02-01

    Nearly half a century has passed since the publication of the first articles describing plastic-adherent cells from bone marrow, referred to initially as colony-forming unit fibroblasts, then marrow stromal cells, mesenchymal stem cells and most recently multipotent mesenchymal stromal cells (MSCs). As expected, our understanding of the nature and biologic functions of MSCs has undergone major paradigm shifts over this time. Despite significant advances made in deciphering their complex biology and therapeutic potential in both experimental animal models and human clinical trials, numerous misconceptions regarding the nature and function of MSCs have persisted in the field. Continued propagation of these misconceptions in some cases may significantly impede the advancement of MSC-based therapies in clinical medicine. We have identified six prevalent misconceptions about MSCs that we believe affect the field, and we attempt to rectify them based on current available data. Copyright © 2013 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  19. Mesenchymal dental stem cells in regenerative dentistry

    OpenAIRE

    Rodríguez Lozano, Francisco Javier; Insausti, Carmen Luisa; Iniesta, Francisca; Blanquer, Miguel; Ramírez, María del Carmen; Meseguer, Luis; Meseguer Henarejos, Ana Belén; Marín Atucha, Noemi Teresa; Martínez, Salvador; Moraleda Jiménez, José María

    2012-01-01

    In the last decade, tissue engineering is a field that has been suffering an enormous expansion in the regenerative medicine and dentistry. The use of cells as mesenchymal dental stem cells of easy access for dentist and oral surgeon, immunosuppressive properties, high proliferation and capacity to differentiate into odontoblasts, cementoblasts, osteoblasts and other cells implicated in the teeth, suppose a good perspective of future in the clinical dentistry. However, is necessary advance in...

  20. [Mesenchymal gastric tumor--not always GIST].

    Science.gov (United States)

    Grosse-Holz, M; Sackmann, M; Seitz, G

    2015-02-01

    The correct histopathological classification of a gastric mesenchymal tumor as a schwannoma is essential because in contrast to gastrointestinal stromal tumors (GIST) it is a definitive benign neoplasm which can be sufficiently treated by in sano (R0) resection. A (partial) gastrectomy is unnecessary. A clear radiological or sonographical differentiation between a schwannoma and GIST is not possible. The histomorphological and immunohistochemical features of this tumor entity are described.

  1. Human pluripotent stem cell-derived neural constructs for predicting neural toxicity.

    Science.gov (United States)

    Schwartz, Michael P; Hou, Zhonggang; Propson, Nicholas E; Zhang, Jue; Engstrom, Collin J; Santos Costa, Vitor; Jiang, Peng; Nguyen, Bao Kim; Bolin, Jennifer M; Daly, William; Wang, Yu; Stewart, Ron; Page, C David; Murphy, William L; Thomson, James A

    2015-10-06

    Human pluripotent stem cell-based in vitro models that reflect human physiology have the potential to reduce the number of drug failures in clinical trials and offer a cost-effective approach for assessing chemical safety. Here, human embryonic stem (ES) cell-derived neural progenitor cells, endothelial cells, mesenchymal stem cells, and microglia/macrophage precursors were combined on chemically defined polyethylene glycol hydrogels and cultured in serum-free medium to model cellular interactions within the developing brain. The precursors self-assembled into 3D neural constructs with diverse neuronal and glial populations, interconnected vascular networks, and ramified microglia. Replicate constructs were reproducible by RNA sequencing (RNA-Seq) and expressed neurogenesis, vasculature development, and microglia genes. Linear support vector machines were used to construct a predictive model from RNA-Seq data for 240 neural constructs treated with 34 toxic and 26 nontoxic chemicals. The predictive model was evaluated using two standard hold-out testing methods: a nearly unbiased leave-one-out cross-validation for the 60 training compounds and an unbiased blinded trial using a single hold-out set of 10 additional chemicals. The linear support vector produced an estimate for future data of 0.91 in the cross-validation experiment and correctly classified 9 of 10 chemicals in the blinded trial.

  2. Multilineage potential of stable human mesenchymal stem cell line derived from fetal marrow.

    Directory of Open Access Journals (Sweden)

    Atsushi Nagai

    Full Text Available Human bone marrow contains two major cell types, hematopoietic stem cells (HSCs and mesenchymal stem cells (MSCs. MSCs possess self-renewal capacity and pluripotency defined by their ability to differentiate into osteoblasts, chondrocytes, adipocytes and muscle cells. MSCs are also known to differentiate into neurons and glial cells in vitro, and in vivo following transplantation into the brain of animal models of neurological disorders including ischemia and intracerebral hemorrhage (ICH stroke. In order to obtain sufficient number and homogeneous population of human MSCs, we have clonally isolated permanent and stable human MSC lines by transfecting primary cell cultures of fetal human bone marrow MSCs with a retroviral vector encoding v-myc gene. One of the cell lines, HM3.B10 (B10, was found to differentiate into neural cell types including neural stem cells, neurons, astrocytes and oligodendrocytes in vitro as shown by expression of genetic markers for neural stem cells (nestin and Musashi1, neurons (neurofilament protein, synapsin and MAP2, astrocytes (glial fibrillary acidic protein, GFAP and oligodendrocytes (myelin basic protein, MBP as determined by RT-PCR assay. In addition, B10 cells were found to differentiate into neural cell types as shown by immunocytochical demonstration of nestin (for neural stem cells, neurofilament protein and beta-tubulin III (neurons GFAP (astrocytes, and galactocerebroside (oligodendrocytes. Following brain transplantation in mouse ICH stroke model, B10 human MSCs integrate into host brain, survive, differentiate into neurons and astrocytes and induce behavioral improvement in the ICH animals. B10 human MSC cell line is not only a useful tool for the studies of organogenesis and specifically for the neurogenesis, but also provides a valuable source of cells for cell therapy studies in animal models of stroke and other neurological disorders.

  3. Regional differences in the expression of laminin isoforms during mouse neural tube development

    Science.gov (United States)

    Copp, Andrew J.; Carvalho, Rita; Wallace, Adam; Sorokin, Lydia; Sasaki, Takako; Greene, Nicholas D.E.; Ybot-Gonzalez, Patricia

    2013-01-01

    Many significant human birth defects originate around the time of neural tube closure or early during post-closure nervous system development. For example, failure of the neural tube to close generates anencephaly and spina bifida, faulty cell cycle progression is implicated in primary microcephaly, while defective migration of neuroblasts can lead to neuronal migration disorders such as lissencephaly. At the stage of neural tube closure, basement membranes are becoming organised around the neuroepithelium, and beneath the adjacent non-neural surface ectoderm. While there is circumstantial evidence to implicate basement membrane dynamics in neural tube and surface ectodermal development, we have an incomplete understanding of the molecular composition of basement membranes at this stage. In the present study, we examined the developing basement membranes of the mouse embryo at mid-gestation (embryonic day 9.5), with particular reference to laminin composition. We performed in situ hybridization to detect the mRNAs of all eleven individual laminin chains, and immunohistochemistry to identify which laminin chains are present in the basement membranes. From this information, we inferred the likely laminin variants and their tissues of origin: that is, whether a given basement membrane laminin is contributed by epithelium, mesenchyme, or both. Our findings reveal major differences in basement composition along the body axis, with the rostral neural tube (at mandibular arch and heart levels) exhibiting many distinct laminin variants, while the lumbar level where the neural tube is just closing shows a much simpler laminin profile. Moreover, there appears to be a marked difference in the extent to which the mesenchyme contributes laminin variants to the basement membrane, with potential contribution of several laminins rostrally, but no contribution caudally. This information paves the way towards a mechanistic analysis of basement membrane laminin function during early

  4. Improvement of renal function after human umbilical cord mesenchymal stem cell treatment on chronic renal failure and thoracic spinal cord entrapment: a case report.

    Science.gov (United States)

    Rahyussalim, Ahmad Jabir; Saleh, Ifran; Kurniawati, Tri; Lutfi, Andi Praja Wira Yudha

    2017-11-30

    Chronic renal failure is an important clinical problem with significant socioeconomic impact worldwide. Thoracic spinal cord entrapment induced by a metabolic yield deposit in patients with renal failure results in intrusion of nervous tissue and consequently loss of motor and sensory function. Human umbilical cord mesenchymal stem cells are immune naïve and they are able to differentiate into other phenotypes, including the neural lineage. Over the past decade, advances in the field of regenerative medicine allowed development of cell therapies suitable for kidney repair. Mesenchymal stem cell studies in animal models of chronic renal failure have uncovered a unique potential of these cells for improving function and regenerating the damaged kidney. We report a case of a 62-year-old ethnic Indonesian woman previously diagnosed as having thoracic spinal cord entrapment with paraplegic condition and chronic renal failure on hemodialysis. She had diabetes mellitus that affected her kidneys and had chronic renal failure for 2 years, with creatinine level of 11 mg/dl, and no urinating since then. She was treated with human umbilical cord mesenchymal stem cell implantation protocol. This protocol consists of implantation of 16 million human umbilical cord mesenchymal stem cells intrathecally and 16 million human umbilical cord mesenchymal stem cells intravenously. Three weeks after first intrathecal and intravenous implantation she could move her toes and her kidney improved. Her creatinine level decreased to 9 mg/dl. Now after 8 months she can raise her legs and her creatinine level is 2 mg/dl with normal urinating. Human umbilical cord mesenchymal stem cell implantations led to significant improvement for spinal cord entrapment and kidney failure. The major histocompatibility in allogeneic implantation is an important issue to be addressed in the future.

  5. Evolvable Neural Software System

    Science.gov (United States)

    Curtis, Steven A.

    2009-01-01

    The Evolvable Neural Software System (ENSS) is composed of sets of Neural Basis Functions (NBFs), which can be totally autonomously created and removed according to the changing needs and requirements of the software system. The resulting structure is both hierarchical and self-similar in that a given set of NBFs may have a ruler NBF, which in turn communicates with other sets of NBFs. These sets of NBFs may function as nodes to a ruler node, which are also NBF constructs. In this manner, the synthetic neural system can exhibit the complexity, three-dimensional connectivity, and adaptability of biological neural systems. An added advantage of ENSS over a natural neural system is its ability to modify its core genetic code in response to environmental changes as reflected in needs and requirements. The neural system is fully adaptive and evolvable and is trainable before release. It continues to rewire itself while on the job. The NBF is a unique, bilevel intelligence neural system composed of a higher-level heuristic neural system (HNS) and a lower-level, autonomic neural system (ANS). Taken together, the HNS and the ANS give each NBF the complete capabilities of a biological neural system to match sensory inputs to actions. Another feature of the NBF is the Evolvable Neural Interface (ENI), which links the HNS and ANS. The ENI solves the interface problem between these two systems by actively adapting and evolving from a primitive initial state (a Neural Thread) to a complicated, operational ENI and successfully adapting to a training sequence of sensory input. This simulates the adaptation of a biological neural system in a developmental phase. Within the greater multi-NBF and multi-node ENSS, self-similar ENI s provide the basis for inter-NBF and inter-node connectivity.

  6. Molecular dissection of mesenchymal-epithelial interactions in the hair follicle.

    Directory of Open Access Journals (Sweden)

    2005-11-01

    Full Text Available De novo hair follicle formation in embryonic skin and new hair growth in adult skin are initiated when specialized mesenchymal dermal papilla (DP cells send cues to multipotent epithelial stem cells. Subsequently, DP cells are enveloped by epithelial stem cell progeny and other cell types to form a niche orchestrating hair growth. Understanding the general biological principles that govern the mesenchymal-epithelial interactions within the DP niche, however, has been hampered so far by the lack of systematic approaches to dissect the complete molecular make-up of this complex tissue. Here, we take a novel multicolor labeling approach, using cell type-specific transgenic expression of red and green fluorescent proteins in combination with immunolabeling of specific antigens, to isolate pure populations of DP and four of its surrounding cell types: dermal fibroblasts, melanocytes, and two different populations of epithelial progenitors (matrix and outer root sheath cells. By defining their transcriptional profiles, we develop molecular signatures characteristic for the DP and its niche. Validating the functional importance of these signatures is a group of genes linked to hair disorders that have been largely unexplored. Additionally, the DP signature reveals novel signaling and transcription regulators that distinguish them from other cell types. The mesenchymal-epithelial signatures include key factors previously implicated in ectodermal-neural fate determination, as well as a myriad of regulators of bone morphogenetic protein signaling. These findings establish a foundation for future functional analyses of the roles of these genes in hair development. Overall, our strategy illustrates how knowledge of the genes uniquely expressed by each cell type residing in a complex niche can reveal important new insights into the biology of the tissue and its associated disease states.

  7. Neuroblastoma cells injected into experimental mature teratoma reveal a tropism for embryonic loose mesenchyme.

    Science.gov (United States)

    Jamil, S; Cedervall, J; Hultman, I; Ali, R; Margaryan, N V; Rasmuson, A; Johnsen, J I; Sveinbjörnsson, B; Dalianis, T; Kanter, L; Orrego, A; Strizzi, L; Hendrix, M J C; Sandstedt, B; Kogner, P; Ahrlund-Richter, L

    2013-09-01

    Embryonic neural tumors are responsible for a disproportionate number of cancer deaths in children. Although dramatic improvements in survival for pediatric malignancy has been achieved in previous years advancements seem to be slowing down. For the development of new enhanced therapy and an increased understanding of the disease, pre-clinical models better capturing the neoplastic niche are essential. Tumors of early childhood present in this respect a particular challenge. Here, we explore how components of the embryonic process in stem‑cell induced mature teratoma can function as an experimental in vivo microenvironment instigating the growth of injected childhood neuroblastoma (NB) cell lines. Three human NB cell lines, IMR-32, Kelly and SK-N-BE(2), were injected into mature pluripotent stem cell‑induced teratoma (PSCT) and compared to xenografts of the same cell lines. Proliferative NB cells from all lines were readily detected in both models with a typical histology of a poorly differentiated NB tumor with a variable amount of fibrovascular stroma. Uniquely in the PSCT microenvironment, NB cells were found integrated in a non‑random fashion. Neuroblastoma cells were never observed in areas with well-differentiated somatic tissue i.e. bone, muscle, gut or areas of other easily identifiable tissue types. Instead, the three cell lines all showed initial growth exclusively occurring in the embryonic loose mesenchymal stroma, resulting in a histology recapitulating NB native presentation in vivo. Whether this reflects the 'open' nature of loose mesenchyme more easily giving space to new cells compared to other more dense tissues, the rigidity of matrix providing physical cues modulating NB characteristics, or if embryonic loose mesenchyme may supply developmental cues that attracted or promoted the integration of NB, remains to be tested. We tentatively hypothesize that mature PSCT provide an embryonic niche well suited for in vivo studies on NB.

  8. FoxD3 deficiency promotes breast cancer progression by induction of epithelial–mesenchymal transition

    Energy Technology Data Exchange (ETDEWEB)

    Chu, Tian-Li [Department of General Surgery, The People’s Hospital of Wuqing, Tianjin (China); Zhao, Hong-Meng [Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Breast Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Li, Yue [Department of Respiration, Affiliated Hospital of Medical College of Chinese People’s Armed Police Force, Tianjin (China); Chen, Ao-Xiang; Sun, Xuan [Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Breast Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Ge, Jie, E-mail: gejie198003@163.com [Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Breast Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China)

    2014-04-04

    Highlights: • FOXD3 is down-regulated in breast cancer tissues. • FOXD3 inhibits breast cancer cell proliferation and invasion. • FoxD3 deficiency induces epithelial–mesenchymal transition. - Abstract: The transcription factor forkhead box D3 (FOXD3) plays an important role in the development of neural crest and gastric cancer cells. However, the function and mechanisms of FOXD3 in the breast tumorigenesis and progression is still limited. Here, we report that FOXD3 is a tumor suppressor of breast cancer tumorigenicity and aggressiveness. We found that FOXD3 is down-regulated in breast cancer tissues. Patients with low FOXD3 expression have a poor outcome. Depletion of FOXD3 expression promotes breast cancer cell proliferation and invasion in vitro, whereas overexpression of FOXD3 inhibits breast cancer cell proliferation and invasion both in vitro and in vivo. In addition, depletion of FOXD3 is linked to epithelial–mesenchymal transition (EMT)-like phenotype. Our results indicate FOXD3 exhibits tumor suppressive activity and may be useful for breast therapy.

  9. Possible mechanism of disintegrin/like domain in mesenchymal ...

    African Journals Online (AJOL)

    Liver disease is one of the major health problems in many countries. Mesenchymal Stem cells have opened a new approach to deal with liver fibrosis. Improvement of bone marrow derived mesenchymal stem cellshoming after systemic injection of disintegrin/like domain purified from Egyptian horned Cerastes cerastes ...

  10. Enhanced neuro-therapeutic potential of Wharton's Jelly-derived mesenchymal stem cells in comparison with bone marrow mesenchymal stem cells culture.

    Science.gov (United States)

    Drela, Katarzyna; Lech, Wioletta; Figiel-Dabrowska, Anna; Zychowicz, Marzena; Mikula, Michał; Sarnowska, Anna; Domanska-Janik, Krystyna

    2016-04-01

    Substantial inconsistencies in mesenchymal stem (stromal) cell (MSC) therapy reported in early translational and clinical studies may indicate need for selection of the proper cell population for any particular therapeutic purpose. In the present study we have examined stromal stem cells derived either from umbilical cord Wharton's Jelly (WJ-MSC) or bone marrow (BM-MSC) of adult, healthy donors. The cells characterized in accordance with the International Society for Cellular Therapy (ISCT) indications as well as other phenotypic and functional parameters have been compared under strictly controlled culture conditions. WJ-MSC, in comparison with BM-MSC, exhibited a higher proliferation rate, a greater expansion capability being additionally stimulated under low-oxygen atmosphere, enhanced neurotrophic factors gene expression and spontaneous tendency toward a neural lineage differentiation commitment confirmed by protein and gene marker induction. Our data suggest that WJ-MSC may represent an example of immature-type "pre-MSC," where a substantial cellular component is embryonic-like, pluripotent derivatives with the default neural-like differentiation. These cells may contribute in different extents to nearly all classical MSC populations adversely correlated with the age of cell donors. Our data suggest that neuro-epithelial markers, like nestin, stage specific embryonic antigens-4 or α-smooth muscle actin expressions, may serve as useful indicators of MSC culture neuro-regeneration-associated potency. Copyright © 2016 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  11. Hyaluronan-mediated aggregation of limb bud mesenchyme and mesenchymal condensation during chondrogenesis.

    Science.gov (United States)

    Maleski, M P; Knudson, C B

    1996-05-25

    Cell condensations are the initial structures in the formation of proper cartilage and skeletal patterning in the developing vertebrate limb. Chondrogenic differentiation is dependent upon the cell-cell and/or cell-matrix interactions which take place during the condensation process. Coincident with the onset of condensation is the expression by limb mesenchyme of specific cell surface binding sites for the extracellular matrix macromolecule hyaluronan. The association of hyaluronan with the cell surface can influence the behavior of cells, especially cell aggregation. In this study the possible involvement of hyaluronan as an extracellular linker molecule in the cell-cell adhesion event during mesenchymal condensation was investigated in the avian limb model. Hyaluronan hexasaccharides were used to prevent the multivalent interactions that occur between native hyaluronan macromolecules and the cell surface. Our studies show that hyaluronan is required for early adhesive cell-cell interactions of limb bud mesenchyme and that perturbations of hyaluronan-cell interactions with hyaluronan hexasaccharides result in a delay in the formation of condensations as well as a delay in chondrogenic differentiation of mesenchymal cells in micromass cultures.

  12. Consciousness and neural plasticity

    DEFF Research Database (Denmark)

    In contemporary consciousness studies the phenomenon of neural plasticity has received little attention despite the fact that neural plasticity is of still increased interest in neuroscience. We will, however, argue that neural plasticity could be of great importance to consciousness studies....... If consciousness is related to neural processes it seems, at least prima facie, that the ability of the neural structures to change should be reflected in a theory of this relationship "Neural plasticity" refers to the fact that the brain can change due to its own activity. The brain is not static but rather...... a dynamic entity, which physical structure changes according to its use and environment. This change may take the form of growth of new neurons, the creation of new networks and structures, and change within network structures, that is, changes in synaptic strengths. Plasticity raises questions about...

  13. Fuzzy and neural control

    Science.gov (United States)

    Berenji, Hamid R.

    1992-01-01

    Fuzzy logic and neural networks provide new methods for designing control systems. Fuzzy logic controllers do not require a complete analytical model of a dynamic system and can provide knowledge-based heuristic controllers for ill-defined and complex systems. Neural networks can be used for learning control. In this chapter, we discuss hybrid methods using fuzzy logic and neural networks which can start with an approximate control knowledge base and refine it through reinforcement learning.

  14. What Is Neural Plasticity?

    Science.gov (United States)

    von Bernhardi, Rommy; Bernhardi, Laura Eugenín-von; Eugenín, Jaime

    2017-01-01

    "Neural plasticity" refers to the capacity of the nervous system to modify itself, functionally and structurally, in response to experience and injury. As the various chapters in this volume show, plasticity is a key component of neural development and normal functioning of the nervous system, as well as a response to the changing environment, aging, or pathological insult. This chapter discusses how plasticity is necessary not only for neural networks to acquire new functional properties, but also for them to remain robust and stable. The article also reviews the seminal proposals developed over the years that have driven experiments and strongly influenced concepts of neural plasticity.

  15. Neural Systems Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — As part of the Electrical and Computer Engineering Department and The Institute for System Research, the Neural Systems Laboratory studies the functionality of the...

  16. A neural flow estimator

    DEFF Research Database (Denmark)

    Jørgensen, Ivan Harald Holger; Bogason, Gudmundur; Bruun, Erik

    1995-01-01

    is implemented using switched-current technique and is capable of estimating flow in the μl/s range. The neural estimator is built around a multiplierless neural network, containing 96 synaptic weights which are updated using the LMS1-algorithm. An experimental chip has been designed that operates at 5 V......This paper proposes a new way to estimate the flow in a micromechanical flow channel. A neural network is used to estimate the delay of random temperature fluctuations induced in a fluid. The design and implementation of a hardware efficient neural flow estimator is described. The system...

  17. Mesenchymal Stem Cells in Fibrotic Disease.

    Science.gov (United States)

    El Agha, Elie; Kramann, Rafael; Schneider, Rebekka K; Li, Xiaokun; Seeger, Werner; Humphreys, Benjamin D; Bellusci, Saverio

    2017-08-03

    Fibrosis is associated with organ failure and high mortality and is commonly characterized by aberrant myofibroblast accumulation. Investigating the cellular origin of myofibroblasts in various diseases is thus a promising strategy for developing targeted anti-fibrotic treatments. Recent studies using genetic lineage tracing technology have implicated diverse organ-resident perivascular mesenchymal stem cell (MSC)-like cells and bone marrow-MSCs in myofibroblast generation during fibrosis development. In this Review, we give an overview of the emerging role of MSCs and MSC-like cells in myofibroblast-mediated fibrotic disease in the kidney, lung, heart, liver, skin, and bone marrow. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Mesenchymal Stem Cell Therapy for Nerve Regeneration and Immunomodulation after Composite Tissue Allotransplantation

    Science.gov (United States)

    2012-02-01

    10-1-0927 TITLE: Mesenchymal Stem Cell Therapy for Nerve Regeneration and Immunomodulation after Composite Tissue Allotransplantation...immunosuppression. Bone Marrow Derived Mesenchymal stem cells (BM-MSCs) are pluripotent cells, capable of differentiation along multiple mesenchymal lineages into...As part of implemented transition from University of Pittsburgh to Johns Hopkins University, we optimized our mesenchymal stem cell (MSC) isolation

  19. Applicability of tooth derived stem cells in neural regeneration

    Directory of Open Access Journals (Sweden)

    Ludovica Parisi

    2016-01-01

    Full Text Available Within the nervous system, regeneration is limited, and this is due to the small amount of neural stem cells, the inhibitory origin of the stem cell niche and often to the development of a scar which constitutes a mechanical barrier for the regeneration. Regarding these aspects, many efforts have been done in the research of a cell component that combined with scaffolds and growth factors could be suitable for nervous regeneration in regenerative medicine approaches. Autologous mesenchymal stem cells represent nowadays the ideal candidate for this aim, thank to their multipotency and to their amount inside adult tissues. However, issues in their harvesting, through the use of invasive techniques, and problems involved in their ageing, require the research of new autologous sources. To this purpose, the recent discovery of a stem cells component in teeth, and which derive from neural crest cells, has came to the light the possibility of using dental stem cells in nervous system regeneration. In this work, in order to give guidelines on the use of dental stem cells for neural regeneration, we briefly introduce the concepts of regeneration and regenerative medicine, we then focus the attention on odontogenesis, which involves the formation and the presence of a stem component in different parts of teeth, and finally we describe some experimental approaches which are exploiting dental stem cells for neural studies.

  20. Applicability of tooth derived stem cells in neural regeneration.

    Science.gov (United States)

    Parisi, Ludovica; Manfredi, Edoardo

    2016-11-01

    Within the nervous system, regeneration is limited, and this is due to the small amount of neural stem cells, the inhibitory origin of the stem cell niche and often to the development of a scar which constitutes a mechanical barrier for the regeneration. Regarding these aspects, many efforts have been done in the research of a cell component that combined with scaffolds and growth factors could be suitable for nervous regeneration in regenerative medicine approaches. Autologous mesenchymal stem cells represent nowadays the ideal candidate for this aim, thank to their multipotency and to their amount inside adult tissues. However, issues in their harvesting, through the use of invasive techniques, and problems involved in their ageing, require the research of new autologous sources. To this purpose, the recent discovery of a stem cells component in teeth, and which derive from neural crest cells, has came to the light the possibility of using dental stem cells in nervous system regeneration. In this work, in order to give guidelines on the use of dental stem cells for neural regeneration, we briefly introduce the concepts of regeneration and regenerative medicine, we then focus the attention on odontogenesis, which involves the formation and the presence of a stem component in different parts of teeth, and finally we describe some experimental approaches which are exploiting dental stem cells for neural studies.

  1. Molecular and cellular changes associated with the evolution of novel jaw muscles in parrots.

    Science.gov (United States)

    Tokita, Masayoshi; Nakayama, Tomoki; Schneider, Richard A; Agata, Kiyokazu

    2013-02-07

    Vertebrates have achieved great evolutionary success due in large part to the anatomical diversification of their jaw complex, which allows them to inhabit almost every ecological niche. While many studies have focused on mechanisms that pattern the jaw skeleton, much remains to be understood about the origins of novelty and diversity in the closely associated musculature. To address this issue, we focused on parrots, which have acquired two anatomically unique jaw muscles: the ethmomandibular and the pseudomasseter. In parrot embryos, we observe distinct and highly derived expression patterns for Scx, Bmp4, Tgfβ2 and Six2 in neural crest-derived mesenchyme destined to form jaw muscle connective tissues. Furthermore, immunohistochemical analysis reveals that cell proliferation is more active in the cells within the jaw muscle than in surrounding connective tissue cells. This biased and differentially regulated mode of cell proliferation in cranial musculoskeletal tissues may allow these unusual jaw muscles to extend towards their new attachment sites. We conclude that the alteration of neural crest-derived connective tissue distribution during development may underlie the spatial changes in jaw musculoskeletal architecture found only in parrots. Thus, parrots provide valuable insights into molecular and cellular mechanisms that may generate evolutionary novelties with functionally adaptive significance.

  2. Neural Networks: Implementations and Applications

    NARCIS (Netherlands)

    Vonk, E.; Veelenturf, L.P.J.; Jain, L.C.

    1996-01-01

    Artificial neural networks, also called neural networks, have been used successfully in many fields including engineering, science and business. This paper presents the implementation of several neural network simulators and their applications in character recognition and other engineering areas

  3. ML327 induces apoptosis and sensitizes Ewing sarcoma cells to TNF-related apoptosis-inducing ligand.

    Science.gov (United States)

    Rellinger, Eric J; Padmanabhan, Chandrasekhar; Qiao, Jingbo; Appert, Andrew; Waterson, Alex G; Lindsley, Craig W; Beauchamp, R Daniel; Chung, Dai H

    2017-09-16

    Ewing sarcomas are rare mesenchymal-derived bone and soft tissue tumors in children. Afflicted children with distant metastases have poor survival despite aggressive therapeutics. Epithelial-to-mesenchymal transition in epithelial carcinomas is associated with loss of E-cadherin and resistance to apoptosis. ML327 is a novel small molecule that we have previously shown to reverse epithelial-to-mesenchymal transition features in both epithelial and neural crest-derived cancers. Herein, we sought to evaluate the effects of ML327 on mesenchymal-derived Ewing sarcoma cells, hypothesizing that ML327 initiates growth arrest and sensitizes to TNF-related apoptosis-inducing ligand. ML327 induced protein expression changes, increased E-cadherin and decreased vimentin, consistent with partial induction of mesenchymal-to-epithelial transition in multiple Ewing Sarcoma cell lines (SK-N-MC, TC71, and ES-5838). Induction of epithelial features was associated with apoptosis, as demonstrated by PARP and Caspase 3 cleavage by immunoblotting. Cell cycle analysis validated these findings by marked induction of the subG0 cell population. In vitro combination treatment with TRAIL demonstrated additive induction of apoptotic markers. Taken together, these findings establish a rationale for further in vivo trials of ML327 in cells of mesenchymal origin both alone and in combination with TRAIL. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Anterior Hox Genes Interact with Components of the Neural Crest Specification Network to Induce Neural Crest Fates

    Science.gov (United States)

    Gouti, Mina; Briscoe, James; Gavalas, Anthony

    2011-01-01

    Hox genes play a central role in neural crest (NC) patterning particularly in the cranial region of the body. Despite evidence that simultaneous loss of Hoxa1 and Hoxb1 function resulted in NC specification defects, the role of Hox genes in NC specification has remained unclear due to extended genetic redundancy among Hox genes. To circumvent this problem, we expressed anterior Hox genes in the trunk neural tube of the developing chick embryo. This demonstrated that anterior Hox genes play a central role in NC cell specification by rapidly inducing the key transcription factors Snail2 and Msx1/2 and a neural progenitor to NC cell fate switch characterized by cell adhesion changes and an epithelial-to-mesenchymal transition (EMT). Cells delaminated from dorsal and medial neural tube levels and generated ectopic neurons, glia progenitors, and melanocytes. The mobilization of the NC genetic cascade was dependent upon bone morphogenetic protein signaling and optimal levels of Notch signaling. Therefore, anterior Hox patterning genes participate in NC specification and EMT by interacting with NC-inducing signaling pathways and regulating the expression of key genes involved in these processes. Stem Cells 2011;29:858–870 PMID:21433221

  5. Critical Branching Neural Networks

    Science.gov (United States)

    Kello, Christopher T.

    2013-01-01

    It is now well-established that intrinsic variations in human neural and behavioral activity tend to exhibit scaling laws in their fluctuations and distributions. The meaning of these scaling laws is an ongoing matter of debate between isolable causes versus pervasive causes. A spiking neural network model is presented that self-tunes to critical…

  6. Kunstige neurale net

    DEFF Research Database (Denmark)

    Hørning, Annette

    1994-01-01

    Artiklen beskæftiger sig med muligheden for at anvende kunstige neurale net i forbindelse med datamatisk procession af naturligt sprog, specielt automatisk talegenkendelse.......Artiklen beskæftiger sig med muligheden for at anvende kunstige neurale net i forbindelse med datamatisk procession af naturligt sprog, specielt automatisk talegenkendelse....

  7. Mesenchymal stromal cells in myeloid malignancies.

    Science.gov (United States)

    Schroeder, Thomas; Geyh, Stefanie; Germing, Ulrich; Haas, Rainer

    2016-12-01

    Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are clonal myeloid disorders characterized by hematopoietic insufficiency. As MDS and AML are considered to originate from genetic and molecular defects of hematopoietic stem and progenitor cells (HSPC), the main focus of research in this field has focused on the characterization of these cells. Recently, the contribution of BM microenvironment to the pathogenesis of myeloid malignancies, in particular MDS and AML has gained more interest. This is based on a better understanding of its physiological role in the regulation of hematopoiesis. Additionally, it was demonstrated as a 'proof of principle' that genetic disruption of cells of the mesenchymal or osteoblastic lineage can induce MDS, MPS or AML in mice. In this review, we summarize the current knowledge about the contribution of the BM microenvironment, in particular mesenchymal stromal cells (MSC) to the pathogenesis of AML and MDS. Furthermore, potential models integrating the BM microenvironment into the pathophysiology of these myeloid disorders are discussed. Finally, strategies to therapeutically exploit this knowledge and to interfere with the crosstalk between clonal hematopoietic cells and altered stem cell niches are introduced.

  8. Placental Mesenchymal Dysplasia: A Case Report

    Directory of Open Access Journals (Sweden)

    Rachna Agarwal

    2012-01-01

    Full Text Available Introduction. A rare case of histologically proven placental mesenchymal dysplasia (PMD with fetal omphalocele in a 22-year-old patient is reported. Material and Methods. Antenatal ultrasound of this patient showed hydropic placenta with a live fetus of 17 weeks period of gestation associated with omphalocele. Cordocentesis detected the diploid karyotype of the fetus. Patient, when prognosticated, choose to terminate the pregnancy in view of high incidence of fetal and placental anomalies. Subsequent histopathological examination of placenta established the diagnosis to be placental mesenchymal dysplasia. Conclusion. On clinical and ultrasonic grounds, suspicion of P.M.D. arises when hydropic placenta with a live fetus presents in second trimester of pregnancy. Cordocentesis can detect the diploid karyotype of the fetus in such cases. As this condition is prognostically better than triploid partial mole, continuation of pregnancy can sometimes be considered after through antenatal screening and patient counseling. However, a definite diagnosis of P.M.D. is made only on placental histology by absence of trophoblast hyperplasia and trophoblastic inclusions.

  9. Mesenchymal stromal cell therapy in ischemic stroke

    Directory of Open Access Journals (Sweden)

    Zhang Y

    2016-11-01

    Full Text Available Ye Zhang, Hong Deng, Chao Pan, Yang Hu, Qian Wu, Na Liu, Zhouping Tang Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China Abstract: Stroke is a clinical disease with high incidence, high disability rate, and high mortality. But effective and safe therapy for stroke remains limited. Adult mesenchymal stromal cells (MSCs perform a variety of therapeutic functions. MSC delivery improves neurological outcomes in ischemic stroke models via neurorestorative and neuroprotective effects such as angiogenic effects, promoting endogenous proliferation, and reducing apoptosis and inflammation. MSC secretome also showed powerful therapeutic effects as a cell-based therapy in animal experiments. Several clinical trials on MSC implantation via different routes have now been completed in patients with stroke. Although challenges such as immunogenicity of allo-MSCs and large-scale production strategies need to be overcome, MSCs can be considered as a promising potential therapy for ischemic stroke. Keywords: mesenchymal stromal cell, stroke, therapy, transplantation, exosomes

  10. A Case of Placental Mesenchymal Dysplasia

    Directory of Open Access Journals (Sweden)

    Shigeki Taga

    2013-01-01

    Full Text Available Placental mesenchymal dysplasia (PMD rarely complicates with pregnancy. A 30-year-old woman, gravida 3, para 3, presenting with placentomegaly, was referred to our department at 18 weeks of gestation. An ultrasonography revealed a normal fetus with a large multicystic placenta, measuring 125 × 42 × 80 mm. The border between the lesion and normal region was not clear. Color doppler revealed little blood flow in the lesion. Magnetic resonance imaging revealed normal fetus and a large multicystic placenta. Serum human chorionic gonadotropin level was 20124.97 U/L, which was normal at 20 weeks of gestation. Thus, placental mesenchymal dysplasia rather than hydatidiform mole with coexistent fetus was suspected. Then, routine checkup was continued. Because she had the history of Cesarean section, an elective Cesarean section was performed at 37 weeks of gestation, and 2520 g female infant with apgar score 8/9 was delivered. The baby was normal with no evidence of Beckwith-Wiedemann syndrome. Placenta of 20 × 16 × 2 cm, weighing 720 g, was bulky with grape like vesicles involving whole placenta. Microscopic examination revealed dilated villi and vessels with thick wall which was lacking trophoblast proliferation. Large hydropic stem villi with myxomatous struma and cistern formation were seen. PMD was histopathologically confirmed.

  11. Mesenchymal Stem Cells in Neurodegenerative Diseases

    Directory of Open Access Journals (Sweden)

    Olcay Ergurhan Kiroglu

    2015-03-01

    Full Text Available Neurodegenerative diseases are almost incurable, debilitating, and they might be fatal, because of limited neurogenesis in nervous system, presence of inhibitory substances and inhibition of recovery due to development of glial scar. Despite many treatment strategies of neurodegenerative diseases no full cure has been achieved. The successful results for mesenchymal stem cells applications on muscles, heart and liver diseases and the application of these cells to the damaged area in particular, hypoxia, inflammation and apoptosis promise hope of using them for neurodegenerative diseases. Mesenchymal stem cells applications constitute a vascular and neuronal phenotype in Parkinsons disease, Huntingtons disease, Amyotrophic lateral sclerosis and Alzheimers disease. Stem cells release bioactive agents that lead to suppression of local immune system, reduction of free radicals, increase in angiogenesis, inhibition of fibrosis, and apoptosis. In addition, tissue stem cells, increase neuronal healing, stimulate proliferation and differentiation. These findings show that stem cells might be a hope of a cure in the treatment of neurodegenerative diseases and intensive work on this issue should continue.

  12. Viability of mesenchymal stem cells during electrospinning

    Directory of Open Access Journals (Sweden)

    G. Zanatta

    2012-02-01

    Full Text Available Tissue engineering is a technique by which a live tissue can be re-constructed and one of its main goals is to associate cells with biomaterials. Electrospinning is a technique that facilitates the production of nanofibers and is commonly used to develop fibrous scaffolds to be used in tissue engineering. In the present study, a different approach for cell incorporation into fibrous scaffolds was tested. Mesenchymal stem cells were extracted from the wall of the umbilical cord and mononuclear cells from umbilical cord blood. Cells were re-suspended in a 10% polyvinyl alcohol solution and subjected to electrospinning for 30 min under a voltage of 21 kV. Cell viability was assessed before and after the procedure by exclusion of dead cells using trypan blue staining. Fiber diameter was observed by scanning electron microscopy and the presence of cells within the scaffolds was analyzed by confocal laser scanning microscopy. After electrospinning, the viability of mesenchymal stem cells was reduced from 88 to 19.6% and the viability of mononuclear cells from 99 to 8.38%. The loss of viability was possibly due to the high viscosity of the polymer solution, which reduced the access to nutrients associated with electric and mechanical stress during electrospinning. These results suggest that the incorporation of cells during fiber formation by electrospinning is a viable process that needs more investigation in order to find ways to protect cells from damage.

  13. Cadherin-6B undergoes macropinocytosis and clathrin-mediated endocytosis during cranial neural crest cell EMT.

    Science.gov (United States)

    Padmanabhan, Rangarajan; Taneyhill, Lisa A

    2015-05-01

    The epithelial-to-mesenchymal transition (EMT) is important for the formation of migratory neural crest cells during development and is co-opted in human diseases such as cancer metastasis. Chick premigratory cranial neural crest cells lose intercellular contacts, mediated in part by Cadherin-6B (Cad6B), migrate extensively, and later form a variety of adult derivatives. Importantly, modulation of Cad6B is crucial for proper neural crest cell EMT. Although Cad6B possesses a long half-life, it is rapidly lost from premigratory neural crest cell membranes, suggesting the existence of post-translational mechanisms during EMT. We have identified a motif in the Cad6B cytoplasmic tail that enhances Cad6B internalization and reduces the stability of Cad6B upon its mutation. Furthermore, we demonstrate for the first time that Cad6B is removed from premigratory neural crest cells through cell surface internalization events that include clathrin-mediated endocytosis and macropinocytosis. Both of these processes are dependent upon the function of dynamin, and inhibition of Cad6B internalization abrogates neural crest cell EMT and migration. Collectively, our findings reveal the significance of post-translational events in controlling cadherins during neural crest cell EMT and migration. © 2015. Published by The Company of Biologists Ltd.

  14. Extraskeletal mesenchymal chondrosarcoma of the carotid space: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Huh, Sun; Hong, Hyun Sook; Kwak, Jeong Ja; Park, Ji Sang; Jeong, Sun Hye [Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon (Korea, Republic of)

    2015-05-15

    Chondrosarcoma is a commonly encountered malignant cartilaginous tumor. However, only 1% of chondrosarcomas arise in the extraskeletal region. The pathologic types of this tumor include mesenchymal, myxoid, and low grade. A mesenchymal chondrosarcoma is a rare, highly malignant cartilaginous tumor that is rarely encountered, and it shows similar imaging features to other malignant soft-tissue tumors. Here, we report a mesenchymal chondrosarcoma presenting as a palpable mass in the neck, arising in the carotid space, which is also known as the retrostyloid parapharyngeal space.

  15. A 3.7 kb fragment of the mouse Scn10a gene promoter directs neural crest but not placodal lineage EGFP expression in a transgenic animal.

    Science.gov (United States)

    Lu, Van B; Ikeda, Stephen R; Puhl, Henry L

    2015-05-20

    Under physiological conditions, the voltage-gated sodium channel Nav1.8 is expressed almost exclusively in primary sensory neurons. The mechanism restricting Nav1.8 expression is not entirely clear, but we have previously described a 3.7 kb fragment of the Scn10a promoter capable of recapitulating the tissue-specific expression of Nav1.8 in transfected neurons and cell lines (Puhl and Ikeda, 2008). To validate these studies in vivo, a transgenic mouse encoding EGFP under the control of this putative sensory neuron specific promoter was generated and characterized in this study. Approximately 45% of dorsal root ganglion neurons of transgenic mice were EGFP-positive (mean diameter = 26.5 μm). The majority of EGFP-positive neurons bound isolectin B4, although a small percentage (∼10%) colabeled with markers of A-fiber neurons. EGFP expression correlated well with the presence of Nav1.8 transcript (95%), Nav1.8-immunoreactivity (70%), and TTX-R INa (100%), although not all Nav1.8-expressing neurons expressed EGFP. Several cranial sensory ganglia originating from neurogenic placodes, such as the nodose ganglion, failed to express EGFP, suggesting that additional regulatory elements dictate Scn10a expression in placodal-derived sensory neurons. EGFP was also detected in discrete brain regions of transgenic mice. Quantitative PCR and Nav1.8-immunoreactivity confirmed Nav1.8 expression in the amygdala, brainstem, globus pallidus, lateral and paraventricular hypothalamus, and olfactory tubercle. TTX-R INa recorded from EGFP-positive hypothalamic neurons demonstrate the usefulness of this transgenic line to study novel roles of Nav1.8 beyond sensory neurons. Overall, Scn10a-EGFP transgenic mice recapitulate the majority of the Nav1.8 expression pattern in neural crest-derived sensory neurons. Copyright © 2015 the authors 0270-6474/15/358021-14$15.00/0.

  16. Dynamics of neural cryptography.

    Science.gov (United States)

    Ruttor, Andreas; Kinzel, Wolfgang; Kanter, Ido

    2007-05-01

    Synchronization of neural networks has been used for public channel protocols in cryptography. In the case of tree parity machines the dynamics of both bidirectional synchronization and unidirectional learning is driven by attractive and repulsive stochastic forces. Thus it can be described well by a random walk model for the overlap between participating neural networks. For that purpose transition probabilities and scaling laws for the step sizes are derived analytically. Both these calculations as well as numerical simulations show that bidirectional interaction leads to full synchronization on average. In contrast, successful learning is only possible by means of fluctuations. Consequently, synchronization is much faster than learning, which is essential for the security of the neural key-exchange protocol. However, this qualitative difference between bidirectional and unidirectional interaction vanishes if tree parity machines with more than three hidden units are used, so that those neural networks are not suitable for neural cryptography. In addition, the effective number of keys which can be generated by the neural key-exchange protocol is calculated using the entropy of the weight distribution. As this quantity increases exponentially with the system size, brute-force attacks on neural cryptography can easily be made unfeasible.

  17. Resolving time and space constraints during neural crest formation and delamination.

    Science.gov (United States)

    Duband, Jean-Loup; Dady, Alwyn; Fleury, Vincent

    2015-01-01

    A striking feature of neural crest development in vertebrates is that all the specification, delamination, migration, and differentiation steps occur consecutively in distinct areas of the embryo and at different timings of development. The significance and consequences of this partition into clearly separated events are not fully understood yet, but it ought to be related to the necessity of controlling precisely and independently each step, given the wide array of cell types and tissues derived from the neural crest and the long duration of their development spanning almost the entire embryonic life. In this chapter, using the examples of early neural crest induction and delamination, we discuss how time and space constraints influence their development and describe the molecular and cellular responses that are employed by cells to adapt. In the first example, we analyze how cell sorting and cell movements cooperate to allow nascent neural crest cells, which are initially mingled with other neurectodermal progenitors after induction, to segregate from the neural tube and ectoderm populations and settle at the apex of the neural tube prior to migration. In the second example, we examine how cadherins drive the entire process of neural crest segregation from the rest of the neurectoderm by their dual role in mediating first cell sorting and cohesion during specification and later in promoting their delamination. In the third example, we describe how the expression and activity of the transcription factors known to drive epithelium-to-mesenchyme transition (EMT) are regulated timely and spatially by the cellular machinery so that they can alternatively and successively regulate neural crest specification and delamination. In the last example, we briefly tackle the problem of how factors triggering EMT may elicit different cell responses in neural tube and neural crest progenitors. © 2015 Elsevier Inc. All rights reserved.

  18. ANT Advanced Neural Tool

    Energy Technology Data Exchange (ETDEWEB)

    Labrador, I.; Carrasco, R.; Martinez, L.

    1996-07-01

    This paper describes a practical introduction to the use of Artificial Neural Networks. Artificial Neural Nets are often used as an alternative to the traditional symbolic manipulation and first order logic used in Artificial Intelligence, due the high degree of difficulty to solve problems that can not be handled by programmers using algorithmic strategies. As a particular case of Neural Net a Multilayer Perception developed by programming in C language on OS9 real time operating system is presented. A detailed description about the program structure and practical use are included. Finally, several application examples that have been treated with the tool are presented, and some suggestions about hardware implementations. (Author) 15 refs.

  19. Bone marrow mesenchymal stem cells stimulate proliferation and neuronal differentiation of retinal progenitor cells.

    Directory of Open Access Journals (Sweden)

    Jing Xia

    Full Text Available During retina development, retinal progenitor cell (RPC proliferation and differentiation are regulated by complex inter- and intracellular interactions. Bone marrow mesenchymal stem cells (BMSCs are reported to express a variety of cytokines and neurotrophic factors, which have powerful trophic and protective functions for neural tissue-derived cells. Here, we show that the expanded RPC cultures treated with BMSC-derived conditioned medium (CM which was substantially enriched for bFGF and CNTF, expressed clearly increased levels of nuclear receptor TLX, an essential regulator of neural stem cell (NSC self-renewal, as well as betacellulin (BTC, an EGF-like protein described as supporting NSC expansion. The BMSC CM- or bFGF-treated RPCs also displayed an obviously enhanced proliferation capability, while BMSC CM-derived bFGF knocked down by anti-bFGF, the effect of BMSC CM on enhancing RPC proliferation was partly reversed. Under differentiation conditions, treatment with BMSC CM or CNTF markedly favoured RPC differentiation towards retinal neurons, including Brn3a-positive retinal ganglion cells (RGCs and rhodopsin-positive photoreceptors, and clearly diminished retinal glial cell differentiation. These findings demonstrate that BMSCs supported RPC proliferation and neuronal differentiation which may be partly mediated by BMSC CM-derived bFGF and CNTF, reveal potential limitations of RPC culture systems, and suggest a means for optimizing RPC cell fate determination in vitro.

  20. Hepatocyte growth factor mediates mesenchymal stem cell–induced recovery in multiple sclerosis models.

    Science.gov (United States)

    Bai, Lianhua; Lennon, Donald P; Caplan, Arnold I; DeChant, Anne; Hecker, Jordan; Kranso, Janet; Zaremba, Anita; Miller, Robert H

    2012-06-01

    Mesenchymal stem cells (MSCs) have emerged as a potential therapy for a range of neural insults. In animal models of multiple sclerosis, an autoimmune disease that targets oligodendrocytes and myelin, treatment with human MSCs results in functional improvement that reflects both modulation of the immune response and myelin repair. Here we demonstrate that conditioned medium from human MSCs (MSC-CM) reduces functional deficits in mouse MOG35–55-induced experimental autoimmune encephalomyelitis (EAE) and promotes the development of oligodendrocytes and neurons. Functional assays identified hepatocyte growth factor (HGF) and its primary receptor cMet as critical in MSC-stimulated recovery in EAE, neural cell development and remyelination. Active MSC-CM contained HGF, and exogenously supplied HGF promoted recovery in EAE, whereas cMet and antibodies to HGF blocked the functional recovery mediated by HGF and MSC-CM. Systemic treatment with HGF markedly accelerated remyelination in lysolecithin-induced rat dorsal spinal cord lesions and in slice cultures. Together these data strongly implicate HGF in mediating MSC-stimulated functional recovery in animal models of multiple sclerosis.

  1. Cryopreservation and revival of mesenchymal stromal cells

    DEFF Research Database (Denmark)

    Haack-Sørensen, Mandana; Kastrup, Jens

    2011-01-01

    Over the past few years, the pace of preclinical stem cell research is astonishing and adult stem cells have become the subject of intense research. Due to the presence of promising supporting preclinical data, human clinical trials for stem cell regenerative treatment of various diseases have been...... initiated. As there has been a precedent for the use of bone marrow stem cells in the treatment of hematological malignancies and ischemic heart diseases through randomized clinical safety and efficacy trials, the development of new therapies based on culture-expanded human mesenchymal stromal cells (MSCs......) opens up new possibilities for cell therapy. To facilitate these applications, cryopreservation and long-term storage of MSCs becomes an absolute necessity. As a result, optimization of this cryopreservation protocol is absolutely critical. The major challenge during cellular cryopreservation...

  2. Treatment of osteoarthritis with mesenchymal stem cells.

    Science.gov (United States)

    Wang, Wen; Cao, Wei

    2014-06-01

    Osteoarthritis (OA) is one of the most prevalent joint diseases with prominent symptoms affecting the daily life of millions of middle aged and elderly people. Despite this, there are no successful medical interventions that can prevent the progressive destruction of OA joints. The onset of pathological changes in OA is associated with deviant activity of mesenchymal stem cells (MSCs), the multipotent precursors of connective tissue cells that reside in joints. Current therapies for OA have resulted in poor clinical outcomes without repairing the damaged cartilage. Intra-articular delivery of culture-expanded MSCs has opened new avenues of OA treatment. Pre-clinical and clinical trials demonstrated the feasibility, safety, and efficacy of MSC therapy. The Wnt/β-catenin, bone morphogenetic protein 2, Indian hedgehog, and Mitogen-activated protein kinase signaling pathways have been demonstrated to be involved in OA and the mechanism of action of MSC therapies.

  3. Reprogramming of mesenchymal stem cells by oncogenes.

    Science.gov (United States)

    Eid, Josiane E; Garcia, Christina B

    2015-06-01

    Mesenchymal stem cells (MSCs) originate from embryonic mesoderm and give rise to the multiple lineages of connective tissues. Transformed MSCs develop into aggressive sarcomas, some of which are initiated by specific chromosomal translocations that generate fusion proteins with potent oncogenic properties. The sarcoma oncogenes typically prime MSCs through aberrant reprogramming. They dictate commitment to a specific lineage but prevent mature differentiation, thus locking the cells in a state of proliferative precursors. Deregulated expression of lineage-specific transcription factors and controllers of chromatin structure play a central role in MSC reprogramming and sarcoma pathogenesis. This suggests that reversing the epigenetic aberrancies created by the sarcoma oncogenes with differentiation-related reagents holds great promise as a beneficial addition to sarcoma therapies. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Mesenchymal Stem Cells: Angels or Demons?

    Directory of Open Access Journals (Sweden)

    Rebecca S. Y. Wong

    2011-01-01

    Full Text Available Mesenchymal stem cells (MSCs have been used in cell-based therapy in various disease conditions such as graft-versus-host and heart diseases, osteogenesis imperfecta, and spinal cord injuries, and the results have been encouraging. However, as MSC therapy gains popularity among practitioners and researchers, there have been reports on the adverse effects of MSCs especially in the context of tumour modulation and malignant transformation. These cells have been found to enhance tumour growth and metastasis in some studies and have been related to anticancer-drug resistance in other instances. In addition, various studies have also reported spontaneous malignant transformation of MSCs. The mechanism of the modulatory behaviour and the tumorigenic potential of MSCs, warrant urgent exploration, and the use of MSCs in patients with cancer awaits further evaluation. However, if MSCs truly play a role in tumour modulation, they can also be potential targets of cancer treatment.

  5. Mesenchymal stem cell assays and applications

    Directory of Open Access Journals (Sweden)

    CarloAlberto Redi

    2011-11-01

    Full Text Available Among the many types of adult, or better, somatic, stem cells, mesenchymal stem cells (marrow-derived stromal cells, MSC are those more versatile in changing their phenotype during differentiation: from smooth muscle, adipocyte, bone and cartilage cells to name a few. In addition, they are present in large number in adults and relatively easy to isolate and colture. All these features simply explain the already large number of application that their use allow in rigenerative medicine, not to tell about researches in which they play a crucial role in understanding the meaning of stemness and stem cell niche and the other several conceptual paradigms framing the fascinating field of stem cell biology. Having clear in mind this situation.....

  6. Spheroid Culture of Mesenchymal Stem Cells

    Directory of Open Access Journals (Sweden)

    Zoe Cesarz

    2016-01-01

    Full Text Available Compared with traditional 2D adherent cell culture, 3D spheroidal cell aggregates, or spheroids, are regarded as more physiological, and this technique has been exploited in the field of oncology, stem cell biology, and tissue engineering. Mesenchymal stem cells (MSCs cultured in spheroids have enhanced anti-inflammatory, angiogenic, and tissue reparative/regenerative effects with improved cell survival after transplantation. Cytoskeletal reorganization and drastic changes in cell morphology in MSC spheroids indicate a major difference in mechanophysical properties compared with 2D culture. Enhanced multidifferentiation potential, upregulated expression of pluripotency marker genes, and delayed replicative senescence indicate enhanced stemness in MSC spheroids. Furthermore, spheroid formation causes drastic changes in the gene expression profile of MSC in microarray analyses. In spite of these significant changes, underlying molecular mechanisms and signaling pathways triggering and sustaining these changes are largely unknown.

  7. Placental mesenchymal dysplasia: What every radiologist needs to know

    Directory of Open Access Journals (Sweden)

    Disha Mittal

    2017-01-01

    Full Text Available Placental mesenchymal dysplasia (PMD is an uncommon vascular anomaly of the placenta characterized by placentomegaly with multicystic placental lesion on ultrasonography and mesenchymal stem villous hyperplasia on histopathology. Placental mesenchymal dysplasia should be considered in the differential diagnosis of cases of multicystic placental lesion such as molar pregnancy, chorioangioma, subchorionic hematoma, and spontaneous abortion with hydropic placental changes. However, lack of high-velocity signals inside the lesion and a normal karyotype favor a diagnosis of PMD. PMD must be differentiated from gestational trophoblastic disease because management and outcomes differ. We report the case of an 18-year-old female at 15 weeks of gestation with sonographic findings suggestive of placental mesenchymal dysplasia. The diagnosis was confirmed on histopathology.

  8. Labeling and Imaging Mesenchymal Stem Cells with Quantum Dots

    Science.gov (United States)

    Mesenchymal stem cells (MSCs) are multipotent cells with the potential to differentiate into bone, cartilage, adipose and muscle cells. Adult derived MSCs are being actively investigated because of their potential to be utilized for therapeutic cell-based transplantation. Methods...

  9. Mesenchymal stem cell therapy for nonmusculoskeletal diseases: emerging applications.

    Science.gov (United States)

    Kuo, Tom K; Ho, Jennifer H; Lee, Oscar K

    2009-01-01

    Mesenchymal stem cells are stem/progenitor cells originated from the mesoderm and can different into multiple cell types of the musculoskeletal system. The vast differentiation potential and the relative ease for culture expansion have established mesenchymal stem cells as the building blocks in cell therapy and tissue engineering applications for a variety of musculoskeletal diseases, including repair of fractures and bone defects, cartilage regeneration, treatment of osteonecrosis of the femoral head, and correction of genetic diseases such as osteogenesis imperfect. However, research in the past decade has revealed differentiation potentials of mesenchymal stem cells beyond lineages of the mesoderm, suggesting broader applications than originally perceived. In this article, we review the recent developments in mesenchymal stem cell research with respect to their emerging properties and applications in nonmusculoskeletal diseases.

  10. The transcriptional coactivator TAZ regulates mesenchymal differentiation in malignant glioma

    NARCIS (Netherlands)

    Bhat, Krishna P. L.; Salazar, Katrina L.; Balasubramaniyan, Veerakumar; Wani, Khalida; Heathcock, Lindsey; Hollingsworth, Faith; James, Johanna D.; Gumin, Joy; Diefes, Kristin L.; Kim, Se Hoon; Turski, Alice; Azodi, Yasaman; Yang, Yuhui; Doucette, Tiffany; Colman, Howard; Sulman, Erik P.; Lang, Frederick F.; Rao, Ganesh; Copray, Sjef; Vaillant, Brian D.; Aldape, Kenneth D.

    2011-01-01

    Recent molecular classification of glioblastoma (GBM) has shown that patients with a mesenchymal (MES) gene expression signature exhibit poor overall survival and treatment resistance. Using regulatory network analysis of available expression microarray data sets of GBM, including The Cancer Genome

  11. Protons sensitize epithelial cells to mesenchymal transition.

    Science.gov (United States)

    Wang, Minli; Hada, Megumi; Saha, Janapriya; Sridharan, Deepa M; Pluth, Janice M; Cucinotta, Francis A

    2012-01-01

    Proton radiotherapy has gained more favor among oncologists as a treatment option for localized and deep-seated tumors. In addition, protons are a major constituent of the space radiation astronauts receive during space flights. The potential for these exposures to lead to, or enhance cancer risk has not been well studied. Our objective is to study the biological effects of low energy protons on epithelial cells and its propensity to enhance transforming growth factor beta 1 (TGFβ1)-mediated epithelial-mesenchymal transition (EMT), a process occurring during tumor progression and critical for invasion and metastasis. Non-transformed mink lung epithelial cells (Mv1Lu) and hTERT- immortalized human esophageal epithelial cells (EPC) were used in this study. EMT was identified by alterations in cell morphology, EMT-related gene expression changes determined using real-time PCR, and EMT changes in specific cellular markers detected by immunostaining and western blotting. Although TGFβ1 treatment alone is able to induce EMT in both Mv1Lu and EPC cells, low energy protons (5 MeV) at doses as low as 0.1 Gy can enhance TGFβ1 induced EMT. Protons alone can also induce a mild induction of EMT. SD208, a potent TGFβ Receptor 1 (TGFβR1) kinase inhibitor, can efficiently block TGFβ1/Smad signaling and attenuate EMT induction. We suggest a model for EMT after proton irradiation in normal and cancerous tissue based on our results that showed that low and high doses of protons can sensitize normal human epithelial cells to mesenchymal transition, more prominently in the presence of TGFβ1, but also in the absence of TGFβ1.

  12. Hidden neural networks

    DEFF Research Database (Denmark)

    Krogh, Anders Stærmose; Riis, Søren Kamaric

    1999-01-01

    A general framework for hybrids of hidden Markov models (HMMs) and neural networks (NNs) called hidden neural networks (HNNs) is described. The article begins by reviewing standard HMMs and estimation by conditional maximum likelihood, which is used by the HNN. In the HNN, the usual HMM probability...... parameters are replaced by the outputs of state-specific neural networks. As opposed to many other hybrids, the HNN is normalized globally and therefore has a valid probabilistic interpretation. All parameters in the HNN are estimated simultaneously according to the discriminative conditional maximum...... likelihood criterion. The HNN can be viewed as an undirected probabilistic independence network (a graphical model), where the neural networks provide a compact representation of the clique functions. An evaluation of the HNN on the task of recognizing broad phoneme classes in the TIMIT database shows clear...

  13. [Neural codes for perception].

    Science.gov (United States)

    Romo, R; Salinas, E; Hernández, A; Zainos, A; Lemus, L; de Lafuente, V; Luna, R

    This article describes experiments designed to show the neural codes associated with the perception and processing of tactile information. The results of these experiments have shown the neural activity correlated with tactile perception. The neurones of the primary somatosensory cortex (S1) represent the physical attributes of tactile perception. We found that these representations correlated with tactile perception. By means of intracortical microstimulation we demonstrated the causal relationship between S1 activity and tactile perception. In the motor areas of the frontal lobe is to be found the connection between sensorial and motor representation whilst decisions are being taken. S1 generates neural representations of the somatosensory stimuli which seen to be sufficient for tactile perception. These neural representations are subsequently processed by central areas to S1 and seem useful in perception, memory and decision making.

  14. Neural Oscillators Programming Simplified

    Directory of Open Access Journals (Sweden)

    Patrick McDowell

    2012-01-01

    Full Text Available The neurological mechanism used for generating rhythmic patterns for functions such as swallowing, walking, and chewing has been modeled computationally by the neural oscillator. It has been widely studied by biologists to model various aspects of organisms and by computer scientists and robotics engineers as a method for controlling and coordinating the gaits of walking robots. Although there has been significant study in this area, it is difficult to find basic guidelines for programming neural oscillators. In this paper, the authors approach neural oscillators from a programmer’s point of view, providing background and examples for developing neural oscillators to generate rhythmic patterns that can be used in biological modeling and robotics applications.

  15. Neural cryptography with feedback.

    Science.gov (United States)

    Ruttor, Andreas; Kinzel, Wolfgang; Shacham, Lanir; Kanter, Ido

    2004-04-01

    Neural cryptography is based on a competition between attractive and repulsive stochastic forces. A feedback mechanism is added to neural cryptography which increases the repulsive forces. Using numerical simulations and an analytic approach, the probability of a successful attack is calculated for different model parameters. Scaling laws are derived which show that feedback improves the security of the system. In addition, a network with feedback generates a pseudorandom bit sequence which can be used to encrypt and decrypt a secret message.

  16. Neural cryptography with feedback

    Science.gov (United States)

    Ruttor, Andreas; Kinzel, Wolfgang; Shacham, Lanir; Kanter, Ido

    2004-04-01

    Neural cryptography is based on a competition between attractive and repulsive stochastic forces. A feedback mechanism is added to neural cryptography which increases the repulsive forces. Using numerical simulations and an analytic approach, the probability of a successful attack is calculated for different model parameters. Scaling laws are derived which show that feedback improves the security of the system. In addition, a network with feedback generates a pseudorandom bit sequence which can be used to encrypt and decrypt a secret message.

  17. Neural network applications

    Science.gov (United States)

    Padgett, Mary L.; Desai, Utpal; Roppel, T.A.; White, Charles R.

    1993-01-01

    A design procedure is suggested for neural networks which accommodates the inclusion of such knowledge-based systems techniques as fuzzy logic and pairwise comparisons. The use of these procedures in the design of applications combines qualitative and quantitative factors with empirical data to yield a model with justifiable design and parameter selection procedures. The procedure is especially relevant to areas of back-propagation neural network design which are highly responsive to the use of precisely recorded expert knowledge.

  18. Building Neural Net Software

    OpenAIRE

    Neto, João Pedro; Costa, José Félix

    1999-01-01

    In a recent paper [Neto et al. 97] we showed that programming languages can be translated on recurrent (analog, rational weighted) neural nets. The goal was not efficiency but simplicity. Indeed we used a number-theoretic approach to machine programming, where (integer) numbers were coded in a unary fashion, introducing a exponential slow down in the computations, with respect to a two-symbol tape Turing machine. Implementation of programming languages in neural nets turns to be not only theo...

  19. NEMEFO: NEural MEteorological FOrecast

    Energy Technology Data Exchange (ETDEWEB)

    Pasero, E.; Moniaci, W.; Meindl, T.; Montuori, A. [Polytechnic of Turin (Italy). Dept. of Electronics

    2004-07-01

    Artificial Neural Systems are a well-known technique used to classify and recognize objects. Introducing the time dimension they can be used to forecast numerical series. NEMEFO is a ''nowcasting'' tool, which uses both statistical and neural systems to forecast meteorological data in a restricted area close to a meteorological weather station in a short time range (3 hours). Ice, fog, rain are typical events which can be anticipated by NEMEFO. (orig.)

  20. Nestin-GFP Transgene Reveals Neural Precursor Cells in Adult Skeletal Muscle

    Science.gov (United States)

    Birbrair, Alexander; Wang, Zhong-Min; Messi, Maria Laura; Enikolopov, Grigori N.; Delbono, Osvaldo

    2011-01-01

    Background Therapy for neural lesions or degenerative diseases relies mainly on finding transplantable active precursor cells. Identifying them in peripheral tissues accessible for biopsy, outside the central nervous system, would circumvent the serious immunological and ethical concerns impeding cell therapy. Methodology/Principal Findings In this study, we isolated neural progenitor cells in cultured adult skeletal muscle from transgenic mice in which nestin regulatory elements control GFP expression. These cells also expressed the early neural marker Tuj1 and light and heavy neurofilament but not S100β, indicating that they express typical neural but not Schwann cell markers. GFP+/Tuj1+ cells were also negative for the endothelial and pericyte markers CD31 and α-smooth muscle actin, respectively. We established their a) functional response to glutamate in patch-clamp recordings; b) interstitial mesenchymal origin; c) replicative capacity; and d) the environment necessary for their survival after fluorescence-activated cell sorting. Conclusions/Significance We propose that the decline in nestin-GFP expression in muscle progenitor cells and its persistence in neural precursor cells in muscle cultures provide an invaluable tool for isolating a population of predifferentiated neural cells with therapeutic potential. PMID:21304812

  1. Spatial and temporal variations in extracellular matrix of periocular and corneal regions during corneal stromal development.

    Science.gov (United States)

    Doane, K J; Ting, W H; McLaughlin, J S; Birk, D E

    1996-03-01

    The development of the avian corneal stroma occurs in discrete developmental stages. During this sequence of events, the neural crest-derived corneal fibroblast precursor cells are surrounded by distinct extracellular matrices which change both spatially and temporally. To elucidate the role of these matrices, extracellular matrix components in the periocular mesenchyme and cornea were analysed prior to and during migration and differentiation of corneal fibroblasts using antibodies against collagens, proteoglycans and glycoproteins. Previous work has concentrated on the matrix of the corneal stroma rather than the matrix of the periocular mesenchyme. Since the precursors of the corneal fibroblasts are present within the must migrate through the periocular mesenchyme prior to entry into the cornea proper, this environment was fully evaluated. The present study documents the matrix composition of both the cornea and periocular mesenchyme at developmental stages that are prior to and after initiation of corneal invasion by the corneal fibroblast precursors. Variations in matrix molecules comprising both the periocular mesenchyme and cornea were demonstrated. These include changes in the distribution of collagen types I, II, III, IV and VI; the proteoglycans decorin and lumican; as well as the adhesive glycoproteins tenascin, fibronectin and laminin. It is hypothesized that the variations in matrix localization are important in the regulation of cell migration and differentiation during normal corneal development. Any regulation is likely to involve a combination of components found in the extracellular matrices and therefore, a consideration of the matrix rather than isolated components is required.

  2. Perivascular Mesenchymal Stem Cells From the Adult Human Brain Harbor No Instrinsic Neuroectodermal but High Mesodermal Differentiation Potential.

    Science.gov (United States)

    Lojewski, Xenia; Srimasorn, Sumitra; Rauh, Juliane; Francke, Silvan; Wobus, Manja; Taylor, Verdon; Araúzo-Bravo, Marcos J; Hallmeyer-Elgner, Susanne; Kirsch, Matthias; Schwarz, Sigrid; Schwarz, Johannes; Storch, Alexander; Hermann, Andreas

    2015-10-01

    Brain perivascular cells have recently been identified as a novel mesodermal cell type in the human brain. These cells reside in the perivascular niche and were shown to have mesodermal and, to a lesser extent, tissue-specific differentiation potential. Mesenchymal stem cells (MSCs) are widely proposed for use in cell therapy in many neurological disorders; therefore, it is of importance to better understand the "intrinsic" MSC population of the human brain. We systematically characterized adult human brain-derived pericytes during in vitro expansion and differentiation and compared these cells with fetal and adult human brain-derived neural stem cells (NSCs) and adult human bone marrow-derived MSCs. We found that adult human brain pericytes, which can be isolated from the hippocampus and from subcortical white matter, are-in contrast to adult human NSCs-easily expandable in monolayer cultures and show many similarities to human bone marrow-derived MSCs both regarding both surface marker expression and after whole transcriptome profile. Human brain pericytes showed a negligible propensity for neuroectodermal differentiation under various differentiation conditions but efficiently generated mesodermal progeny. Consequently, human brain pericytes resemble bone marrow-derived MSCs and might be very interesting for possible autologous and endogenous stem cell-based treatment strategies and cell therapeutic approaches for treating neurological diseases. Perivascular mesenchymal stem cells (MSCs) recently gained significant interest because of their appearance in many tissues including the human brain. MSCs were often reported as being beneficial after transplantation in the central nervous system in different neurological diseases; therefore, adult brain perivascular cells derived from human neural tissue were systematically characterized concerning neural stem cell and MSC marker expression, transcriptomics, and mesodermal and inherent neuroectodermal differentiation

  3. Co-culture with Sertoli cells promotes proliferation and migration of umbilical cord mesenchymal stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Fenxi, E-mail: fxzhang0824@gmail.com [Department of Anatomy, Sanquan College, Xinxiang Medical University, Henan 453003, People' s Republic of China (China); Hong, Yan; Liang, Wenmei [Department of Histology and Embryology, Guiyang Medical University, Guizhou 550004, People' s Republic of China (China); Ren, Tongming [Department of Anatomy, Sanquan College, Xinxiang Medical University, Henan 453003, People' s Republic of China (China); Jing, Suhua [ICU Center, The Third Hospital of Xinxiang Medical University, Henan 453003, People' s Republic of China (China); Lin, Juntang [Stem Cell Center, Xinxiang Medical University, Henan 453003, People' s Republic of China (China)

    2012-10-12

    Highlights: Black-Right-Pointing-Pointer Co-culture of Sertoli cells (SCs) with human umbilical cord mesenchymal stem cells (UCMSCs). Black-Right-Pointing-Pointer Presence of SCs dramatically increased proliferation and migration of UCMSCs. Black-Right-Pointing-Pointer Presence of SCs stimulated expression of Mdm2, Akt, CDC2, Cyclin D, CXCR4, MAPKs. -- Abstract: Human umbilical cord mesenchymal stem cells (hUCMSCs) have been recently used in transplant therapy. The proliferation and migration of MSCs are the determinants of the efficiency of MSC transplant therapy. Sertoli cells are a kind of 'nurse' cells that support the development of sperm cells. Recent studies show that Sertoli cells promote proliferation of endothelial cells and neural stem cells in co-culture. We hypothesized that co-culture of UCMSCs with Sertoli cells may also promote proliferation and migration of UCMSCs. To examine this hypothesis, we isolated UCMSCs from human cords and Sertoli cells from mouse testes, and co-cultured them using a Transwell system. We found that UCMSCs exhibited strong proliferation ability and potential to differentiate to other cell lineages such as osteocytes and adipocytes. The presence of Sertoli cells in co-culture significantly enhanced the proliferation and migration potential of UCMSCs (P < 0.01). Moreover, these phenotypic changes were accompanied with upregulation of multiple genes involved in cell proliferation and migration including phospho-Akt, Mdm2, phospho-CDC2, Cyclin D1, Cyclin D3 as well as CXCR4, phospho-p44 MAPK and phospho-p38 MAPK. These findings indicate that Sertoli cells boost UCMSC proliferation and migration potential.

  4. Mesenchymal cells condensation-inducible mesh scaffolds for cartilage tissue engineering.

    Science.gov (United States)

    Kim, In Gul; Ko, Jaehoon; Lee, Hye Rim; Do, Sun Hee; Park, Kwideok

    2016-04-01

    Mesenchymal cells condensation is crucial in chondrogenic development. However current tissue-engineered scaffolds for chondrogenesis pay little attention to this phenomenon. In this study, we fabricate poly(l-lactide-co-glycolide) (PLGA)/poly(l-lactide) (PLLA) microfiber scaffolds and coat them with human fibroblast-derived matrix (hFDM) that is a decellularized extracellular matrix (ECM) obtained from in vitro cultured human lung fibroblasts (WI-38). Those scaffolds were then conjugated with heparin via EDC chemistry and subsequently immobilized with transforming growth factor (TGF)-β1. The amount of TGF-β1 was quantitatively measured and the release profile showed a continuous release of TGF-β1 for 4 weeks. Human umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) were seeded in four different scaffolds; control, fibronectin (FN)-coated, hFDM-coated, hFDM/TGF-β1 and subjected to chondrogenic differentiation in vitro for up to 28 days. Both hFDM and hFDM/TGF-β1 groups exhibited significantly more synthesis of glycosaminoglycan (GAG) and much better upregulation of chondrogenic markers expression. Interestingly, MSCs condensation that led to cell aggregates was clearly observed with time in the two hFDM-coated groups and the quantitative difference was obvious compared to the control and FN group. A mechanistic study in gene and protein level indicated that focal adhesion kinase (FAK) was involved at the early stage of cell adhesion and cell-cell contact-related markers, N-cadherin and neural cell adhesion molecule (NCAM), were highly up-regulated at later time point. In addition histological analysis proved that hFDM/TGF-β1 group was the most effective in forming neocartilage tissue in a rabbit articular cartilage defect model. Taken together, this study demonstrates not only the positive effect of hFDM on chondrogenesis of MSCs and cartilage repair but also provides an important insight toward the significance of in vitro mesenchymal

  5. Heterogeneity of expression of epithelial-mesenchymal transition (EMT markers in melanocytes and melanoma cell lines

    Directory of Open Access Journals (Sweden)

    Ji Eun eKim

    2013-05-01

    Full Text Available The epithelial-mesenchymal transition (EMT describes a reversible switch from an epithelial-like to a mesenchymal-like phenotype. It is essential for the development of the normal epithelium and also contributes to the invasive properties of carcinomas. At the molecular level, the EMT transition is characterised by a series of coordinated changes including downregulation of the junctional protein E-cadherin (CDH1, up-regulation of transcriptional repressors of E-cadherin such as Snail (SNAI1 and Slug (SNAI2, and up-regulation of N-cadherin. We wished to determine whether cultured normal melanocytes and melanoma cell lines, which are derived from the neural crest, showed signs of a similarly coordinated phenotypic switch. We investigated normal melanocytes and 25 cell lines derived from New Zealand patients with metastatic melanoma. Most lines had been previously genotyped for common mutations such as BRAF, NRAS, PIK3CA, TP53 and CDKN2A. Expression of E-cadherin, N-cadherin, MITF, Snail, Slug, Axl, p53 and Hdm2 was compared by western blotting. Normal melanocytes expressed each of these proteins except for Snail, while normal melanocytes and almost every melanoma line expressed Slug. Expression of individual markers among different melanoma lines varied from high to low or undetectable. Quantitation of western blots showed that expression of MITF-M, the melanocyte-specific isoform of MITF, was positively related to that of E-cadherin but inversely related to that of N-cadherin and Axl. There was also no apparent relationship between expression of any particular marker and the presence of BRAF, NRAS, PIK3CA, TP53 or CDKN2A mutations. The results suggest that melanomas do not show the classical epithelial and mesenchymal phenotypes but rather display either high E-cadherin/high MITF-M expression on one hand, or high N-cadherin/high Axl expression on the other. These may correspond to differentiated and invasive phenotypes in vivo.

  6. Conducting Polymers for Neural Prosthetic and Neural Interface Applications

    Science.gov (United States)

    2015-01-01

    Neural interfacing devices are an artificial mechanism for restoring or supplementing the function of the nervous system lost as a result of injury or disease. Conducting polymers (CPs) are gaining significant attention due to their capacity to meet the performance criteria of a number of neuronal therapies including recording and stimulating neural activity, the regeneration of neural tissue and the delivery of bioactive molecules for mediating device-tissue interactions. CPs form a flexible platform technology that enables the development of tailored materials for a range of neuronal diagnostic and treatment therapies. In this review the application of CPs for neural prostheses and other neural interfacing devices are discussed, with a specific focus on neural recording, neural stimulation, neural regeneration, and therapeutic drug delivery. PMID:26414302

  7. Mesenchymal cells reactivate Snail1 expression to drive three-dimensional invasion programs

    DEFF Research Database (Denmark)

    Rowe, R.G.; Li, X.Y.; Hu, Y.

    2009-01-01

    Epithelial-mesenchymal transition (EMT) is required for mesodermal differentiation during development. The zinc-finger transcription factor, Snail1, can trigger EMT and is sufficient to transcriptionally reprogram epithelial cells toward a mesenchymal phenotype during neoplasia and fibrosis. Whet...

  8. Hyperbolic Hopfield neural networks.

    Science.gov (United States)

    Kobayashi, M

    2013-02-01

    In recent years, several neural networks using Clifford algebra have been studied. Clifford algebra is also called geometric algebra. Complex-valued Hopfield neural networks (CHNNs) are the most popular neural networks using Clifford algebra. The aim of this brief is to construct hyperbolic HNNs (HHNNs) as an analog of CHNNs. Hyperbolic algebra is a Clifford algebra based on Lorentzian geometry. In this brief, a hyperbolic neuron is defined in a manner analogous to a phasor neuron, which is a typical complex-valued neuron model. HHNNs share common concepts with CHNNs, such as the angle and energy. However, HHNNs and CHNNs are different in several aspects. The states of hyperbolic neurons do not form a circle, and, therefore, the start and end states are not identical. In the quantized version, unlike complex-valued neurons, hyperbolic neurons have an infinite number of states.

  9. Neural Semantic Encoders.

    Science.gov (United States)

    Munkhdalai, Tsendsuren; Yu, Hong

    2017-04-01

    We present a memory augmented neural network for natural language understanding: Neural Semantic Encoders. NSE is equipped with a novel memory update rule and has a variable sized encoding memory that evolves over time and maintains the understanding of input sequences through read, compose and write operations. NSE can also access multiple and shared memories. In this paper, we demonstrated the effectiveness and the flexibility of NSE on five different natural language tasks: natural language inference, question answering, sentence classification, document sentiment analysis and machine translation where NSE achieved state-of-the-art performance when evaluated on publically available benchmarks. For example, our shared-memory model showed an encouraging result on neural machine translation, improving an attention-based baseline by approximately 1.0 BLEU.

  10. Gut Mesenchymal Stromal Cells in Immunity

    Directory of Open Access Journals (Sweden)

    Valeria Messina

    2017-01-01

    Full Text Available Mesenchymal stromal cells (MSCs, first found in bone marrow (BM, are the structural architects of all organs, participating in most biological functions. MSCs possess tissue-specific signatures that allow their discrimination according to their origin and location. Among their multiple functions, MSCs closely interact with immune cells, orchestrating their activity to maintain overall homeostasis. The phenotype of tissue MSCs residing in the bowel overlaps with myofibroblasts, lining the bottom walls of intestinal crypts (pericryptal or interspersed within intestinal submucosa (intercryptal. In Crohn’s disease, intestinal MSCs are tightly stacked in a chronic inflammatory milieu, which causes their enforced expression of Class II major histocompatibility complex (MHC. The absence of Class II MHC is a hallmark for immune-modulator and tolerogenic properties of normal MSCs and, vice versa, the expression of HLA-DR is peculiar to antigen presenting cells, that is, immune-activator cells. Interferon gamma (IFNγ is responsible for induction of Class II MHC expression on intestinal MSCs. The reversal of myofibroblasts/MSCs from an immune-modulator to an activator phenotype in Crohn’s disease results in the formation of a fibrotic tube subverting the intestinal structure. Epithelial metaplastic areas in this context can progress to dysplasia and cancer.

  11. Transcriptional networks in epithelial-mesenchymal transition.

    Directory of Open Access Journals (Sweden)

    Christo Venkov

    Full Text Available Epithelial-mesenchymal transition (EMT changes polarized epithelial cells into migratory phenotypes associated with loss of cell-cell adhesion molecules and cytoskeletal rearrangements. This form of plasticity is seen in mesodermal development, fibroblast formation, and cancer metastasis.Here we identify prominent transcriptional networks active during three time points of this transitional process, as epithelial cells become fibroblasts. DNA microarray in cultured epithelia undergoing EMT, validated in vivo, were used to detect various patterns of gene expression. In particular, the promoter sequences of differentially expressed genes and their transcription factors were analyzed to identify potential binding sites and partners. The four most frequent cis-regulatory elements (CREs in up-regulated genes were SRY, FTS-1, Evi-1, and GC-Box, and RNA inhibition of the four transcription factors, Atf2, Klf10, Sox11, and SP1, most frequently binding these CREs, establish their importance in the initiation and propagation of EMT. Oligonucleotides that block the most frequent CREs restrain EMT at early and intermediate stages through apoptosis of the cells.Our results identify new transcriptional interactions with high frequency CREs that modulate the stability of cellular plasticity, and may serve as targets for modulating these transitional states in fibroblasts.

  12. Mesenchymal stem cell therapy for liver fibrosis.

    Science.gov (United States)

    Eom, Young Woo; Shim, Kwang Yong; Baik, Soon Koo

    2015-09-01

    Currently, the most effective treatment for end-stage liver fibrosis is liver transplantation; however, transplantation is limited by a shortage of donor organs, surgical complications, immunological rejection, and high medical costs. Recently, mesenchymal stem cell (MSC) therapy has been suggested as an effective alternate approach for the treatment of hepatic diseases. MSCs have the potential to differentiate into hepatocytes, and therapeutic value exists in their immune-modulatory properties and secretion of trophic factors, such as growth factors and cytokines. In addition, MSCs can suppress inflammatory responses, reduce hepatocyte apoptosis, increase hepatocyte regeneration, regress liver fibrosis and enhance liver functionality. Despite these advantages, issues remain; MSCs also have fibrogenic potential and the capacity to promote tumor cell growth and oncogenicity. This paper summarizes the properties of MSCs for regenerative medicine and their therapeutic mechanisms and clinical application in the treatment of liver fibrosis. We also present several outstanding risks, including their fibrogenic potential and their capacity to promote pre-existing tumor cell growth and oncogenicity.

  13. Application of mesenchymal stem cells in paediatrics

    Directory of Open Access Journals (Sweden)

    Wawryk-Gawda Ewelina

    2017-09-01

    Full Text Available Mesenchymal stem cells (MSC were described by Friedenstein in the 1970s as being a group of bone marrow non-hematopoietic cells that are the source of fibroblasts. Since then, knowledge about the therapeutic potential of MSCs has significantly increased. MSCs are currently used for the treatment of many diseases, both in adults and children. MSCs are used successfully in the case of autoimmune diseases, including rheumatic diseases, diabetes mellitus type 1, gastroenterological and neurological diseases. Moreover, treatment of such organ disorders as damage or hypoxia through application of MSC therapy has shown to be satisfactory. In addition, there are some types of congenital disorders, including osteogenesis imperfecta and Spinal Muscular Atrophy, that may be treated with cellular therapy. Most studies showed no other adverse effects than fever. Our study is an analysis that particularly focuses on the registered trials and results of MSCs application to under 18 patients with acute, chronic, recurrent, resistance and corticosteroids types of Graft-versus-Host Disease (GvHD. Stem cells currently play an important role in the treatment of many diseases. Long-term studies conducted on animals have shown that cell therapy is both effective and safe. The number of indications for use of these cells in the course of treatment of people is constantly increasing. The results of subsequent studies provide important data justifying the application of MSCs in the course of treatment of many diseases whose treatment is ineffective when utilizing other approaches.

  14. Epigenetic Classification of Human Mesenchymal Stromal Cells

    Directory of Open Access Journals (Sweden)

    Danilo Candido de Almeida

    2016-02-01

    Full Text Available Standardization of mesenchymal stromal cells (MSCs is hampered by the lack of a precise definition for these cell preparations; for example, there are no molecular markers to discern MSCs and fibroblasts. In this study, we followed the hypothesis that specific DNA methylation (DNAm patterns can assist classification of MSCs. We utilized 190 DNAm profiles to address the impact of tissue of origin, donor age, replicative senescence, and serum supplements on the epigenetic makeup. Based on this, we elaborated a simple epigenetic signature based on two CpG sites to classify MSCs and fibroblasts, referred to as the Epi-MSC-Score. Another two-CpG signature can distinguish between MSCs from bone marrow and adipose tissue, referred to as the Epi-Tissue-Score. These assays were validated by site-specific pyrosequencing analysis in 34 primary cell preparations. Furthermore, even individual subclones of MSCs were correctly classified by our epigenetic signatures. In summary, we propose an alternative concept to use DNAm patterns for molecular definition of cell preparations, and our epigenetic scores facilitate robust and cost-effective quality control of MSC cultures.

  15. Concise review: mesenchymal stem cells for diabetes.

    Science.gov (United States)

    Domínguez-Bendala, Juan; Lanzoni, Giacomo; Inverardi, Luca; Ricordi, Camillo

    2012-01-01

    Mesenchymal stem cells (MSCs) have already made their mark in the young field of regenerative medicine. Easily derived from many adult tissues, their therapeutic worth has already been validated for a number of conditions. Unlike embryonic stem cells, neither their procurement nor their use is deemed controversial. Here we review the potential use of MSCs for the treatment of type 1 diabetes mellitus, a devastating chronic disease in which the insulin-producing cells of the pancreas (the β-cells) are the target of an autoimmune process. It has been hypothesized that stem cell-derived β-cells may be used to replenish the islet mass in diabetic patients, making islet transplantation (a form of cell therapy that has already proven effective at clinically restoring normoglycemia) available to millions of prospective patients. Here we review the most current advances in the design and application of protocols for the differentiation of transplantable β-cells, with a special emphasis in analyzing MSC potency according to their tissue of origin. Although no single method appears to be ripe enough for clinical trials yet, recent progress in reprogramming (a biotechnological breakthrough that relativizes the thus far insurmountable barriers between embryonal germ layers) bodes well for the rise of MSCs as a potential weapon of choice to develop personalized therapies for type 1 diabetes.

  16. Comparison of proliferative and multilineage differentiation potentials of cord matrix, cord blood, and bone marrow mesenchymal stem cells

    Directory of Open Access Journals (Sweden)

    Shetty Prathibha

    2010-01-01

    Full Text Available Background: Hematopoietic stem cells (HSCs and mesenchymal stem cells (MSCs are the two widely studied and characterized adult stem cells. Thus far, MSCs were obtained from the bone marrow, which is a painful procedure. Therefore, MSCs from less common sources like cord blood, adipose tissue, tooth pulp, and so on, have been the subject of research. The purpose of this study is to explore the possibility of finding MSCs from a less controversial, easy, and abundant source, such as the umbilical cord, for potential regenerative medicine applications. Study Design and Methods: Five bone marrow samples (BM, seventy cord blood units (CB, and four umbilical cord matrix (CM samples have been used for the study. Expanded MSCs were checked for biomarker expression by flow cytometry and were also checked for their differentiation to mesodermal and ectodermal lineages. Results: MSCs could be isolated from 100% BM and CM samples, as compared to only 6% of CB samples. The fold expansion of the mesenchymal stem cells observed in CB (CB-MSCs was distinctly higher as compared to BM (BM-MSCs and CM (CM-MSCs. MSCs isolated from all the three sources expressed a characteristic mesenchymal phenotype of CD45-/vWF-/CD14-/CD31-/CD73+/CD105+/SSEA4+/CD29+/CD44+/HLAABC+, whereas, the HLA DR was conspicuously absent in CM-MSCs and CB-MSCs. Although osteogenic, chondrogenic, and neural differentiation was observed in MSCs from all sources, adipogenic differentiation was observed only in BM-MSCs. Conclusion: CM-MSCs are a dependable source of an unlimited number of MSCs for autologous and allogenic use in regenerative medicine.

  17. Scatter factor and the c-met receptor: a paradigm for mesenchymal/epithelial interaction

    OpenAIRE

    1994-01-01

    Epithelia and mesenchyme interact during various physiologic and pathologic processes. Scatter factor is a mesenchyme-derived cytokine that stimulates motility, proliferation, and morphogenesis of epithelia. Recent studies suggest that scatter factor and its receptor (c-met) mediate mesenchyme/epithelia signalling and even interconversion. In this mini-review, we will discuss how scatter factor and c-met may mediate interactions between mesenchyme and epithelia during embryogenesis, organ rep...

  18. The neural crest and neural crest cells: discovery and significance ...

    Indian Academy of Sciences (India)

    In this paper I provide a brief overview of the major phases of investigation into the neural crest and the major players involved, discuss how the origin of the neural crest relates to the origin of the nervous system in vertebrate embryos, discuss the impact on the germ-layer theory of the discovery of the neural crest and of ...

  19. Contribution of mesenchymal proliferation in tooth root morphogenesis.

    Science.gov (United States)

    Sohn, W-J; Choi, M-A; Yamamoto, H; Lee, S; Lee, Y; Jung, J-K; Jin, M-U; An, C-H; Jung, H-S; Suh, J-Y; Shin, H-I; Kim, J-Y

    2014-01-01

    In mouse tooth development, the roots of the first lower molar develop after crown formation to form 2 cylindrical roots by post-natal day 5. This study compared the morphogenesis and cellular events of the mesial-root-forming (MRF) and bifurcation-forming (BF) regions, located in the mesial and center of the first lower molar, to better define the developmental mechanisms involved in multi-rooted tooth formation. We found that the mesenchyme in the MRF showed relatively higher proliferation than the bifurcation region. This suggested that spatially regulated mesenchymal proliferation is required for creating cylindrical root structure. The mechanism may involve the mesenchyme forming a physical barrier to epithelial invagination of Hertwig's epithelial root sheath. To test these ideas, we cultured roots in the presence of pharmacological inhibitors of microtubule and actin polymerization, nocodazole and cytochalasin-D. Cytochalasin D also inhibits proliferation in epithelium and mesenchyme. Both drugs resulted in altered morphological changes in the tooth root structures. In particular, the nocodazole- and cytochalasin-D-treated specimens showed a loss of root diameter and formation of a single-root, respectively. Immunolocalization and three-dimensional reconstruction results confirmed these mesenchymal cellular events, with higher proliferation in MRF in multi-rooted tooth formation.

  20. Concise Review: Dental Pulp Stem Cells: A Novel Cell Therapy for Retinal and Central Nervous System Repair.

    Science.gov (United States)

    Mead, Ben; Logan, Ann; Berry, Martin; Leadbeater, Wendy; Scheven, Ben A

    2017-01-01

    Dental pulp stem cells (DPSC) are neural crest-derived ecto-mesenchymal stem cells that can relatively easily and non-invasively be isolated from the dental pulp of extracted postnatal and adult teeth. Accumulating evidence suggests that DPSC have great promise as a cellular therapy for central nervous system (CNS) and retinal injury and disease. The mode of action by which DPSC confer therapeutic benefit may comprise multiple pathways, in particular, paracrine-mediated processes which involve a wide array of secreted trophic factors and is increasingly regarded as the principal predominant mechanism. In this concise review, we present the current evidence for the use of DPSC to repair CNS damage, including recent findings on retinal ganglion cell neuroprotection and regeneration in optic nerve injury and glaucoma. Stem Cells 2017;35:61-67. © 2016 AlphaMed Press.

  1. Cell fate determination during tooth development and regeneration.

    Science.gov (United States)

    Mitsiadis, Thimios A; Graf, Daniel

    2009-09-01

    Teeth arise from sequential and reciprocal interactions between the oral epithelium and the underlying cranial neural crest-derived mesenchyme. Their formation involves a precisely orchestrated series of molecular and morphogenetic events, and gives us the opportunity to discover and understand the nature of the signals that direct cell fates and patterning. For that reason, it is important to elucidate how signaling factors work together in a defined number of cells to generate the diverse and precise patterned structures of the mature functional teeth. Over the last decade, substantial research efforts have been directed toward elucidating the molecular mechanisms that control cell fate decisions during tooth development. These efforts have contributed toward the increased knowledge on dental stem cells, and observation of the molecular similarities that exist between tooth development and regeneration.

  2. Introduction to Artificial Neural Networks

    DEFF Research Database (Denmark)

    Larsen, Jan

    1999-01-01

    The note addresses introduction to signal analysis and classification based on artificial feed-forward neural networks.......The note addresses introduction to signal analysis and classification based on artificial feed-forward neural networks....

  3. Deconvolution using a neural network

    Energy Technology Data Exchange (ETDEWEB)

    Lehman, S.K.

    1990-11-15

    Viewing one dimensional deconvolution as a matrix inversion problem, we compare a neural network backpropagation matrix inverse with LMS, and pseudo-inverse. This is a largely an exercise in understanding how our neural network code works. 1 ref.

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  18. Glial origin of mesenchymal stem cells in a tooth model system

    NARCIS (Netherlands)

    Kaukua, Nina; Shahidi, Maryam Khatibi; Konstantinidou, Chrysoula; Dyachuk, Vyacheslav; Kaucka, Marketa; Furlan, Alessandro; An, Zhengwen; Wang, Longlong; Hultman, Isabell; Ahrlund-Richter, Lars; Blom, Hans; Brismar, Hjalmar; Lopes, Natalia Assaife; Pachnis, Vassilis; Suter, Ueli; Clevers, Hans; Thesleff, Irma; Sharpe, Paul; Ernfors, Patrik; Fried, Kaj; Adameyko, Igor

    2014-01-01

    Mesenchymal stem cells occupy niches in stromal tissues where they provide sources of cells for specialized mesenchymal derivatives during growth and repair. The origins of mesenchymal stem cells have been the subject of considerable discussion, and current consensus holds that perivascular cells

  19. Interferon-γ regulates the proliferation and differentiation of mesenchymal stem cells via activation of indoleamine 2,3 dioxygenase (IDO.

    Directory of Open Access Journals (Sweden)

    Juliana Croitoru-Lamoury

    Full Text Available The kynurenine pathway (KP of tryptophan metabolism is linked to antimicrobial activity and modulation of immune responses but its role in stem cell biology is unknown. We show that human and mouse mesenchymal and neural stem cells (MSCs and NSCs express the complete KP, including indoleamine 2,3 dioxygenase 1 (IDO and IDO2, that it is highly regulated by type I (IFN-β and II interferons (IFN-γ, and that its transcriptional modulation depends on the type of interferon, cell type and species. IFN-γ inhibited proliferation and altered human and mouse MSC neural, adipocytic and osteocytic differentiation via the activation of IDO. A functional KP present in MSCs, NSCs and perhaps other stem cell types offers novel therapeutic opportunities for optimisation of stem cell proliferation and differentiation.

  20. Human Mesenchymal Stem Cells Derived From Limb Bud Can Differentiate into All Three Embryonic Germ Layers Lineages

    Science.gov (United States)

    Jiao, Fei; Wang, Juan; Dong, Zhao-lun; Wu, Min-juan; Zhao, Ting-bao; Li, Dan-dan

    2012-01-01

    Abstract Mesenchymal stem cells (MSCs) have been isolated from many sources, including adults and fetuses. Previous studies have demonstrated that, compared with their adult counterpart, fetal MSCs with several remarkable advantages may be a better resource for clinical applications. In this study, we successfully isolated a rapidly proliferating cell population from limb bud of aborted fetus and termed them “human limb bud–derived mesenchymal stem cells” (hLB-MSCs). Characteristics of their morphology, phenotype, cell cycle, and differentiation properties were analyzed. These adherent cell populations have a typically spindle-shaped morphology. Flow cytometry analysis showed that hLB-MSCs are positive for CD13, CD29, CD90, CD105, and CD106, but negative for CD3, CD4, CD5, CD11b, CD14, CD15, CD34, CD45, CD45RA, and HLA-DR. The detection of cell cycle from different passages indicated that hLB-MSCs have a similar potential for propagation during long culture in vitro. The most novel finding here is that, in addition to their mesodermal differentiation (osteoblasts and adipocytes), hLB-MSCs can also differentiated into extramesenchymal lineages, such as neural (ectoderm) and hepatic (endoderm) progenies. These results indicate that hLB-MSCs have a high level of plasticity and can differentiate into cell lineages from all three embryonic layers in vitro. PMID:22775353

  1. Mesenchymal Stem Cells and the Origin of Ewing's Sarcoma

    Directory of Open Access Journals (Sweden)

    Patrick P. Lin

    2011-01-01

    Full Text Available The origin of Ewing's sarcoma is a subject of much debate. Once thought to be derived from primitive neuroectodermal cells, many now believe it to arise from a mesenchymal stem cell (MSC. Expression of the EWS-FLI1 fusion gene in MSCs changes cell morphology to resemble Ewing's sarcoma and induces expression of neuroectodermal markers. In murine cells, transformation to sarcomas can occur. In knockdown experiments, Ewing's sarcoma cells develop characteristics of MSCs and the ability to differentiate into mesodermal lineages. However, it cannot be concluded that MSCs are the cell of origin. The concept of an MSC still needs to be rigorously defined, and there may be different subpopulations of mesenchymal pluripotential cells. Furthermore, EWS-FLI1 by itself does not transform human cells, and cooperating mutations appear to be necessary. Therefore, while it is possible that Ewing's sarcoma may originate from a primitive mesenchymal cell, the idea needs to be refined further.

  2. The role of endothelial-mesenchymal transition in heterotopic ossification

    Science.gov (United States)

    Medici, Damian; Olsen, Bjorn R.

    2012-01-01

    Heterotopic ossification (HO) is a process by which bone forms in soft tissues, in response to injury, inflammation or genetic disease. This usually occurs by initial cartilage formation, followed by endochondral ossification. A rare disease called Fibrodysplasia Ossificans Progressiva (FOP) allows this mechanism to be induced by a combination of genetic mutation and acute inflammatory responses. FOP patients experience progressive HO throughout their lifetime and form an ectopic skeleton. Recent studies on FOP have suggested that heterotopic cartilage and bone is of endothelial origin. Vascular endothelial cells differentiate into skeletal cells through a mesenchymal stem cell intermediate that is generated by endothelial-mesenchymal transition (EndMT). Local inflammatory signals and/or other changes in the tissue microenvironment mediate the differentiation of endothelial-derived mesenchymal stem cells into chondrocytes and osteoblasts to induce HO. Here we discuss the current evidence for the endothelial contribution to heterotopic bone formation. PMID:22806925

  3. Extraskeletal Intracranial Mesenchymal Chondrosarcoma: Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Jun-Yih Chen

    2004-05-01

    Full Text Available We present the case of a 13-year-old girl with a huge intracranial mesenchymal chondrosarcoma. She had suffered from severe headache, diplopia, intermittent nausea and vomiting for 1 month. Neurologic examination revealed bilateral blurred optic disc margins and abducens paresis. Magnetic resonance imaging demonstrated a giant, heterogeneous, intensely enhancing mass of 7 × 8 × 6 cm, occupying the bilateral frontal and left high parietal regions and based on the anterior cerebral falx. A presumptive diagnosis of aggressive meningioma was made. The patient underwent bicoronal craniotomy and gross total resection of the tumor. Pathologic examination revealed an extraskeletal mesenchymal chondrosarcoma. She was under regular follow-up and remained free of recurrence after surgery. In addition to the current case, we review previously reported cases of extraskeletal intracranial mesenchymal chondrosarcoma and discuss treatment strategies and outcomes.

  4. Neural Network Ensembles

    DEFF Research Database (Denmark)

    Hansen, Lars Kai; Salamon, Peter

    1990-01-01

    We propose several means for improving the performance an training of neural networks for classification. We use crossvalidation as a tool for optimizing network parameters and architecture. We show further that the remaining generalization error can be reduced by invoking ensembles of similar...... networks....

  5. Neural systems for control

    National Research Council Canada - National Science Library

    Omidvar, Omid; Elliott, David L

    1997-01-01

    ... is reprinted with permission from A. Barto, "Reinforcement Learning," Handbook of Brain Theory and Neural Networks, M.A. Arbib, ed.. The MIT Press, Cambridge, MA, pp. 804-809, 1995. Chapter 4, Figures 4-5 and 7-9 and Tables 2-5, are reprinted with permission, from S. Cho, "Map Formation in Proprioceptive Cortex," International Jour...

  6. Neural Tube Defects

    Science.gov (United States)

    ... pregnancies each year in the United States. A baby’s neural tube normally develops into the brain and spinal cord. ... fluid in the brain. This is called hydrocephalus. Babies with this condition are treated with surgery to insert a tube (called a shunt) into the brain. The shunt ...

  7. A role for mesenchyme dynamics in mouse lung branching morphogenesis.

    Directory of Open Access Journals (Sweden)

    Pierre Blanc

    Full Text Available Mammalian airways are highly ramified tree-like structures that develop by the repetitive branching of the lung epithelium into the surrounding mesenchyme through reciprocal interactions. Based on a morphometric analysis of the epithelial tree, it has been recently proposed that the complete branching scheme is specified early in each lineage by a programme using elementary patterning routines at specific sites and times in the developing lung. However, the coupled dynamics of both the epithelium and mesenchyme have been overlooked in this process. Using a qualitative and quantitative in vivo morphometric analysis of the E11.25 to E13.5 mouse whole right cranial lobe structure, we show that beyond the first generations, the branching stereotypy relaxes and both spatial and temporal variations are common. The branching pattern and branching rate are sensitive to the dynamic changes of the mesoderm shape that is in turn mainly dependent upon the volume and shape of the surrounding intrathoracic organs. Spatial and temporal variations of the tree architecture are related to local and subtle modifications of the mesoderm growth. Remarkably, buds never meet after suffering branching variations and continue to homogenously fill the opening spaces in the mesenchyme. Moreover despite inter-specimen variations, the growth of the epithelial tree and the mesenchyme remains highly correlated over time at the whole lobe level, implying a long-range regulation of the lung lobe morphogenesis. Together, these findings indicate that the lung epithelial tree is likely to adapt in real time to fill the available space in the mesenchyme, rather than being rigidly specified and predefined by a global programme. Our results strongly support the idea that a comprehensive understanding of lung branching mechanisms cannot be inferred from the branching pattern or behavior alone. Rather it needs to be elaborated upon with the reconsideration of mesenchyme

  8. Augmented BMPRIA-mediated BMP signaling in cranial neural crest lineage leads to cleft palate formation and delayed tooth differentiation.

    Directory of Open Access Journals (Sweden)

    Lu Li

    Full Text Available The importance of BMP receptor Ia (BMPRIa mediated signaling in the development of craniofacial organs, including the tooth and palate, has been well illuminated in several mouse models of loss of function, and by its mutations associated with juvenile polyposis syndrome and facial defects in humans. In this study, we took a gain-of-function approach to further address the role of BMPR-IA-mediated signaling in the mesenchymal compartment during tooth and palate development. We generated transgenic mice expressing a constitutively active form of BmprIa (caBmprIa in cranial neural crest (CNC cells that contributes to the dental and palatal mesenchyme. Mice bearing enhanced BMPRIa-mediated signaling in CNC cells exhibit complete cleft palate and delayed odontogenic differentiation. We showed that the cleft palate defect in the transgenic animals is attributed to an altered cell proliferation rate in the anterior palatal mesenchyme and to the delayed palatal elevation in the posterior portion associated with ectopic cartilage formation. Despite enhanced activity of BMP signaling in the dental mesenchyme, tooth development and patterning in transgenic mice appeared normal except delayed odontogenic differentiation. These data support the hypothesis that a finely tuned level of BMPRIa-mediated signaling is essential for normal palate and tooth development.

  9. Mesenchymal Stromal Cell Therapy in Crohn's Disease.

    Science.gov (United States)

    Forbes, Geoffrey M

    2017-01-01

    Mesenchymal stromal cells (MSC) are multipotent adult stem cells with immunomodulatory properties. They uniquely express HLA class I antigen at a low level, and do not express HLA class II. Hence, for allogeneic administration, donor to recipient matching is not required; yet a prolonged chimeric state does not occur. Contrary to haematopoietic stem cell transplantation, cytotoxic drug therapy is not required to harvest, or administer, cells. Key Messages: MSC are obtained from marrow, adipose tissue or placenta. In our centre, MSC are isolated from a 10 ml donor marrow aspirate, by virtue of their adherence to plastic. They are expanded in culture, cryopreserved, and subjected to strict quality controls before release for intravenous administration. These activities occur in a dedicated, nationally accredited, laboratory. Initial observations of allogeneic MSC efficacy were in graft-versus-host disease. Both autologous and allogeneic MSC have since been evaluated in biologic refractory luminal and fistulising Crohn's disease (CD). Data from early-phase studies have suggested efficacy for luminal disease when allogeneic MSC were given intravenously and also suggested efficacy for fistulising disease when either allogeneic or autologous MSC were administered into fistulas. MSC treatment is not reported to have caused serious adverse events. Although in vitro criteria for defining MSC exist, a major challenge lies in how to define MSC for clinical use. MSC function in vivo is likely to be dependent upon donor immunological characteristics, and widely varying manufacturing processes between laboratories. MSC dose, frequency of administration, stage of disease, and presence of concomitant immunosuppression also require to be defined. MSC therapy may have future utility in CD, but considerable work is first required to determine appropriate phenotypic and functional characteristics of administered cells. © 2017 S. Karger AG, Basel.

  10. Quantum dot labeling of mesenchymal stem cells

    Directory of Open Access Journals (Sweden)

    Cascio Wayne E

    2007-11-01

    Full Text Available Abstract Background Mesenchymal stem cells (MSCs are multipotent cells with the potential to differentiate into bone, cartilage, fat and muscle cells and are being investigated for their utility in cell-based transplantation therapy. Yet, adequate methods to track transplanted MSCs in vivo are limited, precluding functional studies. Quantum Dots (QDs offer an alternative to organic dyes and fluorescent proteins to label and track cells in vitro and in vivo. These nanoparticles are resistant to chemical and metabolic degradation, demonstrating long term photostability. Here, we investigate the cytotoxic effects of in vitro QD labeling on MSC proliferation and differentiation and use as a cell label in a cardiomyocyte co-culture. Results A dose-response to QDs in rat bone marrow MSCs was assessed in Control (no-QDs, Low concentration (LC, 5 nmol/L and High concentration (HC, 20 nmol/L groups. QD yield and retention, MSC survival, proinflammatory cytokines, proliferation and DNA damage were evaluated in MSCs, 24 -120 hrs post QD labeling. In addition, functional integration of QD labeled MSCs in an in vitro cardiomyocyte co-culture was assessed. A dose-dependent effect was measured with increased yield in HC vs. LC labeled MSCs (93 ± 3% vs. 50% ± 15%, p 90% of QD labeled cells were viable in all groups, however, at 120 hrs increased apoptosis was measured in HC vs. Control MSCs (7.2% ± 2.7% vs. 0.5% ± 0.4%, p Conclusion Fluorescent QDs label MSC effectively in an in vitro co-culture model. QDs are easy to use, show a high yield and survival rate with minimal cytotoxic effects. Dose-dependent effects suggest limiting MSC QD exposure.

  11. Nanoscale Mechanical Stimulation of Human Mesenchymal Stem Cells

    Directory of Open Access Journals (Sweden)

    H Nikukar

    2014-05-01

    We observed significant responses after 1 and 2-week stimulations in cell number, cell shapes and phenotypical markers. Microarray was performed for all groups. Cell count showed normal cell growth with stimulation. However, cell surface area, cell perimeter, and arboration after 1-week stimulation showed significant increases. Immunofluorescent studies have showed significant increase in osteocalcin production after stimulation. Conclusions: Nanoscale mechanical vibration showed significant changes in human mesenchymal stem cell behaviours. Cell morphology changed to become more polygonal and increased expression of the osteoblast markers were noted. These findings with gene regulation changes suggesting nanoscale mechanostimulation has stimulated osteoblastogenesis.  Keywords:  Mesenchymal, Nanoscale, Stem Cells.

  12. [Rare mesenchymal lesions in siblings. Two case reports].

    Science.gov (United States)

    Guschmann, M; Frege, J; Lübbert, E; Golla, S; Rudolph, B; Haake, K; Stöver, B

    2003-05-01

    We report on a 15-month-old boy presenting a juvenile active ossifying fibroma in the right nasal cavity and the sibling, a 9-month-old girl with a mesenchymal hamartoma of the chest wall. The two lesions showed many similarities. Both lesions are present at the time of birth or in early life with local obstructive or compressive effects. The lesions have a similar mixture of mature and immature mesenchymal tissue with areas of ossification. The entities present a tumor-like development with an abnormal mixture of tissue indigenous to the specific area of the body without notable atypical cytologic features. These features are typical criteria for hamartoma lesions.

  13. Mesenchymal Stromal Cells: Updates and Therapeutic Outlook in Rheumatic Diseases

    Directory of Open Access Journals (Sweden)

    Christian Jorgensen

    2013-10-01

    Full Text Available Multipotent mesenchymal stromal cells or mesenchymal stem cells (MSCs are adult stem cells exhibiting functional properties that have opened the way for cell-based clinical therapies. MSCs have been reported to exhibit immunosuppressive as well as healing properties, improving angiogenesis and preventing apoptosis or fibrosis through the secretion of paracrine mediators. This review summarizes recent progress on the clinical application of stem cells therapy in some inflammatory and degenerative rheumatic diseases. To date, most of the available data have been obtained in preclinical models and clinical efficacy needs to be evaluated through controlled randomized double-blind trials.

  14. Primary intradural mesenchymal chondrosarcoma of the spine in a child

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yu-Hua [Shanghai Jiao Tong University, Department of Radiology, Xin Hua Hospital, School of Medicine, Shanghai (China); Yao, Xiao-Hong [Shanghai Jiao Tong University, Department of Pathology, Xin Hua Hospital, School of Medicine, Shanghai (China)

    2007-11-15

    We report a primary intradural mesenchymal chondrosarcoma of the spine in a 3-year-old girl. MRI revealed a markedly enhancing oval mass associated with focal areas of low signal intensity extending from T11 to L1. The lesion was located posterolateral to the right side of the spinal cord, pushing the conus medullaris and cauda equina anteriorly and to the left. The adjacent spinal cord also showed serpiginous areas of flow void. The mass was completely removed. Microscopic examination and immunohistochemical studies confirmed the diagnosis of mesenchymal chondrosarcoma. The patient was free of symptoms after surgery. (orig.)

  15. Mesenchymal Stem Cells Improve Healing of Diabetic Foot Ulcer

    Directory of Open Access Journals (Sweden)

    Yue Cao

    2017-01-01

    Full Text Available Mesenchymal stem cells (MSCs, an ideal cell source for regenerative therapy with no ethical issues, play an important role in diabetic foot ulcer (DFU. Growing evidence has demonstrated that MSCs transplantation can accelerate wound closure, ameliorate clinical parameters, and avoid amputation. In this review, we clarify the mechanism of preclinical studies, as well as safety and efficacy of clinical trials in the treatment of DFU. Bone marrow-derived mesenchymal stem cells (BM-MSCs, compared with MSCs derived from other tissues, may be a suitable cell type that can provide easy, effective, and cost-efficient transplantation to treat DFU and protect patients from amputation.

  16. Bioprinting for Neural Tissue Engineering.

    Science.gov (United States)

    Knowlton, Stephanie; Anand, Shivesh; Shah, Twisha; Tasoglu, Savas

    2018-01-01

    Bioprinting is a method by which a cell-encapsulating bioink is patterned to create complex tissue architectures. Given the potential impact of this technology on neural research, we review the current state-of-the-art approaches for bioprinting neural tissues. While 2D neural cultures are ubiquitous for studying neural cells, 3D cultures can more accurately replicate the microenvironment of neural tissues. By bioprinting neuronal constructs, one can precisely control the microenvironment by specifically formulating the bioink for neural tissues, and by spatially patterning cell types and scaffold properties in three dimensions. We review a range of bioprinted neural tissue models and discuss how they can be used to observe how neurons behave, understand disease processes, develop new therapies and, ultimately, design replacement tissues. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Transplantation of neuronal-primed human bone marrow mesenchymal stem cells in hemiparkinsonian rodents.

    Science.gov (United States)

    Khoo, Melissa L M; Tao, Helen; Meedeniya, Adrian C B; Mackay-Sim, Alan; Ma, David D F

    2011-01-01

    Bone marrow-derived human mesenchymal stem cells (hMSCs) have shown promise in in vitro neuronal differentiation and in cellular therapy for neurodegenerative disorders, including Parkinson' disease. However, the effects of intracerebral transplantation are not well defined, and studies do not agreed on the optimal neuronal differentiation method. Here, we investigated three growth factor-based neuronal differentiation procedures (using FGF-2/EGF/PDGF/SHH/FGF-8/GDNF), and found all to be capable of eliciting an immature neural phenotype, in terms of cell morphology and gene/protein expression. The neuronal-priming (FGF-2/EGF) method induced neurosphere-like formation and the highest NES and NR4A2 expression by hMSCs. Transplantation of undifferentiated and neuronal-primed hMSCs into the striatum and substantia nigra of 6-OHDA-lesioned hemiparkinsonian rats revealed transient graft survival of 7 days, despite the reported immunosuppressive properties of MSCs and cyclosporine-immunosuppression of rats. Neither differentiation of hMSCs nor induction of host neurogenesis was observed at injection sites, and hMSCs continued producing mesodermal fibronectin. Strategies for improving engraftment and differentiation post-transplantation, such as prior in vitro neuronal-priming, nigral and striatal grafting, and co-transplantation of olfactory ensheathing cells that promote neural regeneration, were unable to provide advantages. Innate inflammatory responses (Iba-1-positive microglia/macrophage and GFAP-positive astrocyte activation and accumulation) were detected around grafts within 7 days. Our findings indicate that growth factor-based methods allow hMSC differentiation toward immature neuronal-like cells, and contrary to previous reports, only transient survival and engraftment of hMSCs occurs following transplantation in immunosuppressed hemiparkinsonian rats. In addition, suppression of host innate inflammatory responses may be a key factor for improving hMSC survival

  18. Making headway: the roles of Hox genes and neural crest cells in craniofacial development.

    Science.gov (United States)

    Trainor, Paul A

    2003-04-14

    Craniofacial development is an extraordinarily complex process requiring the orchestrated integration of multiple specialized tissues such as the surface ectoderm, neural crest, mesoderm, and pharyngeal endoderm in order to generate the central and peripheral nervous systems, axial skeleton, musculature, and connective tissues of the head and face. How do the characteristic facial structures develop in the appropriate locations with their correct shapes and sizes, given the widely divergent patterns of cell movements that occur during head development? The patterning information could depend upon localized interactions between the epithelial and mesenchymal tissues or alternatively, the developmental program for the characteristic facial structures could be intrinsic to each individual tissue precursor. Understanding the mechanisms that control vertebrate head development is an important issue since craniofacial anomalies constitute nearly one third of all human congenital defects. This review discusses recent advances in our understanding of neural crest cell patterning and the dynamic nature of the tissue interactions that are required for normal craniofacial development.

  19. Early Determination of the Periodontal Domain by the Wnt-Antagonist Frzb/Sfrp3

    Directory of Open Access Journals (Sweden)

    Thimios A. Mitsiadis

    2017-11-01

    Full Text Available Odontogenesis results from the continuous and reciprocal interaction between cells of the oral epithelium and cranial neural crest-derived mesenchyme. The canonical Wnt signaling pathway plays a fundamental role in mediating these interactions from the earliest stages of tooth development. Here we analyze by in situ hybridization the expression patterns of the extracellular Wnt antagonist Frzb/Sfrp3. Although Frzb is expressed in dental mesenchymal cells from the earliest stages of odontogenesis, its expression is absent from a tiny population of mesenchymal cells immediately adjacent to the invaginating dental epithelium. Cell proliferation studies using BrdU showed that the Frzb expressing and Frzb non-expressing cell populations display different proliferative behavior during the initial stages of odontogenesis. DiI-mediated cell-fate tracing studies demonstrated that the Frzb expressing cells contribute to the formation of the dental follicle, the future periodontium. In contrast, the Frzb non-expressing cells give rise to the dental pulp. The present results indicate that Frzb is discriminating the presumptive periodontal territory from the rest of the dental mesenchyme from the very beginning of odontogenesis, where it might act as a barrier for the diffusion of Wnt molecules, thus regulating the activation of Wnt-dependent transcription within dental tissues.

  20. Lhx8 mediated Wnt and TGFβ pathways in tooth development and regeneration.

    Science.gov (United States)

    Zhou, Chen; Yang, Guodong; Chen, Mo; Wang, Chenglin; He, Ling; Xiang, Lusai; Chen, Danying; Ling, Junqi; Mao, Jeremy J

    2015-09-01

    LIM homeobox 8 (Lhx8) is a highly conserved transcriptional factor with recently illustrated roles in cholinergic and GABAergic differentiation, and is expressed in neural crest derived craniofacial tissues during development. However, Lhx8 functions and signaling pathways are largely elusive. Here we showed that Lhx8 regulates dental mesenchyme differentiation and function via Wnt and TGFβ pathways. Lhx8 expression was restricted to dental mesenchyme from E11.5 to a peak at E14.5, and absent in dental epithelium. By reconstituting dental epithelium and mesenchyme in an E16.5 tooth organ, Lhx8 knockdown accelerated dental mesenchyme differentiation; conversely, Lhx8 overexpression attenuated dentin formation. Lhx8 overexpressed adult human dental pulp stem/progenitor cells in β-tricalcium phosphate cubes attenuated mineralized matrix production in vivo. Gene profiling revealed that postnatal dental pulp stem/progenitor cells upon Lhx8 overexpression modified matrix related gene expression including Dspp, Cola1 and osteocalcin. Lhx8 transcriptionally activated Wnt and TGFβ pathways, and its attenuation upregulated multiple dentinogenesis genes. Together, Lhx8 regulates dentin development and regeneration by fine-turning Wnt and TGFβ signaling. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Early Determination of the Periodontal Domain by the Wnt-Antagonist Frzb/Sfrp3

    Science.gov (United States)

    Mitsiadis, Thimios A.; Pagella, Pierfrancesco; Cantù, Claudio

    2017-01-01

    Odontogenesis results from the continuous and reciprocal interaction between cells of the oral epithelium and cranial neural crest-derived mesenchyme. The canonical Wnt signaling pathway plays a fundamental role in mediating these interactions from the earliest stages of tooth development. Here we analyze by in situ hybridization the expression patterns of the extracellular Wnt antagonist Frzb/Sfrp3. Although Frzb is expressed in dental mesenchymal cells from the earliest stages of odontogenesis, its expression is absent from a tiny population of mesenchymal cells immediately adjacent to the invaginating dental epithelium. Cell proliferation studies using BrdU showed that the Frzb expressing and Frzb non-expressing cell populations display different proliferative behavior during the initial stages of odontogenesis. DiI-mediated cell-fate tracing studies demonstrated that the Frzb expressing cells contribute to the formation of the dental follicle, the future periodontium. In contrast, the Frzb non-expressing cells give rise to the dental pulp. The present results indicate that Frzb is discriminating the presumptive periodontal territory from the rest of the dental mesenchyme from the very beginning of odontogenesis, where it might act as a barrier for the diffusion of Wnt molecules, thus regulating the activation of Wnt-dependent transcription within dental tissues. PMID:29209231

  2. Stem Cells in Tooth Development, Growth, Repair, and Regeneration.

    Science.gov (United States)

    Yu, Tian; Volponi, Ana Angelova; Babb, Rebecca; An, Zhengwen; Sharpe, Paul T

    2015-01-01

    Human teeth contain stem cells in all their mesenchymal-derived tissues, which include the pulp, periodontal ligament, and developing roots, in addition to the support tissues such as the alveolar bone. The precise roles of these cells remain poorly understood and most likely involve tissue repair mechanisms but their relative ease of harvesting makes teeth a valuable potential source of mesenchymal stem cells (MSCs) for therapeutic use. These dental MSC populations all appear to have the same developmental origins, being derived from cranial neural crest cells, a population of embryonic stem cells with multipotential properties. In rodents, the incisor teeth grow continuously throughout life, a feature that requires populations of continuously active mesenchymal and epithelial stem cells. The discrete locations of these stem cells in the incisor have rendered them amenable for study and much is being learnt about the general properties of these stem cells for the incisor as a model system. The incisor MSCs appear to be a heterogeneous population consisting of cells from different neural crest-derived tissues. The epithelial stem cells can be traced directly back in development to a Sox10(+) population present at the time of tooth initiation. In this review, we describe the basic biology of dental stem cells, their functions, and potential clinical uses. © 2015 Elsevier Inc. All rights reserved.

  3. Neural network technologies

    Science.gov (United States)

    Villarreal, James A.

    1991-01-01

    A whole new arena of computer technologies is now beginning to form. Still in its infancy, neural network technology is a biologically inspired methodology which draws on nature's own cognitive processes. The Software Technology Branch has provided a software tool, Neural Execution and Training System (NETS), to industry, government, and academia to facilitate and expedite the use of this technology. NETS is written in the C programming language and can be executed on a variety of machines. Once a network has been debugged, NETS can produce a C source code which implements the network. This code can then be incorporated into other software systems. Described here are various software projects currently under development with NETS and the anticipated future enhancements to NETS and the technology.

  4. Analysis of neural data

    CERN Document Server

    Kass, Robert E; Brown, Emery N

    2014-01-01

    Continual improvements in data collection and processing have had a huge impact on brain research, producing data sets that are often large and complicated. By emphasizing a few fundamental principles, and a handful of ubiquitous techniques, Analysis of Neural Data provides a unified treatment of analytical methods that have become essential for contemporary researchers. Throughout the book ideas are illustrated with more than 100 examples drawn from the literature, ranging from electrophysiology, to neuroimaging, to behavior. By demonstrating the commonality among various statistical approaches the authors provide the crucial tools for gaining knowledge from diverse types of data. Aimed at experimentalists with only high-school level mathematics, as well as computationally-oriented neuroscientists who have limited familiarity with statistics, Analysis of Neural Data serves as both a self-contained introduction and a reference work.

  5. Neural tube defects

    Directory of Open Access Journals (Sweden)

    M.E. Marshall

    1981-09-01

    Full Text Available Neural tube defects refer to any defect in the morphogenesis of the neural tube, the most common types being spina bifida and anencephaly. Spina bifida has been recognised in skeletons found in north-eastern Morocco and estimated to have an age of almost 12 000 years. It was also known to the ancient Greek and Arabian physicians who thought that the bony defect was due to the tumour. The term spina bifida was first used by Professor Nicolai Tulp of Amsterdam in 1652. Many other terms have been used to describe this defect, but spina bifida remains the most useful general term, as it describes the separation of the vertebral elements in the midline.

  6. Electro-Acupuncture Promotes Endogenous Multipotential Mesenchymal Stem Cell Mobilization into the Peripheral Blood.

    Science.gov (United States)

    Liu, Lizhen; Yu, Qin; Hu, Kaimin; Wang, Binsheng; Zhang, Yiran; Xu, Yulin; Fu, Shan; Yu, Xiaohong; Huang, He

    2016-01-01

    Mobilization of endogenous stem cells is an appealing strategy for cell therapy However, there is little evidence for reproducible, effective methods of mesenchymal stem cell (MSC) mobilization. In the present study, we investigated the mobilizing effect of electro-acupuncture (EA) on endogenous MSCs. Normal adult rats were randomly divided into six groups, namely, EA for 14 days (EA14d), sham EA14d, EA21d, sham EA21d and matched control groups. MSC mobilization efficiency was determined by colony-forming unit fibroblast (CFU-F) assays. Mobilized peripheral blood (PB)-derived MSCs were identified by immunophenotype and multi-lineage differentiation potential. CFU-F frequency was significantly increased in the PB of EA14d rats compared with the sham EA and control groups. Moreover, the number of CFU-Fs was increased further in the EA21d group. MSCs derived from EA-mobilized PB were positive for CD90 and CD44, but negative for CD45. Additionally, these cells could differentiate into adipocytes, osteoblasts, chondrocytes and neural-like cells in vitro. Finally, stromal cell-derived factor-1α (SDF-1α) was increased in the PB of rats subjected to EA, and the migration of MSCs was improved in response to SDF-1α. MSCs with multi-lineage differentiation potential can be mobilized by EA. Our data provide a promising strategy for MSC mobilization. © 2016 The Author(s) Published by S. Karger AG, Basel.

  7. Electro-Acupuncture Promotes Endogenous Multipotential Mesenchymal Stem Cell Mobilization into the Peripheral Blood

    Directory of Open Access Journals (Sweden)

    Lizhen Liu

    2016-04-01

    Full Text Available Background/Aims: Mobilization of endogenous stem cells is an appealing strategy for cell therapy However, there is little evidence for reproducible, effective methods of mesenchymal stem cell (MSC mobilization. In the present study, we investigated the mobilizing effect of electro-acupuncture (EA on endogenous MSCs. Methods: Normal adult rats were randomly divided into six groups, namely, EA for 14 days (EA14d, sham EA14d, EA21d, sham EA21d and matched control groups. MSC mobilization efficiency was determined by colony-forming unit fibroblast (CFU-F assays. Mobilized peripheral blood (PB-derived MSCs were identified by immunophenotype and multi-lineage differentiation potential. Results: CFU-F frequency was significantly increased in the PB of EA14d rats compared with the sham EA and control groups. Moreover, the number of CFU-Fs was increased further in the EA21d group. MSCs derived from EA-mobilized PB were positive for CD90 and CD44, but negative for CD45. Additionally, these cells could differentiate into adipocytes, osteoblasts, chondrocytes and neural-like cells in vitro. Finally, stromal cell-derived factor-1α (SDF-1α was increased in the PB of rats subjected to EA, and the migration of MSCs was improved in response to SDF-1α. Conclusions: MSCs with multi-lineage differentiation potential can be mobilized by EA. Our data provide a promising strategy for MSC mobilization.

  8. Cannabidiol Activates Neuronal Precursor Genes in Human Gingival Mesenchymal Stromal Cells.

    Science.gov (United States)

    Soundara Rajan, Thangavelu; Giacoppo, Sabrina; Scionti, Domenico; Diomede, Francesca; Grassi, Gianpaolo; Pollastro, Federica; Piattelli, Adriano; Bramanti, Placido; Mazzon, Emanuela; Trubiani, Oriana

    2017-06-01

    In the last years, mesenchymal stromal cells (MSCs) from oral tissues have received considerable interest in regenerative medicine since they can be obtained with minimal invasive procedure and exhibit immunomodulatory properties. This study was aimed to investigate whether in vitro pre-treatment of MSCs obtained from human gingiva (hGMSCs) with Cannabidiol (CBD), a cannabinoid component produced by the plant Cannabis sativa, may promote human gingiva derived MSCs to differentiate toward neuronal precursor cells. Specifically, we have treated the hGMSCs with CBD (5 µM) for 24 h in order to evaluate the expression of genes involved in cannabidiol signaling, cell proliferation, self-renewal and multipotency, and neural progenitor cells differentiation. Next generation sequencing (NGS) demonstrated that CBD activates genes associated with G protein coupled receptor signaling in hGMSCs. Genes involved in DNA replication, cell cycle, proliferation, and apoptosis were regulated. Moreover, genes associated with the biological process of neuronal progenitor cells (NCPs) proliferation, neuron differentiation, neurogenesis, and nervous system development were significantly modulated. From our results, we hypothesize that human gingiva-derived MSCs conditioned with CBD could represent a valid method for improving the hGMSCs phenotype and thus might be a potential therapeutic tool in the treatment of neurodegenerative diseases. J. Cell. Biochem. 118: 1531-1546, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  9. Adipose-Derived Mesenchymal Stromal/Stem Cells: Tissue Localization, Characterization, and Heterogeneity

    Directory of Open Access Journals (Sweden)

    Patrick C. Baer

    2012-01-01

    Full Text Available Adipose tissue as a stem cell source is ubiquitously available and has several advantages compared to other sources. It is easily accessible in large quantities with minimal invasive harvesting procedure, and isolation of adipose-derived mesenchymal stromal/stem cells (ASCs yields a high amount of stem cells, which is essential for stem-cell-based therapies and tissue engineering. Several studies have provided evidence that ASCs in situ reside in a perivascular niche, whereas the exact localization of ASCs in native adipose tissue is still under debate. ASCs are isolated by their capacity to adhere to plastic. Nevertheless, recent isolation and culture techniques lack standardization. Cultured cells are characterized by their expression of characteristic markers and their capacity to differentiate into cells from meso-, ecto-, and entodermal lineages. ASCs possess a high plasticity and differentiate into various cell types, including adipocytes, osteoblasts, chondrocytes, myocytes, hepatocytes, neural cells, and endothelial and epithelial cells. Nevertheless, recent studies suggest that ASCs are a heterogeneous mixture of cells containing subpopulations of stem and more committed progenitor cells. This paper summarizes and discusses the current knowledge of the tissue localization of ASCs in situ, their characterization and heterogeneity in vitro, and the lack of standardization in isolation and culture methods.

  10. Secretome of Olfactory Mucosa Mesenchymal Stem Cell, a Multiple Potential Stem Cell

    Directory of Open Access Journals (Sweden)

    Lite Ge

    2016-01-01

    Full Text Available Nasal olfactory mucosa mesenchymal stem cells (OM-MSCs have the ability to promote regeneration in the nervous system in vivo. Moreover, with view to the potential for clinical application, OM-MSCs have the advantage of being easily accessible from patients and transplantable in an autologous manner, thus eliminating immune rejection and contentious ethical issues. So far, most studies have been focused on the role of OM-MSCs in central nervous system replacement. However, the secreted proteomics of OM-MSCs have not been reported yet. Here, proteins secreted by OM-MSCs cultured in serum-free conditions were separated on SDS-PAGE and identified by LC-MS/MS. As a result, a total of 274 secreted proteins were identified. These molecules are known to be important in neurotrophy, angiogenesis, cell growth, differentiation, and apoptosis, and inflammation which were highly correlated with the repair of central nervous system. The proteomic profiling of the OM-MSCs secretome might provide new insights into their nature in the neural recovery. However, proteomic analysis for clinical biomarkers of OM-MSCs needs to be further studied.

  11. Cytoskeletal Reorganization Drives Mesenchymal Condensation and Regulates Downstream Molecular Signaling.

    Science.gov (United States)

    Ray, Poulomi; Chapman, Susan C

    2015-01-01

    Skeletal condensation occurs when specified mesenchyme cells self-organize over several days to form a distinctive cartilage template. Here, we determine how and when specified mesenchyme cells integrate mechanical and molecular information from their environment, forming cartilage condensations in the pharyngeal arches of chick embryos. By disrupting cytoskeletal reorganization, we demonstrate that dynamic cell shape changes drive condensation and modulate the response of the condensing cells to Fibroblast Growth Factor (FGF), Bone Morphogenetic Protein (BMP) and Transforming Growth Factor beta (TGF-β) signaling pathways. Rho Kinase (ROCK)-driven actomyosin contractions and Myosin II-generated differential cell cortex tension regulate these cell shape changes. Disruption of the condensation process inhibits the differentiation of the mesenchyme cells into chondrocytes, demonstrating that condensation regulates the fate of the mesenchyme cells. We also find that dorsal and ventral condensations undergo distinct cell shape changes. BMP signaling is instructive for dorsal condensation-specific cell shape changes. Moreover, condensations exhibit ventral characteristics in the absence of BMP signaling, suggesting that in the pharyngeal arches ventral morphology is the ground pattern. Overall, this study characterizes the interplay between cytoskeletal dynamics and molecular signaling in a self-organizing system during tissue morphogenesis.

  12. The role of bone marrow derived mesenchymal stem cells in ...

    African Journals Online (AJOL)

    The role of bone marrow derived mesenchymal stem cells in induced stroke. ... MSCs showed positive response for CD105+ (the specific marker for MSCs detection) and negative response for surface marker (CD34¯), characteristic for the hematopoietic cells. The immunohistochemistry study of intravenous administration ...

  13. Mesenchymal stem cells (MSCs) as skeletal therapeutics-an update

    DEFF Research Database (Denmark)

    Saeed, H.; Ahsan, M.; Saleem, Z.

    2016-01-01

    Mesenchymal stem cells hold the promise to treat not only several congenital and acquired bone degenerative diseases but also to repair and regenerate morbid bone tissues. Utilizing MSCs, several lines of evidences advocate promising clinical outcomes in skeletal diseases and skeletal tissue repa...

  14. Transition of mesenchymal stem/stromal cells to endothelial cells

    NARCIS (Netherlands)

    M. Crisan (Mihaela)

    2013-01-01

    textabstractMesenchymal stem/stromal cells (MSCs) are heterogeneous. A fraction of these cells constitute multipotent cells that can self-renew and mainly give rise to mesodermal lineage cells such as adipocytes, osteocytes and chondrocytes. The ability of MSCs to differentiate into endothelial

  15. Mesenchymal stem cells promote incision wound repair in a mouse ...

    African Journals Online (AJOL)

    250 cells/cm2. Conclusion: The results suggest that MSC therapies enhance the tissue regeneration capacity in mice, especially in older populations, through effective transdifferentiation into the epithelium. Keywords: Mesenchymal stem cell, wound healing, mouse. Tropical Journal of Pharmaceutical Research is indexed ...

  16. In vitro differentiation of human umbilical cord blood mesenchymal ...

    African Journals Online (AJOL)

    May H. Hasan

    2016-08-05

    Aug 5, 2016 ... Abstract Mesenchymal stem cells (MSCs) were isolated by gradient density centrifugation from umbilical cord blood. Spindle-shaped adherent cells were permitted to grow to 70% confluence in primary culture media which was reached by day 12. Induction of differentiation started by cul- turing cells with ...

  17. Amniotic fluid-derived mesenchymal stem cells as a novel ...

    African Journals Online (AJOL)

    CLEMENTINA

    2012-06-28

    Jun 28, 2012 ... As a potential alternative treatment for terminal liver diseases, amniotic fluid derived mesenchymal stem cells (AFMSCs) have many advantages over other stem cells: avoiding much ethical controversy and decrease in both quantity and differentiation potential with age. However, the therapeutic role of.

  18. Endogenous collagen influences differentiation of human multipotent mesenchymal stromal cells

    NARCIS (Netherlands)

    Fernandes, H.; Mentink, A.; Bank, R.; Stoop, R.; Blitterswijk, C. van; Boer, J. de

    2010-01-01

    Human multipotent mesenchymal stromal cells (hMSCs) are multipotent cells that, in the presence of appropriate stimuli, can differentiate into different lineages such as the osteogenic, chondrogenic, and adipogenic lineages. In the presence of ascorbic acid, MSCs secrete an extracellular matrix

  19. Endogenous Collagen Influences Differentiation of Human Multipotent Mesenchymal Stromal Cells

    NARCIS (Netherlands)

    Fernandes, H.A.M.; Mentink-Leusink, Anouk; Bank, Ruud; Stoop, Reinout; van Blitterswijk, Clemens; de Boer, Jan

    2010-01-01

    Human multipotent mesenchymal stromal cells (hMSCs) are multipotent cells that, in the presence of appropriate stimuli, can differentiate into different lineages such as the osteogenic, chondrogenic, and adipogenic lineages. In the presence of ascorbic acid, MSCs secrete an extracellular matrix

  20. Endogenous Collagen Influences Differentiation of Human Multipotent Mesenchymal Stromal Cells

    NARCIS (Netherlands)

    Fernandes, Hugo; Mentink, Anouk; Bank, Ruud; Stoop, Reinout; van Blitterswijk, Clemens; de Boer, Jan

    Human multipotent mesenchymal stromal cells (hMSCs) are multipotent cells that, in the presence of appropriate stimuli, can differentiate into different lineages such as the osteogenic, chondrogenic, and adipogenic lineages. In the presence of ascorbic acid, MSCs secrete an extracellular matrix

  1. Human mesenchymal stromal cells : biological characterization and clinical application

    NARCIS (Netherlands)

    Bernardo, Maria Ester

    2010-01-01

    This thesis focuses on the characterization of the biological and functional properties of human mesenchymal stromal cells (MSCs), isolated from different tissue sources. The differentiation capacity of MSCs from fetal and adult tissues has been tested and compared. Umbilical cord blood (UCB) has

  2. Mesenchymal stem cells promote incision wound repair in a mouse ...

    African Journals Online (AJOL)

    ... a dosage of 5 × 104 activated MSCs/8 cm2 of wound area or 6, 250 cells/cm2. Conclusion: The results suggest that MSC therapies enhance the tissue regeneration capacity in mice, especially in older populations, through effective transdifferentiation into the epithelium. Keywords: Mesenchymal stem cell, wound healing, ...

  3. Mesenchymal stem cells: cell biology and potential use in therapy

    DEFF Research Database (Denmark)

    Kassem, Moustapha; Kristiansen, Malthe; Abdallah, Basem M

    2004-01-01

    Mesenchymal stem cells are clonogenic, non-haematopoietic stem cells present in the bone marrow and are able to differentiate into multiple mesoderm-type cell lineages e.g. osteoblasts, chondrocytes, endothelial-cells and also non-mesoderm-type lineages e.g. neuronal-like cells. Several methods a...

  4. Growth and metabolism of mesenchymal stem cells cultivated on microcarriers

    NARCIS (Netherlands)

    Schop, Deborah

    2010-01-01

    Mesenchymal stem cells, MSCs, are a great potential source for clinical applications in the field of tissue regeneration. Although MSCs can be isolated from several tissues of the human body, e.g. the bone marrow, the tissues does not contain clinically relevant amounts of MSCs for cell therapeutic

  5. Research on human placenta-derived mesenchymal stem cells ...

    African Journals Online (AJOL)

    PCR) technology, amplified hVEGF165 gene fragments from human leukemia cells HL-60. hVEGF165 gene was reconstructed in pIRES2-EGFP and transferred into the human placenta-derived mesenchymal stem cells (HPMSCs) by ...

  6. Cytoskeletal Reorganization Drives Mesenchymal Condensation and Regulates Downstream Molecular Signaling.

    Directory of Open Access Journals (Sweden)

    Poulomi Ray

    Full Text Available Skeletal condensation occurs when specified mesenchyme cells self-organize over several days to form a distinctive cartilage template. Here, we determine how and when specified mesenchyme cells integrate mechanical and molecular information from their environment, forming cartilage condensations in the pharyngeal arches of chick embryos. By disrupting cytoskeletal reorganization, we demonstrate that dynamic cell shape changes drive condensation and modulate the response of the condensing cells to Fibroblast Growth Factor (FGF, Bone Morphogenetic Protein (BMP and Transforming Growth Factor beta (TGF-β signaling pathways. Rho Kinase (ROCK-driven actomyosin contractions and Myosin II-generated differential cell cortex tension regulate these cell shape changes. Disruption of the condensation process inhibits the differentiation of the mesenchyme cells into chondrocytes, demonstrating that condensation regulates the fate of the mesenchyme cells. We also find that dorsal and ventral condensations undergo distinct cell shape changes. BMP signaling is instructive for dorsal condensation-specific cell shape changes. Moreover, condensations exhibit ventral characteristics in the absence of BMP signaling, suggesting that in the pharyngeal arches ventral morphology is the ground pattern. Overall, this study characterizes the interplay between cytoskeletal dynamics and molecular signaling in a self-organizing system during tissue morphogenesis.

  7. Trophic Effects of Mesenchymal Stem Cells in Tissue Regeneration

    NARCIS (Netherlands)

    Fu, Yao; Karbaat, Lisanne; Wu, Ling; Leijten, Jeroen; Both, Sanne K.; Karperien, Marcel

    2017-01-01

    Mesenchymal stem cells (MSCs) are considered to hold great therapeutic value for cell-based therapy and for tissue regeneration in particular. Recent evidence indicates that the main underlying mechanism for MSCs' beneficial effects in tissue regeneration is based on their capability to produce a

  8. Mesenchymal Chondrosarcoma of Posterior Maxilla: Report of a ...

    African Journals Online (AJOL)

    Mesenchymal chondrosarcomas (MCs) are infrequent, slow‑growing malignant tumors of head and neck region affecting both bone and soft tissues. It represents approximately 1% of all chondrosarcomas. They usually occur in the middle aged individuals, but rarely seen in young patients. It is commonly found in the ribs ...

  9. Wnt signaling inhibits osteogenic differentiation of human mesenchymal stem cells

    NARCIS (Netherlands)

    de Boer, Jan; Siddappa, R.; Gaspar, Claudia; van Apeldoorn, Aart A.; Fodde, Riccardo; van Blitterswijk, Clemens

    2004-01-01

    Human mesenchymal stem cells (hMSCs) from the bone marrow represent a potential source of pluripotent cells for autologous bone tissue engineering. We previously discovered that over activation of the Wnt signal transduction pathway by either lithium or Wnt3A stimulates hMSC proliferation while

  10. Mesenchymal stem cell therapy in proteoglycan induced arthritis

    NARCIS (Netherlands)

    Swart, J. F.; de Roock, S.; Hofhuis, F. M.; Rozemuller, H.; van den Broek, T.; Moerer, P.; Broere, F.|info:eu-repo/dai/nl/264075323; van Wijk, F.; Kuis, W.; Prakken, B. J.; Martens, a.c.m|info:eu-repo/dai/nl/375286063; Wulffraat, N. M.

    2015-01-01

    Objectives: To explore the immunosuppressive effect and mechanism of action of intraperitoneal (ip) and intra-articular (ia) mesenchymal stem cell (MSC) injection in proteoglycan induced arthritis (PGIA). Methods: MSC were administered ip or ia after establishment of arthritis. We used serial

  11. Mesenchymal Stem Cells as Immunomodulators in a Vascularized Composite Allotransplantation

    OpenAIRE

    Yur-Ren Kuo; Chien-Chang Chen; Shigeru Goto; Pao-Yuan Lin; Fu-Chan Wei; Chao-Long Chen

    2012-01-01

    Vascularized composite allotransplantations (VCAs) are not routinely performed for tissue reconstruction because of the potentially harmful adverse effects associated with lifelong administration of immunosuppressive agents. Researchers have been eagerly seeking alternative methods that circumvent the long-term use of immunosuppressants. Mesenchymal stem cells (MSCs) show promise as an immunomodulatory therapeutic agent and are currently being tested in preclinical and clinical settings as th...

  12. Bone marrow mesenchymal stem cells: historical overview and concepts.

    Science.gov (United States)

    Charbord, Pierre

    2010-09-01

    This review describes the historical emergence of the concept of bone marrow mesenchymal stem cells (MSCs), summarizing data on Wolf and Trentin's hematopoietic inductive microenvironment; Dexter's hematopoiesis-supportive stromal cells; Friedenstein's osteogenic cells; and Pittenger's trilineal osteoblastic, chondrocytic, and adipocytic precursors; to finally introduce the specific bone marrow mesenchymal stem cells with differentiation potential to four lineages (mesenchymal and vascular smooth muscle lineages), and stromal and immunomodulatory capacities. Two points are the object of detailed discussion. The first point envisions the stem cell attributes (multipotentiality, self-renewal, tissue regeneration, population heterogeneity, plasticity, and lineage priming) compared with that of the paradigmatic hematopoietic stem cell. In the second point, we discuss the possible existence of bone marrow cells with greater differentiation potential, eventually pluripotential cells. The latter point raises the issues of cell fusion, reprogramming, or selection under nonstandardized conditions of rare populations of neuroectodermal origin, or of cells that had undergone mesenchymal-to-epithelial transition. In the last section, we review data on MSC senescence and possible malignant transformation secondary to extensive culture, gene transfer of telomerase, or mutations such as leading to Ewing's sarcoma. The set of data leads to the conclusion that bone marrow MSCs constitute a specific adult tissue stem cell population. The multiple characteristics of this stem cell type account for the versatility of the mechanisms of injured tissue repair. Although MSC administration may be extremely useful in a number of clinical applications, their transplantation is not without risks that must not be overlooked when developing cell therapy protocols.

  13. In vitro differentiation of human umbilical cord blood mesenchymal ...

    African Journals Online (AJOL)

    Mesenchymal stem cells (MSCs) were isolated by gradient density centrifugation from umbilical cord blood. Spindle-shaped adherent cells were permitted to grow to 70% confluence in primary culture media which was reached by day 12. Induction of differentiation started by culturing cells with differentiation medium ...

  14. Human bone-marrow-derived mesenchymal stem cells

    DEFF Research Database (Denmark)

    Kassem, Moustapha; Abdallah, Basem M

    2008-01-01

    Mesenchymal stem cells (MSC) are a group of cells present in bone-marrow stroma and the stroma of various organs with the capacity for mesoderm-like cell differentiation into, for example, osteoblasts, adipocytes, and chondrocytes. MSC are being introduced in the clinic for the treatment...

  15. Human bone marrow-derived mesenchymal stem cells | Nasef ...

    African Journals Online (AJOL)

    Mesenchymal stem cells (MSCs) have elicited a great clinical interest, particularly in the areas of regenerative medicine and induction of tolerance in allogeneic transplantation. Previous reports demonstrated the feasibility of transplanting MSCs, which generates new prospects in cellular therapy. Recently, injection of ...

  16. Mesenchymal Stem Cell-Based Therapy for Prostate Cancer

    Science.gov (United States)

    2014-09-01

    graft versus host disease, inflammatory bowel disease and myocardial infarction in clinical trials. These clinical studies have documented that... myocardial infarction in clinical trials. Conclusions These results document two things. First, the therapeutic agent loaded into hbMSCs must...Mesenchymal Stem Cell-Based Therapy for Prostate Cancer PRINCIPAL INVESTIGATOR: John Isaacs; Jeffrey Karp

  17. MRI appearance of mesenchymal tumors of the uterus

    Energy Technology Data Exchange (ETDEWEB)

    Cornfeld, Daniel [Department of Diagnostic Radiology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510 (United States)], E-mail: daniel.cornfeld@yale.edu; Israel, Gary [Department of Diagnostic Radiology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510 (United States); Martel, Maritza [Department of Pathology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510 (United States); Weinreb, Jeffery [Department of Diagnostic Radiology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510 (United States); Schwartz, Peter [Department of Obstetrics and Gynecology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510 (United States); McCarthy, Shirley [Department of Diagnostic Radiology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510 (United States)

    2010-04-15

    Purpose: Uterine leiomyomas are the most common uterine neoplasms. Statistically, a uterine mass with unusual imaging features is more likely to represent a leiomyoma than other uncommon uterine mesenchymal neoplasms such as leiomyosarcoma or endometrial stromal tumors. Several prior studies have attempted to identify objective imaging characteristics that differentiate these entities. The purpose of this study was to test these criteria on our patient population. Methods and materials: This retrospective study was approved by the institutional Human Investigations Committee and was performed in compliance with HIPAA regulations. Four patients with uterine leiomyosarcoma, two with stromal tumors of uncertain malignant potential (STUMP), one with endometrial stromal sarcoma, and two with mixed endometrial stromal and smooth muscle tumors were included in the study. Seventeen additional control cases of leiomyomas were selected as controls. Cases were blindly evaluated by two experienced readers. Objective criteria included T1 and T2 signal characteristics, enhancement pattern, the presence of cystic changes, and ill defined margins. Subjective criteria included individual reader gestalt. All cases had pathologic correlation. Results: None of the objective criteria were associated with the presence or absence of uterine mesenchymal neoplasm. Ill defined margins came closest to having statistical significance (p = 0.06). Reader gestalt was statistically associated with the presence of mesenchymal neoplasm for one of our readers (p = 0.02) but not for the other (p = 0.07). Conclusion: We found poor accuracy for objective imaging criteria in distinguishing leiomyomas with atypical imaging features from more clinically significant uterine mesenchymal neoplasms.

  18. Hypophosphataemia-inducing mesenchymal tumour in the foot.

    Science.gov (United States)

    Bauer, Christa; Brücker, Rolf; Bützberger, Stefan; Schmid, Christoph

    2010-10-06

    Tumour-induced (or oncogenic) osteomalacia is a paraneoplastic syndrome characterised by progressive fatigue, muscle weakness, bone pain, non-healing and recurrent fractures caused by mesenchymal tumours that secrete proteins that inhibit renal phosphate transport and 1α-hydroxylation of 25-OH-vitamin D. The potentially curative treatment of choice is complete surgical excision of the tumour.

  19. Mesenchymal chondrosarcoma of the spleen: report of a case.

    Science.gov (United States)

    Rossetto, Anna; Saccomano, Enrico; Zompicchiatti, Aron; Avellini, Claudio; Toffoli, Silvia; Miolo, GianMaria; Frustaci, Sergio; Uzzau, Alessandro

    2011-01-01

    Chondrosarcoma is a malignant tumor of chondrogenic origin and the mesenchymal type is a very rare finding. Mesenchymal chondrosarcoma tends to develop mostly in the skeleton but may also occur as a primary tumor in periosteal nervous and muscular tissues, the anterior cerebral falx, meninges, brain, maxillary sinus, eyelid, thyroid, pleura and mediastinum, while in the abdomen the most frequent locations are the kidney, retroperitoneum and even the perineum and the anogenital area. Apparently, the only splenic mesenchymal chondrosarcoma in the literature occurred in a dog. Our paper reports the case of a patient who had a diagnosis of mesenchymal chondrosarcoma of the spleen. Results. We adopted surgery as the main therapeutic procedure without achieving complete recovery but preserving a good quality of life for our patient, minimizing the repercussions of the disease on her working and relational life. The absence of important or invalidating symptoms and the persistence of good general conditions before and after each surgical operation encouraged us to adopt the surgical option as the most rational.

  20. Neural networks for triggering

    Energy Technology Data Exchange (ETDEWEB)

    Denby, B. (Fermi National Accelerator Lab., Batavia, IL (USA)); Campbell, M. (Michigan Univ., Ann Arbor, MI (USA)); Bedeschi, F. (Istituto Nazionale di Fisica Nucleare, Pisa (Italy)); Chriss, N.; Bowers, C. (Chicago Univ., IL (USA)); Nesti, F. (Scuola Normale Superiore, Pisa (Italy))

    1990-01-01

    Two types of neural network beauty trigger architectures, based on identification of electrons in jets and recognition of secondary vertices, have been simulated in the environment of the Fermilab CDF experiment. The efficiencies for B's and rejection of background obtained are encouraging. If hardware tests are successful, the electron identification architecture will be tested in the 1991 run of CDF. 10 refs., 5 figs., 1 tab.

  1. Artificial neural network modelling

    CERN Document Server

    Samarasinghe, Sandhya

    2016-01-01

    This book covers theoretical aspects as well as recent innovative applications of Artificial Neural networks (ANNs) in natural, environmental, biological, social, industrial and automated systems. It presents recent results of ANNs in modelling small, large and complex systems under three categories, namely, 1) Networks, Structure Optimisation, Robustness and Stochasticity 2) Advances in Modelling Biological and Environmental Systems and 3) Advances in Modelling Social and Economic Systems. The book aims at serving undergraduates, postgraduates and researchers in ANN computational modelling. .

  2. Neurally-mediated sincope.

    Science.gov (United States)

    Can, I; Cytron, J; Jhanjee, R; Nguyen, J; Benditt, D G

    2009-08-01

    Syncope is a syndrome characterized by a relatively sudden, temporary and self-terminating loss of consciousness; the causes may vary, but they have in common a temporary inadequacy of cerebral nutrient flow, usually due to a fall in systemic arterial pressure. However, while syncope is a common problem, it is only one explanation for episodic transient loss of consciousness (TLOC). Consequently, diagnostic evaluation should start with a broad consideration of real or seemingly real TLOC. Among those patients in whom TLOC is deemed to be due to ''true syncope'', the focus may then reasonably turn to assessing the various possible causes; in this regard, the neurally-mediated syncope syndromes are among the most frequently encountered. There are three common variations: vasovagal syncope (often termed the ''common'' faint), carotid sinus syndrome, and the so-called ''situational faints''. Defining whether the cause is due to a neurally-mediated reflex relies heavily on careful history taking and selected testing (e.g., tilt-test, carotid massage). These steps are important. Despite the fact that neurally-mediated faints are usually relatively benign from a mortality perspective, they are nevertheless only infrequently an isolated event; neurally-mediated syncope tends to recur, and physical injury resulting from falls or accidents, diminished quality-of-life, and possible restriction from employment or avocation are real concerns. Consequently, defining the specific form and developing an effective treatment strategy are crucial. In every case the goal should be to determine the cause of syncope with sufficient confidence to provide patients and family members with a reliable assessment of prognosis, recurrence risk, and treatment options.

  3. The Neural Noisy Channel

    OpenAIRE

    Yu, Lei; Blunsom, Phil; Dyer, Chris; Grefenstette, Edward; Kocisky, Tomas

    2016-01-01

    We formulate sequence to sequence transduction as a noisy channel decoding problem and use recurrent neural networks to parameterise the source and channel models. Unlike direct models which can suffer from explaining-away effects during training, noisy channel models must produce outputs that explain their inputs, and their component models can be trained with not only paired training samples but also unpaired samples from the marginal output distribution. Using a latent variable to control ...

  4. How Tissue Mechanical Properties Affect Enteric Neural Crest Cell Migration

    Science.gov (United States)

    Chevalier, N. R.; Gazguez, E.; Bidault, L.; Guilbert, T.; Vias, C.; Vian, E.; Watanabe, Y.; Muller, L.; Germain, S.; Bondurand, N.; Dufour, S.; Fleury, V.

    2016-02-01

    Neural crest cells (NCCs) are a population of multipotent cells that migrate extensively during vertebrate development. Alterations to neural crest ontogenesis cause several diseases, including cancers and congenital defects, such as Hirschprung disease, which results from incomplete colonization of the colon by enteric NCCs (ENCCs). We investigated the influence of the stiffness and structure of the environment on ENCC migration in vitro and during colonization of the gastrointestinal tract in chicken and mouse embryos. We showed using tensile stretching and atomic force microscopy (AFM) that the mesenchyme of the gut was initially soft but gradually stiffened during the period of ENCC colonization. Second-harmonic generation (SHG) microscopy revealed that this stiffening was associated with a gradual organization and enrichment of collagen fibers in the developing gut. Ex-vivo 2D cell migration assays showed that ENCCs migrated on substrates with very low levels of stiffness. In 3D collagen gels, the speed of the ENCC migratory front decreased with increasing gel stiffness, whereas no correlation was found between porosity and ENCC migration behavior. Metalloprotease inhibition experiments showed that ENCCs actively degraded collagen in order to progress. These results shed light on the role of the mechanical properties of tissues in ENCC migration during development.

  5. Neural crest specification by noncanonical Wnt signaling and PAR-1

    Science.gov (United States)

    Ossipova, Olga; Sokol, Sergei Y.

    2011-01-01

    Neural crest (NC) cells are multipotent progenitors that form at the neural plate border, undergo epithelial-mesenchymal transition and migrate to diverse locations in vertebrate embryos to give rise to many cell types. Multiple signaling factors, including Wnt proteins, operate during early embryonic development to induce the NC cell fate. Whereas the requirement for the Wnt/β-catenin pathway in NC specification has been well established, a similar role for Wnt proteins that do not stabilize β-catenin has remained unclear. Our gain- and loss-of-function experiments implicate Wnt11-like proteins in NC specification in Xenopus embryos. In support of this conclusion, modulation of β-catenin-independent signaling through Dishevelled and Ror2 causes predictable changes in premigratory NC. Morpholino-mediated depletion experiments suggest that Wnt11R, a Wnt protein that is expressed in neuroectoderm adjacent to the NC territory, is required for NC formation. Wnt11-like signals might specify NC by altering the localization and activity of the serine/threonine polarity kinase PAR-1 (also known as microtubule-associated regulatory kinase or MARK), which itself plays an essential role in NC formation. Consistent with this model, PAR-1 RNA rescues NC markers in embryos in which noncanonical Wnt signaling has been blocked. These experiments identify novel roles for Wnt11R and PAR-1 in NC specification and reveal an unexpected connection between morphogenesis and cell fate. PMID:22110058

  6. Neural Based Orthogonal Data Fitting The EXIN Neural Networks

    CERN Document Server

    Cirrincione, Giansalvo

    2008-01-01

    Written by three leaders in the field of neural based algorithms, Neural Based Orthogonal Data Fitting proposes several neural networks, all endowed with a complete theory which not only explains their behavior, but also compares them with the existing neural and traditional algorithms. The algorithms are studied from different points of view, including: as a differential geometry problem, as a dynamic problem, as a stochastic problem, and as a numerical problem. All algorithms have also been analyzed on real time problems (large dimensional data matrices) and have shown accurate solutions. Wh

  7. Neural crest cells pattern the surface cephalic ectoderm during FEZ formation.

    Science.gov (United States)

    Hu, Diane; Marcucio, Ralph S

    2012-04-01

    Multiple fibroblast growth factor (Fgf) ligands are expressed in the forebrain and facial ectoderm, and vascular endothelial growth factor (VEGF) is expressed in the facial ectoderm. Both pathways activate the MAP kinase cascade and can be suppressed by SU5402. We placed a bead soaked in SU5402 into the brain after emigration of neural crest cells was complete. Within 24 hr we observed reduced pMEK and pERK staining that persisted for at least 48 hr. This was accompanied by significant apoptosis in the face. By day 15, the upper beaks were truncated. Molecular changes in the FNP were also apparent. Normally, Shh is expressed in the frontonasal ectodermal zone and controls patterned growth of the upper jaw. In treated embryos, Shh expression was reduced. Both the structural and molecular deficits were mitigated after transplantation of FNP-derived mesenchymal cells. Thus, mesenchymal cells actively participate in signaling interactions of the face, and the absence of neural crest cells in neurocristopathies may not be merely structural. Copyright © 2012 Wiley Periodicals, Inc.

  8. Neural crest cells pattern the surface cephalic ectoderm during FEZ formation

    Science.gov (United States)

    Hu, Diane; Marcucio, Ralph S.

    2012-01-01

    Multiple Fibroblast growth factor (Fgf) ligands are expressed in the forebrain and facial ectoderm, and Vascular Endothelial Growth Factor (VEGF) is expressed in the facial ectoderm. Both pathways activate the MAP kinase cascade and can be suppressed by SU5402. We placed a bead soaked in SU5402 into the brain after emigration of neural crest cells was complete. Within 24 hours we observed reduced pMEK and pERK staining that persisted for at least 48 hours. This was accompanied by significant apoptosis in the face. By day 15 the upper beaks were truncated. Molecular changes in the FNP were also apparent. Normally, Shh is expressed in the Frontonasal Ectodermal Zone and controls patterned growth of the upper jaw. In treated embryos Shh expression was reduced. Both the structural and molecular deficits were mitigated after transplantation of FNP-derived mesenchymal cells. Thus, mesenchymal cells actively participate in signaling interactions of the face, and the absence of neural crest cells in neurocristopathies may not be merely structural. PMID:22411554

  9. Long noncoding RNAs related to the odontogenic potential of dental mesenchymal cells in mice.

    Science.gov (United States)

    Zheng, Yunfei; Jia, Lingfei

    2016-07-01

    The purpose of this study is to identify the lncRNAs that are associated with the odontogenic potential in mouse dental mesenchymal cells. The odontogenic potential of dental mesenchymal cells was found to be lost in the course of in vitro culture, so the lncRNA profiles were subsequently compared between freshly-isolated and cultured dental mesenchymal cells using RNA-sequencing. A co-expression analysis of differentially expressed lncRNAs and coding RNAs was performed to understand their potential functions. The expression of several selected lncRNAs was also examined in developing tooth germs. Compared with cultured dental mesenchymal cells, 108 lncRNAs were upregulated and 36 lncRNAs were downregulated in freshly-isolated dental mesenchymal cells. Coding genes correlated with the lncRNAs were mainly associated with DNA and protein metabolic processes and cytoskeletal anchorage. Meg3, Malat1, Xist, and Dlx1as were significantly downregulated in cultured dental mesenchymal cells but were upregulated in odontogenic dental mesenchymal tissues. Moreover, the levels of Dlx1as were negatively correlated with that of Dlx1 in dental mesenchymal cells and dental mesenchymal tissues. The lncRNA profiles of dental mesenchymal cells are significantly changed during culturing, and the dysregulation of lncRNAs is associated with the loss of odontogenic potential. Copyright © 2016. Published by Elsevier Ltd.

  10. Neural Correlates of Stimulus Reportability

    OpenAIRE

    Hulme, Oliver J.; Friston, Karl F.; Zeki, Semir

    2009-01-01

    Most experiments on the “neural correlates of consciousness” employ stimulus reportability as an operational definition of what is consciously perceived. The interpretation of such experiments therefore depends critically on understanding the neural basis of stimulus reportability. Using a high volume of fMRI data, we investigated the neural correlates of stimulus reportability using a partial report object detection paradigm. Subjects were presented with a random array of circularly arranged...

  11. Symbolic processing in neural networks

    OpenAIRE

    Neto, João Pedro; Hava T Siegelmann; Costa,J.Félix

    2003-01-01

    In this paper we show that programming languages can be translated into recurrent (analog, rational weighted) neural nets. Implementation of programming languages in neural nets turns to be not only theoretical exciting, but has also some practical implications in the recent efforts to merge symbolic and sub symbolic computation. To be of some use, it should be carried in a context of bounded resources. Herein, we show how to use resource bounds to speed up computations over neural nets, thro...

  12. Human mesenchymal cells from adipose tissue deposit laminin and promote regeneration of injured spinal cord in rats.

    Science.gov (United States)

    Menezes, Karla; Nascimento, Marcos Assis; Gonçalves, Juliana Pena; Cruz, Aline Silva; Lopes, Daiana Vieira; Curzio, Bianca; Bonamino, Martin; de Menezes, João Ricardo Lacerda; Borojevic, Radovan; Rossi, Maria Isabel Doria; Coelho-Sampaio, Tatiana

    2014-01-01

    Cell therapy is a promising strategy to pursue the unmet need for treatment of spinal cord injury (SCI). Although several studies have shown that adult mesenchymal cells contribute to improve the outcomes of SCI, a description of the pro-regenerative events triggered by these cells is still lacking. Here we investigated the regenerative properties of human adipose tissue derived stromal cells (hADSCs) in a rat model of spinal cord compression. Cells were delivered directly into the spinal parenchyma immediately after injury. Human ADSCs promoted functional recovery, tissue preservation, and axonal regeneration. Analysis of the cord tissue showed an abundant deposition of laminin of human origin at the lesion site and spinal midline; the appearance of cell clusters composed of neural precursors in the areas of laminin deposition, and the appearance of blood vessels with separated basement membranes along the spinal axis. These effects were also observed after injection of hADSCs into non-injured spinal cord. Considering that laminin is a well-known inducer of axonal growth, as well a component of the extracellular matrix associated to neural progenitors, we propose that it can be the paracrine factor mediating the pro-regenerative effects of hADSCs in spinal cord injury.

  13. Extracellular matrix from human umbilical cord-derived mesenchymal stem cells as a scaffold for peripheral nerve regeneration.

    Science.gov (United States)

    Xiao, Bo; Rao, Feng; Guo, Zhi-Yuan; Sun, Xun; Wang, Yi-Guo; Liu, Shu-Yun; Wang, Ai-Yuan; Guo, Quan-Yi; Meng, Hao-Ye; Zhao, Qing; Peng, Jiang; Wang, Yu; Lu, Shi-Bi

    2016-07-01

    The extracellular matrix, which includes collagens, laminin, or fibronectin, plays an important role in peripheral nerve regeneration. Recently, a Schwann cell-derived extracellular matrix with classical biomaterial was used to mimic the neural niche. However, extensive clinical use of Schwann cells remains limited because of the limited origin, loss of an autologous nerve, and extended in vitro culture times. In the present study, human umbilical cord-derived mesenchymal stem cells (hUCMSCs), which are easily accessible and more proliferative than Schwann cells, were used to prepare an extracellular matrix. We identified the morphology and function of hUCMSCs and investigated their effect on peripheral nerve regeneration. Compared with a non-coated dish tissue culture, the hUCMSC-derived extracellular matrix enhanced Schwann cell proliferation, upregulated gene and protein expression levels of brain-derived neurotrophic factor, glial cell-derived neurotrophic factor, and vascular endothelial growth factor in Schwann cells, and enhanced neurite outgrowth from dorsal root ganglion neurons. These findings suggest that the hUCMSC-derived extracellular matrix promotes peripheral nerve repair and can be used as a basis for the rational design of engineered neural niches.

  14. [Artificial neural networks in Neurosciences].

    Science.gov (United States)

    Porras Chavarino, Carmen; Salinas Martínez de Lecea, José María

    2011-11-01

    This article shows that artificial neural networks are used for confirming the relationships between physiological and cognitive changes. Specifically, we explore the influence of a decrease of neurotransmitters on the behaviour of old people in recognition tasks. This artificial neural network recognizes learned patterns. When we change the threshold of activation in some units, the artificial neural network simulates the experimental results of old people in recognition tasks. However, the main contributions of this paper are the design of an artificial neural network and its operation inspired by the nervous system and the way the inputs are coded and the process of orthogonalization of patterns.

  15. Neural Correlates of Face Detection

    National Research Council Canada - National Science Library

    Xu, Xiaokun; Biederman, Irving

    2014-01-01

    Although face detection likely played an essential adaptive role in our evolutionary past and in contemporary social interactions, there have been few rigorous studies investigating its neural correlates...

  16. Priming of endothelial colony-forming cells in a mesenchymal niche improves engraftment and vasculogenic potential by initiating mesenchymal transition orchestrated by NOTCH signaling.

    Science.gov (United States)

    Shafiee, Abbas; Patel, Jatin; Wong, Ho Yi; Donovan, Prudence; Hutmacher, Dietmar W; Fisk, Nicholas M; Khosrotehrani, Kiarash

    2017-02-01

    The prospect of using endothelial progenitors is currently hampered by their low engraftment upon transplantation. We report that mesenchymal stem/stromal cells (MSCs), independent of source and age, improve the engraftment of endothelial colony forming cells (ECFCs). MSC coculture altered ECFC appearance to an elongated mesenchymal morphology with reduced proliferation. ECFC primed via MSC contact had reduced self-renewal potential, but improved capacity to form tube structures in vitro and engraftment in vivo Primed ECFCs displayed major differences in transcriptome compared to ECFCs never exposed to MSCs, affecting genes involved in the cell cycle, up-regulating of genes influencing mesenchymal transition, adhesion, extracellular matrix. Inhibition of NOTCH signaling, a potential upstream regulator of mesenchymal transition, in large part modulated this gene expression pattern and functionally reversed the mesenchymal morphology of ECFCs. The collective results showed that primed ECFCs survive better and undergo a mesenchymal transition that is dependent on NOTCH signaling, resulting in significantly increased vasculogenic potential.-Shafiee, A., Patel, J., Wong, H. Y., Donovan, P., Hutmacher, D. W., Fisk, N. M., Khosrotehrani, K. Priming of endothelial colony-forming cells in a mesenchymal niche improves engraftment and vasculogenic potential by initiating mesenchymal transition orchestrated by NOTCH signaling. © FASEB.

  17. Optics in neural computation

    Science.gov (United States)

    Levene, Michael John

    In all attempts to emulate the considerable powers of the brain, one is struck by both its immense size, parallelism, and complexity. While the fields of neural networks, artificial intelligence, and neuromorphic engineering have all attempted oversimplifications on the considerable complexity, all three can benefit from the inherent scalability and parallelism of optics. This thesis looks at specific aspects of three modes in which optics, and particularly volume holography, can play a part in neural computation. First, holography serves as the basis of highly-parallel correlators, which are the foundation of optical neural networks. The huge input capability of optical neural networks make them most useful for image processing and image recognition and tracking. These tasks benefit from the shift invariance of optical correlators. In this thesis, I analyze the capacity of correlators, and then present several techniques for controlling the amount of shift invariance. Of particular interest is the Fresnel correlator, in which the hologram is displaced from the Fourier plane. In this case, the amount of shift invariance is limited not just by the thickness of the hologram, but by the distance of the hologram from the Fourier plane. Second, volume holography can provide the huge storage capacity and high speed, parallel read-out necessary to support large artificial intelligence systems. However, previous methods for storing data in volume holograms have relied on awkward beam-steering or on as-yet non- existent cheap, wide-bandwidth, tunable laser sources. This thesis presents a new technique, shift multiplexing, which is capable of very high densities, but which has the advantage of a very simple implementation. In shift multiplexing, the reference wave consists of a focused spot a few millimeters in front of the hologram. Multiplexing is achieved by simply translating the hologram a few tens of microns or less. This thesis describes the theory for how shift

  18. Signaling pathways regulating the expression of Prx1 and Prx2 in the Chick Mandibular Mesenchyme

    Science.gov (United States)

    Doufexi, Aikaterini-El; Mina, Mina

    2009-01-01

    Prx1 and Prx2 are members of the aristaless-related homeobox genes shown to play redundant but essential roles in morphogenesis of the mandibular processes. To gain insight into the signaling pathways that regulate expression of Prx genes in the mandibular mesenchyme, we used the chick as a model system. We examined the patterns of gene expression in the face and the roles of signals derived from the epithelium on the expression of Prx genes in the mandibular mesenchyme. Our results demonstrated stage-dependent roles of mandibular epithelium on the expression of Prx in the mandibular mesenchyme and provide evidence for positive roles of members of the fibroblast and hedgehog families derived from mandibular epithelium on the expression of Prx genes in the mandibular mesenchyme. Our studies suggest that endothelin-1 signaling derived from the mesenchyme is involved in restricting the expression of Prx2 to the medial mandibular mesenchyme. PMID:18942149

  19. Analysis of neural networks

    CERN Document Server

    Heiden, Uwe

    1980-01-01

    The purpose of this work is a unified and general treatment of activity in neural networks from a mathematical pOint of view. Possible applications of the theory presented are indica­ ted throughout the text. However, they are not explored in de­ tail for two reasons : first, the universal character of n- ral activity in nearly all animals requires some type of a general approach~ secondly, the mathematical perspicuity would suffer if too many experimental details and empirical peculiarities were interspersed among the mathematical investigation. A guide to many applications is supplied by the references concerning a variety of specific issues. Of course the theory does not aim at covering all individual problems. Moreover there are other approaches to neural network theory (see e.g. Poggio-Torre, 1978) based on the different lev­ els at which the nervous system may be viewed. The theory is a deterministic one reflecting the average be­ havior of neurons or neuron pools. In this respect the essay is writt...

  20. AKI Recovery Induced by Mesenchymal Stromal Cell-Derived Extracellular Vesicles Carrying MicroRNAs

    OpenAIRE

    Collino, Federica; Bruno, Stefania; Incarnato, Danny; Dettori, Daniela; Neri, Francesco; Provero, Paolo; Pomatto, Margherita; Oliviero, Salvatore; Tetta, Ciro; Quesenberry, Peter J.; Camussi, Giovanni

    2015-01-01

    Phenotypic changes induced by extracellular vesicles have been implicated in mesenchymal stromal cell–promoted recovery of AKI. MicroRNAs are potential candidates for cell reprogramming toward a proregenerative phenotype. The aim of this study was to evaluate whether microRNA deregulation inhibits the regenerative potential of mesenchymal stromal cells and derived extracellular vesicles in a model of glycerol-induced AKI in severe combined immunodeficient mice. We generated mesenchymal stroma...

  1. Artificial Neural Networks·

    Indian Academy of Sciences (India)

    differences between biological neural networks (BNNs) of the brain and ANN s. A thorough understanding of ... neurons. Artificial neural models are loosely based on biology since a complete understanding of the .... A learning scheme for updating a neuron's connections (weights) was proposed by Donald Hebb in 1949.

  2. Neural Networks for Optimal Control

    DEFF Research Database (Denmark)

    Sørensen, O.

    1995-01-01

    Two neural networks are trained to act as an observer and a controller, respectively, to control a non-linear, multi-variable process.......Two neural networks are trained to act as an observer and a controller, respectively, to control a non-linear, multi-variable process....

  3. The Neural Support Vector Machine

    NARCIS (Netherlands)

    Wiering, Marco; van der Ree, Michiel; Embrechts, Mark; Stollenga, Marijn; Meijster, Arnold; Nolte, A; Schomaker, Lambertus

    2013-01-01

    This paper describes a new machine learning algorithm for regression and dimensionality reduction tasks. The Neural Support Vector Machine (NSVM) is a hybrid learning algorithm consisting of neural networks and support vector machines (SVMs). The output of the NSVM is given by SVMs that take a

  4. Transplantation of mesenchymal stem cells exerts anti-apoptotic effects in adult rats after spinal cord ischemia-reperfusion injury.

    Science.gov (United States)

    Yin, Fei; Guo, Li; Meng, Chun-yang; Liu, Ya-juan; Lu, Ri-feng; Li, Peng; Zhou, Yu-bo

    2014-05-02

    It is unknown whether transplantation of bone marrow mesenchymal stem cells (BM-MSCs) can repair spinal cord ischemia-reperfusion injury (SCII) in a rat model through an anti-apoptotic effect. Adult rats were divided into untreated or sham-operated controls, untreated models of SCII (uSCII) and BM-MSC-transplanted models of SCII (tSCII; labeled with CM-Dill transplanted at 1 h and 24 h after reperfusion). According to evaluation of hind-limb motor function, the motor functions of tSCII rats were significantly better than those of uSCII rats by the seventh day. H&E and TUNEL staining showed that the spinal cords of uSCII rats contained damaged neural cells with nuclear pyknosis and congestion of blood vessels, with a high percentage of apoptotic neural cells, while the spinal cords of tSCII rats were nearly normal with significantly fewer apoptotic neural cells. Immunohistochemistry and double immunofluorescence staining revealed that in tSCII rats CASP3 and neurofilament-H (NF-H) levels were 14.57% and 174% those of uSCII rats, respectively, and in tSCII rats the ratio of BAX to BCL2 was reduced by nearly 50%. The differentiation of transplanted CM-Dil-labeled BM-MSCs into neurons and astrocytes was observed in the spinal cords of the tSCII rats under laser scanning confocal microscopy. These results showed that transplantation of BM-MSCs improved functional recovery after SCII via anti-apoptosis. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Mesenchymal stem cell therapies in the treatment of musculoskeletal diseases.

    Science.gov (United States)

    Bashir, Jamil; Sherman, Andrew; Lee, Henry; Kaplan, Lee; Hare, Joshua M

    2014-01-01

    The application of regenerative strategies to musculoskeletal ailments offers extraordinary promise to transform management of the conditions of numerous patients. The use of cell-based therapies and adjunct strategies is under active investigation for injuries and illnesses affecting bones, joints, tendons, and skeletal muscle. Of particular interest to the field is the mesenchymal stem cell, an adult stem cell found in bone marrow and adipose tissue. This cell type can be expanded ex vivo, has allogeneic application, and has the capacity for engraftment and differentiation into mesodermal lineages. Also of major interest in the field is the use of platelet-rich plasma, a strategy to concentrate endogenous cytokines and growth factors with reparative potential. Here we review the biological basis, clinical studies, safety, and current state of mesenchymal stem cell and platelet-rich plasma therapies in the treatment of musculoskeletal disease. Copyright © 2014 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

  6. Complex Determinants of Epithelial: Mesenchymal Phenotypic Plasticity in Ovarian Cancer

    Science.gov (United States)

    Klymenko, Yuliya; Kim, Oleg; Stack, M. Sharon

    2017-01-01

    Unlike most epithelial malignancies which metastasize hematogenously, metastasis of epithelial ovarian cancer (EOC) occurs primarily via transcoelomic dissemination, characterized by exfoliation of cells from the primary tumor, avoidance of detachment-induced cell death (anoikis), movement throughout the peritoneal cavity as individual cells and multi-cellular aggregates (MCAs), adhesion to and disruption of the mesothelial lining of the peritoneum, and submesothelial matrix anchoring and proliferation to generate widely disseminated metastases. This exceptional microenvironment is highly permissive for phenotypic plasticity, enabling mesenchymal-to-epithelial (MET) and epithelial-to-mesenchymal (EMT) transitions. In this review, we summarize current knowledge on EOC heterogeneity in an EMT context, outline major regulators of EMT in ovarian cancer, address controversies in EMT and EOC chemoresistance, and highlight computational modeling approaches toward understanding EMT/MET in EOC. PMID:28792442

  7. Epithelial-mesenchymal transition in prostate cancer: an overview

    Science.gov (United States)

    Montanari, Micaela; Rossetti, Sabrina; Cavaliere, Carla; D'Aniello, Carmine; Malzone, Maria Gabriella; Vanacore, Daniela; Franco, Rossella Di; Mantia, Elvira La; Iovane, Gelsomina; Piscitelli, Raffaele; Muscariello, Raffaele; Berretta, Massimiliano; Perdonà, Sisto; Muto, Paolo; Botti, Gerardo; Bianchi, Attilio Antonio Montano; Veneziani, Bianca Maria; Facchini, Gaetano

    2017-01-01

    Prostate cancer is a main urological disease associated with significant morbidity and mortality. Radical prostatectomy and radiotherapy are potentially curative for localized prostate cancer, while androgen deprivation therapy is the initial systemic therapy for metastatic prostate disease. However, despite temporary response, most patients relapse and evolve into castration resistant cancer. Epithelial-mesenchymal transition (EMT) is a complex gradual process that occurs during embryonic development and/or tumor progression. During this process, cells lose their epithelial characteristics and acquire mesenchymal features. Increasing evidences indicate that EMT promotes prostate cancer metastatic progression and it is closely correlated with increased stemness and drug resistance. In this review, we discuss the main molecular events that directly or indirectly govern the EMT program in prostate cancer, in order to better define the role and the mechanisms underlying this process in prostate cancer progression and therapeutic resistance. PMID:28430640

  8. Telomere stability and telomerase in mesenchymal stem cells

    DEFF Research Database (Denmark)

    Serakinci, Nedime; Graakjaer, Jesper; Kølvrå, Steen

    2008-01-01

    Telomeres are repetitive genetic material that cap and thereby protect the ends of chromosomes. Each time a cell divides, telomeres get shorter. Telomere length is mainly maintained by telomerase. This enzyme is present in high concentrations in the embryonic stem cells and in fast growing...... embryonic cells, and declines with age. It is still unclear to what extent there is telomerase in adult stem cells, but since these are the founder cells of cells of all the tissues in the body, understanding the telomere dynamics and expression of telomerase in adult stem cells is very important....... In the present communication we focus on telomere expression and telomere length in stem cells, with a special focus on mesenchymal stem cells. We consider different mechanisms by which stem cells can maintain telomeres and also focus on the dynamics of telomere length in mesenchymal stem cells, both the overall...

  9. Epithelial-mesenchymal transition: Understanding the basic concept

    Directory of Open Access Journals (Sweden)

    Suresh Babu Ghanta

    2012-01-01

    Full Text Available The epithelial-mesenchymal transition (EMT is described as a rapid and reversible process of change of cell phenotype seen during embryonic development, organ fibrosis, and tumor progression. EMT was first described by Gary Greenberg and Elizabeth Hay in 1982. During EMT the epithelial cells alter their cell polarity, reorganize their cytoskeleton thus become isolated and motile. Depending upon the biological context in which they occur, EMT is divided into three types namely EMT type I, II, III. The article describes the process of EMT implicated in the oral cavity as in palate and root development (type I EMT, gingival fibromatosis and oral sub-mucous fibrosis (type II EMT, and oral squamous cell carcinoma (type III EMT. The reverse process of EMT is called as mesenchymal-epithelial transition seen in association with kidney formation.

  10. Neural fields theory and applications

    CERN Document Server

    Graben, Peter; Potthast, Roland; Wright, James

    2014-01-01

    With this book, the editors present the first comprehensive collection in neural field studies, authored by leading scientists in the field - among them are two of the founding-fathers of neural field theory. Up to now, research results in the field have been disseminated across a number of distinct journals from mathematics, computational neuroscience, biophysics, cognitive science and others. Starting with a tutorial for novices in neural field studies, the book comprises chapters on emergent patterns, their phase transitions and evolution, on stochastic approaches, cortical development, cognition, robotics and computation, large-scale numerical simulations, the coupling of neural fields to the electroencephalogram and phase transitions in anesthesia. The intended readership are students and scientists in applied mathematics, theoretical physics, theoretical biology, and computational neuroscience. Neural field theory and its applications have a long-standing tradition in the mathematical and computational ...

  11. The Neural Correlates of Race

    Science.gov (United States)

    Ito, Tiffany A.; Bartholow, Bruce D.

    2009-01-01

    Behavioral analyses are a natural choice for understanding the wide-ranging behavioral consequences of racial stereotyping and prejudice. However, neuroimaging and electrophysiological research has recently considered the neural mechanisms that underlie racial categorization and the activation and application of racial stereotypes and prejudice, revealing exciting new insights. Work reviewed here points to the importance of neural structures previously associated with face processing, semantic knowledge activation, evaluation, and self-regulatory behavioral control, allowing for the specification of a neural model of race processing. We show how research on the neural correlates of race can serve to link otherwise disparate lines of evidence on the neural underpinnings of a broad array of social-cognitive phenomena, and consider implications for effecting change in race relations. PMID:19896410

  12. Neural Networks in Control Applications

    DEFF Research Database (Denmark)

    Sørensen, O.

    The intention of this report is to make a systematic examination of the possibilities of applying neural networks in those technical areas, which are familiar to a control engineer. In other words, the potential of neural networks in control applications is given higher priority than a detailed...... examined, and it appears that considering 'normal' neural network models with, say, 500 samples, the problem of over-fitting is neglible, and therefore it is not taken into consideration afterwards. Numerous model types, often met in control applications, are implemented as neural network models...... Kalmann filter) representing state space description. The potentials of neural networks for control of non-linear processes are also examined, focusing on three different groups of control concepts, all considered as generalizations of known linear control concepts to handle also non-linear processes...

  13. Impairment of mesenchymal stem cells derived from oral leukoplakia

    OpenAIRE

    Zhang, Zhihui; Song, Jiangyuan; Han, Ying; Mu, Dongdong; Su, Sha; Ji, Xiaoli; Liu, Hongwei

    2015-01-01

    Oral leukoplakia is one of the common precancerous lesions in oral mucosa. To compare the biological characteristics and regenerative capacities of mesenchymal stem cells (MSCs) from oral leukoplakia (epithelial hyperplasia and dysplasia) and normal oral mucosa, MSCs were isolated by enzyme digestion. Then these cells were identified by the expression of MSC related markers, STRO-1, CD105 and CD90, with the absent for the hematopoietic stem cell marker CD34 by flow cytometric detection. The s...

  14. Adipose tissue mesenchymal stromal cells as therapeutic vehicles against glioblastoma

    OpenAIRE

    Krasheninnikova, Maria Alieva

    2012-01-01

    Lately adipose tissue mesenchymal stem cells (hAMSCs) have emerged as cellular vehicles for therapy of solid tumors, due to their ease of isolation and manipulation, and wound/tumor homing capacity. HAMSCs have been successfully used in suicide gene therapy, employing the prodrug activating system based on Herpes simplex virus type I thymidine kinase (HSV-TK)/ganciclovir (GCV). In the current study we demonstrate an effective model of glioblastoma therapy based on the use of genetically modif...

  15. Research Advancements in Porcine Derived Mesenchymal Stem Cells

    OpenAIRE

    Bharti, Dinesh; Shivakumar, Sharath Belame; Subbarao, Raghavendra Baregundi; Rho, Gyu-Jin

    2016-01-01

    In the present era of stem cell biology, various animals such as Mouse, Bovine, Rabbit and Porcine have been tested for the efficiency of their mesenchymal stem cells (MSCs) before their actual use for stem cell based application in humans. Among them pigs have many similarities to humans in the form of organ size, physiology and their functioning, therefore they have been considered as a valuable model system for in vitro studies and preclinical assessments. Easy assessability, few ethical i...

  16. Mesenchymal Stem Cell-Mediated Functional Tooth Regeneration in Swine

    OpenAIRE

    Wataru Sonoyama; Yi Liu; Dianji Fang; Takayoshi Yamaza; Byoung-Moo Seo; Chunmei Zhang; He Liu; Stan Gronthos; Cun-Yu Wang; Songlin Wang; Songtao Shi

    2006-01-01

    Mesenchymal stem cell-mediated tissue regeneration is a promising approach for regenerative medicine for a wide range of applications. Here we report a new population of stem cells isolated from the root apical papilla of human teeth (SCAP, stem cells from apical papilla). Using a minipig model, we transplanted both human SCAP and periodontal ligament stem cells (PDLSCs) to generate a root/periodontal complex capable of supporting a porcelain crown, resulting in normal tooth function. This wo...

  17. The interaction between mesenchymal stem cells and steroids during inflammation

    OpenAIRE

    Chen, X; Gan, Y.; W. Li; Su, J.; Zhang, Y; Y. Huang; Roberts, A I; Han, Y; Li, J; Wang, Y.; Shi, Y

    2014-01-01

    Mesenchymal stem cells (MSCs) are believed to exert their regenerative effects through differentiation and modulation of inflammatory responses. However, the relationship between the severity of inflammation and stem cell-mediated tissue repair has not been formally investigated. In this study, we applied different concentrations of dexamethasone (Dex) to anti-CD3-activated splenocyte cultured with or without MSCs. As expected, Dex exhibited a classical dose-dependent inhibition of T-cell pro...

  18. Mesenchymal Stem Cells: Emerging Therapy for Duchenne Muscular Dystrophy

    OpenAIRE

    Markert, Chad; Atala, Anthony; Cann, Jennifer K.; Christ, George; Furth, Mark; Ambrosio, Fabrisia; Childers, Martin K.

    2009-01-01

    Multipotent cells that can give rise to bone, cartilage, fat, connective tissue, skeletal and cardiac muscle are termed mesenchymal stem cells (MSCs). These cells were first identified in the bone marrow, distinct from blood-forming stem cells. Based on the embryologic derivation, availability, and various pro-regenerative characteristics, research exploring their use in cell therapy shows great promise for patients with degenerative muscle diseases and a number of other conditions. In this r...

  19. Pericytes or Mesenchymal Stem Cells: Is That the Question?

    Science.gov (United States)

    Cano, Elena; Gebala, Véronique; Gerhardt, Holger

    2017-03-02

    For almost a decade, mesenchymal stem cells (MSCs) were believed to reside as perivascular cells in vivo. In this issue of Cell Stem Cell, Guimarães-Camboa et al. (2017) challenge this idea and use lineage tracing to demonstrate that perivascular cells do not behave as tissue-specific progenitors in various organs, despite showing MSC potential in vitro. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Mesenchymal stem cells: an alternative for bone regeneration

    OpenAIRE

    Franco-González, Lina María; Restrepo-Múnera, Luz Marina

    2014-01-01

    Mesenchymal Stem Cells (msc) are found in the bone marrow and have the capacity for self-renewal and differentiation in multiple lineages: osteogenic, condrogenic, adipogenic and thenogenic. They also serve as reservoirs involved in homeostasis, maintenance and cellular regeneration. Their application in bone alterations (traumatic defects, inflammatory and degenerative diseases) has led to the development of new osteo/conductive and/or inductive therapies. During the differentiation process ...

  1. Colorectal Mesenchymal Tumor: A Clinicopathologic Study of 25 Cases

    Directory of Open Access Journals (Sweden)

    Chen-Hui Lee

    2005-07-01

    Conclusion: Two clinicopathologically different categories were identified from our colorectal mesenchymal tumors: intramural GISTs and polypoid submucosal leiomyomas. Our study suggests that GIST is a better categorization than smooth muscle tumor because of the malignant potential. Prognosis is strictly related to the number of mitoses. However, tumor size, nuclear atypia and tumor necrosis are probably also significant predictive factors of lethality. Future studies with DNA analysis and larger patient numbers are essential to evaluate the prognostic significance of our findings.

  2. Development of mesenchymal subtype gene signature for clinical application in gastric cancer.

    Science.gov (United States)

    Lee, Jeeyun; Cristescu, Razvan; Kim, Kyoung-Mee; Kim, Kyung; Kim, Seung Tae; Park, Se Hoon; Kang, Won Ki

    2017-09-12

    Previously, in the Asian Cancer Research Group (ACRG) project, we defined four distinct molecular subtypes in gastric cancer (GC). Mesenchymal (microsatellite stable with epithelial-to-mesenchymal transition phenotype, MSS/EMT) tumors showed the worst prognosis among all the subtypes. To develop a gene signature for predicting mesenchymal subtype GC, we conducted gene expression profiling using a NanoString assay in 70 ACRG specimens. The gene signature was validated in an independent set obtained from the prospective Adjuvant chemoRadioTherapy In Stomach Tumor (ARTIST) trial. The association between the mesenchymal subtype and survival was investigated. After cross-platform concordance test performed in 70 ACRG specimens, a 71-gene MSS/EMT signature was obtained. In the validation set, the gene signature predicted that 20 of 73 (27%) patients had mesenchymal tumors. Patients with mesenchymal subtype had diffuse GC, poorly-differentiated or signet ring cell carcinoma, and were microsatellite stable. The estimated hazard ratio for survival in patients with mesenchymal GC compared to those with non-mesenchymal tumors was 2.262 (95% confidence interval, 1.410 to 3.636; P=0.001). The survival difference remained significant when the subtypes were analyzed according to clinical prognostic parameters. This study suggested that the NanoString-based 71-gene signature for mesenchymal subtype is a strong predictor of the outcome in patients with GC.

  3. Exosomes derived from mesenchymal non-small cell lung cancer cells promote chemoresistance.

    Science.gov (United States)

    Lobb, Richard J; van Amerongen, Rosa; Wiegmans, Adrian; Ham, Sunyoung; Larsen, Jill E; Möller, Andreas

    2017-08-01

    Non-small cell lung cancer (NSCLC) is the most common lung cancer type and the most common cause of mortality in lung cancer patients. NSCLC is often associated with resistance to chemotherapeutics and together with rapid metastatic spread, results in limited treatment options and poor patient survival. NSCLCs are heterogeneous, and consist of epithelial and mesenchymal NSCLC cells. Mesenchymal NSCLC cells are thought to be responsible for the chemoresistance phenotype, but if and how this phenotype can be transferred to other NSCLC cells is currently not known. We hypothesised that small extracellular vesicles, exosomes, secreted by mesenchymal NSCLC cells could potentially transfer the chemoresistance phenotype to surrounding epithelial NSCLC cells. To explore this possibility, we used a unique human bronchial epithelial cell (HBEC) model in which the parental cells were transformed from an epithelial to mesenchymal phenotype by introducing oncogenic alterations common in NSCLC. We found that exosomes derived from the oncogenically transformed, mesenchymal HBECs could transfer chemoresistance to the parental, epithelial HBECs and increase ZEB1 mRNA, a master EMT transcription factor, in the recipient cells. Additionally, we demonstrate that exosomes from mesenchymal, but not epithelial HBECs contain the ZEB1 mRNA, thereby providing a potential mechanism for the induction of a mesenchymal phenotype in recipient cells. Together, this work demonstrates for the first time that exosomes derived from mesenchymal, oncogenically transformed lung cells can transfer chemoresistance and mesenchymal phenotypes to recipient cells, likely via the transfer of ZEB1 mRNA in exosomes. © 2017 UICC.

  4. Endothelial to mesenchymal transition in the cardiovascular system.

    Science.gov (United States)

    Gong, Hui; Lyu, Xing; Wang, Qiong; Hu, Min; Zhang, Xiangyu

    2017-09-01

    Endothelial to mesenchymal transition (EndMT) is a special type of epithelial to mesenchymal transition. It is a process that is characterized by the loss of features of endothelial cells and acquisition of specific markers of mesenchymal cells. A variety of stimuli, such as inflammation, growth factors, and hypoxia, regulate EndMT through various signaling pathways and intracellular transcription factors. It has been demonstrated that epigenetic modifications are also involved in this process. Recent studies have identified the essential role of EndMT in the cardiovascular system. EndMT contributes to steps in cardiovascular development, such as cardiac valve formation and septation, as well as the pathogenesis of various cardiovascular disorders, such as congenital heart disease, myocardial fibrosis, myocardial infarction and pulmonary arterial hypertension. Thus, comprehensive understanding of the underlying mechanisms of EndMT will provide novel therapeutic strategies to overcome congenital heart disease due to abnormal development and other cardiovascular diseases. This review will focus on summarizing the currently understood signaling pathways and epigenetic modifications involved in the regulation of EndMT and the role of EndMT in pathophysiological conditions of the cardiovascular system. Copyright © 2017. Published by Elsevier Inc.

  5. MicroRNA Regulation of Epithelial to Mesenchymal Transition

    Directory of Open Access Journals (Sweden)

    Mohammed L. Abba

    2016-01-01

    Full Text Available Epithelial to mesenchymal transition (EMT is a central regulatory program that is similar in many aspects to several steps of embryonic morphogenesis. In addition to its physiological role in tissue repair and wound healing, EMT contributes to chemo resistance, metastatic dissemination and fibrosis, amongst others. Classically, the morphological change from epithelial to mesenchymal phenotype is characterized by the appearance or loss of a group of proteins which have come to be recognized as markers of the EMT process. As with all proteins, these molecules are controlled at the transcriptional and translational level by transcription factors and microRNAs, respectively. A group of developmental transcription factors form the backbone of the EMT cascade and a large body of evidence shows that microRNAs are heavily involved in the successful coordination of mesenchymal transformation and vice versa, either by suppressing the expression of different groups of transcription factors, or otherwise acting as their functional mediators in orchestrating EMT. This article dissects the contribution of microRNAs to EMT and analyzes the molecular basis for their roles in this cellular process. Here, we emphasize their interaction with core transcription factors like the zinc finger enhancer (E-box binding homeobox (ZEB, Snail and Twist families as well as some pluripotency transcription factors.

  6. Oral lining mucosa development depends on mesenchymal microRNAs.

    Science.gov (United States)

    Otsuka-Tanaka, Y; Oommen, S; Kawasaki, M; Kawasaki, K; Imam, N; Jalani-Ghazani, F; Hindges, R; Sharpe, P T; Ohazama, A

    2013-03-01

    The oral mucosa plays critical roles in protection, sensation, and secretion and can be classified into masticatory, lining, and specialized mucosa that are known to be functionally, histologically, and clinically distinct. Each type of oral mucosa is believed to develop through discrete molecular mechanisms, which remain unclear. MicroRNAs (miRNAs) are 19 to 25nt non-coding small single-stranded RNAs that negatively regulate gene expression by binding target mRNAs. miRNAs are crucial for fine-tuning of molecular mechanisms. To investigate the role of miRNAs in oral mucosa development, we examined mice with mesenchymal (Wnt1Cre;Dicer(fl/fl)) conditional deletion of Dicer. Wnt1Cre;Dicer(fl/fl) mice showed trans-differentiation of lining mucosa into an epithelium with masticatory mucosa/ skin-specific characteristics. Up-regulation of Fgf signaling was found in mutant lining mucosal epithelium that was accompanied by an increase in Fgf7 expression in mutant mesenchyme. Mesenchyme miRNAs thus have an indirect effect on lining mucosal epithelial cell growth/differentiation.

  7. Research Advancements in Porcine Derived Mesenchymal Stem Cells.

    Science.gov (United States)

    Bharti, Dinesh; Shivakumar, Sharath Belame; Subbarao, Raghavendra Baregundi; Rho, Gyu-Jin

    2016-01-01

    In the present era of stem cell biology, various animals such as Mouse, Bovine, Rabbit and Porcine have been tested for the efficiency of their mesenchymal stem cells (MSCs before their actual use for stem cell based application in humans. Among them pigs have many similarities to humans in the form of organ size, physiology and their functioning, therefore they have been considered as a valuable model system for in vitro studies and preclinical assessments. Easy assessability, few ethical issues, successful MSC isolation from different origins like bone marrow, skin, umbilical cord blood, Wharton's jelly, endometrium, amniotic fluid and peripheral blood make porcine a good model for stem cell therapy. Porcine derived MSCs (pMSCs have shown greater in vitro differentiation and transdifferention potential towards mesenchymal lineages and specialized lineages such as cardiomyocytes, neurons, hepatocytes and pancreatic beta cells. Immunomodulatory and low immunogenic profiles as shown by autologous and heterologous MSCs proves them safe and appropriate models for xenotransplantation purposes. Furthermore, tissue engineered stem cell constructs can be of immense importance in relation to various osteochondral defects which are difficult to treat otherwise. Using pMSCs successful treatment of various disorders like Parkinson's disease, cardiac ischemia, hepatic failure, has been reported by many studies. Here, in this review we highlight current research findings in the area of porcine mesenchymal stem cells dealing with their isolation methods, differentiation ability, transplantation applications and their therapeutic potential towards various diseases.

  8. Epithelial-mesenchymal transition in tissue repair and fibrosis.

    Science.gov (United States)

    Stone, Rivka C; Pastar, Irena; Ojeh, Nkemcho; Chen, Vivien; Liu, Sophia; Garzon, Karen I; Tomic-Canic, Marjana

    2016-09-01

    The epithelial-mesenchymal transition (EMT) describes the global process by which stationary epithelial cells undergo phenotypic changes, including the loss of cell-cell adhesion and apical-basal polarity, and acquire mesenchymal characteristics that confer migratory capacity. EMT and its converse, MET (mesenchymal-epithelial transition), are integral stages of many physiologic processes and, as such, are tightly coordinated by a host of molecular regulators. Converging lines of evidence have identified EMT as a component of cutaneous wound healing, during which otherwise stationary keratinocytes (the resident skin epithelial cells) migrate across the wound bed to restore the epidermal barrier. Moreover, EMT plays a role in the development of scarring and fibrosis, as the matrix-producing myofibroblasts arise from cells of the epithelial lineage in response to injury but are pathologically sustained instead of undergoing MET or apoptosis. In this review, we summarize the role of EMT in physiologic repair and pathologic fibrosis of tissues and organs. We conclude that further investigation into the contribution of EMT to the faulty repair of fibrotic wounds might identify components of EMT signaling as common therapeutic targets for impaired healing in many tissues. Graphical Abstract Model for injury-triggered EMT activation in physiologic wound repair (left) and fibrotic wound healing (right).

  9. Primary Extraskeletal Mesenchymal Chondrosarcoma Arising from the Pancreas

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Bae Geun; Han, Yoon Hee; Lee, Byung Hoon; Kim, Su Young; Hwang, Yoon Joon; Seo, Jung Wook; Kim, Yong Hoon; Cha, Soon Joo; Hur, Gham; Joo, Mee [Inje University, School of Medicine, Goyang (Korea, Republic of)

    2007-12-15

    The CT scans showed a heterogeneously enhancing necrotic mass with numerous areas of coarse calcification, and this was located in the left side of the retroperitoneal space and involved the body and tail of the pancreas. Portal venography via the celiac axis also showed invasion of the splenic vein. It represents approximately 1% of all chondrosarcomas and it carries a poor prognosis. It can occur in extraskeletal locations and mainly in the soft tissues of the orbit, the cranial and spinal meningeal coverings and the lower limbs. To the best of our knowledge, there has been no reported case of primary extraskeletal mesenchymal chondrosarcoma of the pancreas. Only two instances of metastatic chondrosarcomas in the pancreas have been reported in the literature. We report here on a case of primary mesenchymal chondrosarcoma arising from the pancreas in a 41-year-old man. In summary, we present here a case of primary extraskeletal mesenchymal chondrosarcoma that arose from the pancreas. Radiologically, it manifested as a necrotic soft tissue mass with chondroid calcifications.

  10. Research Advancements in Porcine Derived Mesenchymal Stem Cells

    Science.gov (United States)

    Bharti, Dinesh; Shivakumar, Sharath Belame; Subbarao, Raghavendra Baregundi; Rho, Gyu-Jin

    2016-01-01

    In the present era of stem cell biology, various animals such as Mouse, Bovine, Rabbit and Porcine have been tested for the efficiency of their mesenchymal stem cells (MSCs) before their actual use for stem cell based application in humans. Among them pigs have many similarities to humans in the form of organ size, physiology and their functioning, therefore they have been considered as a valuable model system for in vitro studies and preclinical assessments. Easy assessability, few ethical issues, successful MSC isolation from different origins like bone marrow, skin, umbilical cord blood, Wharton’s jelly, endometrium, amniotic fluid and peripheral blood make porcine a good model for stem cell therapy. Porcine derived MSCs (pMSCs) have shown greater in vitro differentiation and transdifferention potential towards mesenchymal lineages and specialized lineages such as cardiomyocytes, neurons, hepatocytes and pancreatic beta cells. Immunomodulatory and low immunogenic profiles as shown by autologous and heterologous MSCs proves them safe and appropriate models for xenotransplantation purposes. Furthermore, tissue engineered stem cell constructs can be of immense importance in relation to various osteochondral defects which are difficult to treat otherwise. Using pMSCs successful treatment of various disorders like Parkinson’s disease, cardiac ischemia, hepatic failure, has been reported by many studies. Here, in this review we highlight current research findings in the area of porcine mesenchymal stem cells dealing with their isolation methods, differentiation ability, transplantation applications and their therapeutic potential towards various diseases. PMID:26201864

  11. An Optoelectronic Neural Network

    Science.gov (United States)

    Neil, Mark A. A.; White, Ian H.; Carroll, John E.

    1990-02-01

    We describe and present results of an optoelectronic neural network processing system. The system uses an algorithm based on the Hebbian learning rule to memorise a set of associated vector pairs. Recall occurs by the processing of the input vector with these stored associations in an incoherent optical vector multiplier using optical polarisation rotating liquid crystal spatial light modulators to store the vectors and an optical polarisation shadow casting technique to perform multiplications. Results are detected on a photodiode array and thresholded electronically by a controlling microcomputer. The processor is shown to work in autoassociative and heteroassociative modes with up to 10 stored memory vectors of length 64 (equivalent to 64 neurons) and a cycle time of 50ms. We discuss the limiting factors at work in this system, how they affect its scalability and the general applicability of its principles to other systems.

  12. Neural Darwinism and consciousness.

    Science.gov (United States)

    Seth, Anil K; Baars, Bernard J

    2005-03-01

    Neural Darwinism (ND) is a large scale selectionist theory of brain development and function that has been hypothesized to relate to consciousness. According to ND, consciousness is entailed by reentrant interactions among neuronal populations in the thalamocortical system (the 'dynamic core'). These interactions, which permit high-order discriminations among possible core states, confer selective advantages on organisms possessing them by linking current perceptual events to a past history of value-dependent learning. Here, we assess the consistency of ND with 16 widely recognized properties of consciousness, both physiological (for example, consciousness is associated with widespread, relatively fast, low amplitude interactions in the thalamocortical system), and phenomenal (for example, consciousness involves the existence of a private flow of events available only to the experiencing subject). While no theory accounts fully for all of these properties at present, we find that ND and its recent extensions fare well.

  13. Cortical neural prosthetics.

    Science.gov (United States)

    Schwartz, Andrew B

    2004-01-01

    Control of prostheses using cortical signals is based on three elements: chronic microelectrode arrays, extraction algorithms, and prosthetic effectors. Arrays of microelectrodes are permanently implanted in cerebral cortex. These arrays must record populations of single- and multiunit activity indefinitely. Information containing position and velocity correlates of animate movement needs to be extracted continuously in real time from the recorded activity. Prosthetic arms, the current effectors used in this work, need to have the agility and configuration of natural arms. Demonstrations using closed-loop control show that subjects change their neural activity to improve performance with these devices. Adaptive-learning algorithms that capitalize on these improvements show that this technology has the capability of restoring much of the arm movement lost with immobilizing deficits.

  14. Odd-skipped related genes regulate differentiation of embryonic limb mesenchyme and bone marrow mesenchymal stromal cells.

    Science.gov (United States)

    Stricker, Sigmar; Mathia, Susanne; Haupt, Julia; Seemann, Petra; Meier, Julia; Mundlos, Stefan

    2012-03-01

    The regulation of progenitor cell differentiation to a specific tissue type is one of the fundamental questions of biology. Here, we identify Osr1 and Osr2, 2 closely related genes encoding zinc finger transcription factors, as being strongly expressed in irregular connective tissue (ICT) fibroblasts in the chicken embryo, suitable as a developmental marker. We provide evidence that both Osr1 and Osr2 regulate mesenchymal cell-type differentiation. Both Osr1 and Osr2 can promote the formation of ICT, a cell type of so far unknown molecular specification, while suppressing differentiation of other tissues such as cartilage and tendon from uncommitted progenitors. Conversely, knockdown of either Osr gene alone or in combination reverses this effect, thereby leading to decreased differentiation of ICT fibroblasts and increased chondrogenesis in vitro. This indicates that Osr genes play a pivotal role in ICT fibroblast differentiation. Undifferentiated mesenchymal cells reside in the adult body in the form of mesenchymal stem cells in the bone marrow cavity. Using bone marrow stromal cells (BMSCs) isolated from chicken fetal long bones, we show that Osr1 and Osr2 have an intrinsic role in BMSC differentiation similar to their role in early embryonic development, that is, the enforcement of CT fibroblast differentiation and the repression of other cell types as exemplified here by osteoblast differentiation.

  15. In vitro induction and differentiation of umbilical cord mesenchymal stem cells into neuron-like cells by all-trans retinoic acid

    Directory of Open Access Journals (Sweden)

    Wei Jin

    2015-04-01

    Full Text Available AIM: To determine the optimal concentration for inducing the differentiation of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs into neuron-like cells, although it is understood that all-trans retinoic acid (ATRA regulates cell proliferation in the nervous system by modulating the balance between mitosis and apoptosis. METHODS: The abilities of ATRA to promote apoptosis as well as neural differentiation were assessed in cultured hUC-MSCs by morphological observation, MTT assay, annexin V-FITC/PI flow cytometry and immunocytochemistry. RESULTS: The data showed that low concentrations of ATRA (0.5 µmol, 0.25 µmol had no effect on the number of cells. However, treatment with 1.0 µmol or 2.0 µmol ATRA induced a 24.16% and 52.67% reduction in cell number, respectively, compared with vehicle-treated cultures. Further, 4.0 µmol ATRA had a potent effect on cell number, with almost no adherent cells recovered after 24h. We further showed that 0.5 µmol ATRA caused these cells to express characteristic markers of neuronal progenitor cells. CONCLUSION: Taken together, we conclude that ATRA has a dose-dependent influence on the neural differentiation and apoptosis of hUC-MSCs. These findings have implications on the use of ATRA-differentiated hUC-MSCs for the study of neural degeneration diseases.

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  19. Cooperating attackers in neural cryptography.

    Science.gov (United States)

    Shacham, Lanir N; Klein, Einat; Mislovaty, Rachel; Kanter, Ido; Kinzel, Wolfgang

    2004-06-01

    A successful attack strategy in neural cryptography is presented. The neural cryptosystem, based on synchronization of neural networks by mutual learning, has been recently shown to be secure under different attack strategies. The success of the advanced attacker presented here, called the "majority-flipping attacker," does not decay with the parameters of the model. This attacker's outstanding success is due to its using a group of attackers which cooperate throughout the synchronization process, unlike any other attack strategy known. An analytical description of this attack is also presented, and fits the results of simulations.

  20. Cooperating attackers in neural cryptography

    Science.gov (United States)

    Shacham, Lanir N.; Klein, Einat; Mislovaty, Rachel; Kanter, Ido; Kinzel, Wolfgang

    2004-06-01

    A successful attack strategy in neural cryptography is presented. The neural cryptosystem, based on synchronization of neural networks by mutual learning, has been recently shown to be secure under different attack strategies. The success of the advanced attacker presented here, called the “majority-flipping attacker,” does not decay with the parameters of the model. This attacker’s outstanding success is due to its using a group of attackers which cooperate throughout the synchronization process, unlike any other attack strategy known. An analytical description of this attack is also presented, and fits the results of simulations.

  1. Neural Computations in Binaural Hearing

    Science.gov (United States)

    Wagner, Hermann

    Binaural hearing helps humans and animals to localize and unmask sounds. Here, binaural computations in the barn owl's auditory system are discussed. Barn owls use the interaural time difference (ITD) for azimuthal sound localization, and they use the interaural level difference (ELD) for elevational sound localization. ITD and ILD and their precursors are processed in separate neural pathways, the time pathway and the intensity pathway, respectively. Representation of ITD involves four main computational steps, while the representation of ILD is accomplished in three steps. In the discussion neural processing in the owl's auditory system is compared with neural computations present in mammals.

  2. Neural Manifolds for the Control of Movement.

    Science.gov (United States)

    Gallego, Juan A; Perich, Matthew G; Miller, Lee E; Solla, Sara A

    2017-06-07

    The analysis of neural dynamics in several brain cortices has consistently uncovered low-dimensional manifolds that capture a significant fraction of neural variability. These neural manifolds are spanned by specific patterns of correlated neural activity, the "neural modes." We discuss a model for neural control of movement in which the time-dependent activation of these neural modes is the generator of motor behavior. This manifold-based view of motor cortex may lead to a better understanding of how the brain controls movement. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Human Adipose Tissue-Derived Mesenchymal Stem Cells Target Brain Tumor-Initiating Cells.

    Science.gov (United States)

    Choi, Seung Ah; Lee, Ji Yeoun; Kwon, Sung Eun; Wang, Kyu-Chang; Phi, Ji Hoon; Choi, Jung Won; Jin, Xiong; Lim, Ja Yun; Kim, Hyunggee; Kim, Seung-Ki

    2015-01-01

    In neuro-oncology, the biology of neural stem cells (NSCs) has been pursued in two ways: as tumor-initiating cells (TICs) and as a potential cell-based vehicle for gene therapy. NSCs as well as mesenchymal stem cells (MSCs) have been reported to possess tumor tropism capacities. However, there is little data on the migratory capacity of MSCs toward brain tumor-initiating cells (BTICs). This study focuses on the ability of human adipose tissue derived MSCs (hAT-MSCs) to target BTICs and their crosstalk in the microenvironment. BTICs were isolated from three different types of brain tumors. The migration capacities of hAT-MSCs toward BTICs were examined using an in vitro migration assay and in vivo bioluminescence imaging analysis. To investigate the crosstalk between hAT-MSCs and BTICs, we analyzed the mRNA expression patterns of cyto-chemokine receptors by RT-qPCR and the protein level of their ligands in co-cultured medium. The candidate cyto-chemokine receptors were selectively inhibited using siRNAs. Both in vitro and in vivo experiments showed that hAT-MSCs possess migratory abilities to target BTICs isolated from medulloblastoma, atypical teratoid/rhabdoid tumors (AT/RT) and glioblastoma. Different types of cyto-chemokines are involved in the crosstalk between hAT-MSCs and BTICs (medulloblastoma and AT/RT: CXCR4/SDF-1, CCR5/RANTES, IL6R/IL-6 and IL8R/IL8; glioblastoma: CXCR4/SDF-1, IL6R/IL-6, IL8R/IL-8 and IGF1R/IGF-1). Our findings demonstrated the migratory ability of hAT-MSCs for BTICs, implying the potential use of MSCs as a delivery vehicle for gene therapy. This study also confirmed the expression of hAT-MSCs cytokine receptors and the BTIC ligands that play roles in their crosstalk.

  4. Femtosecond laser pulses for chemical-free embryonic and mesenchymal stem cell differentiation

    Science.gov (United States)

    Mthunzi, Patience; Dholakia, Kishan; Gunn-Moore, Frank

    2011-10-01

    Owing to their self renewal and pluripotency properties, stem cells can efficiently advance current therapies in tissue regeneration and/or engineering. Under appropriate culture conditions in vitro, pluripotent stem cells can be primed to differentiate into any cell type some examples including neural, cardiac and blood cells. However, there still remains a pressing necessity to answer the biological questions concerning how stem cell renewal and how differentiation programs are operated and regulated at the genetic level. In stem cell research, an urgent requirement on experimental procedures allowing non-invasive, marker-free observation of growth, proliferation and stability of living stem cells under physiological conditions exists. Femtosecond (fs) laser pulses have been reported to non-invasively deliver exogenous materials, including foreign genetic species into both multipotent and pluripotent stem cells successfully. Through this multi-photon facilitated technique, directly administering fs laser pulses onto the cell plasma membrane induces transient submicrometer holes, thereby promoting cytosolic uptake of the surrounding extracellular matter. To display a chemical-free cell transfection procedure that utilises micro-litre scale volumes of reagents, we report for the first time on 70 % transfection efficiency in ES-E14TG2a cells using the enhanced green fluorescing protein (EGFP) DNA plasmid. We also show how varying the average power output during optical transfection influences cell viability, proliferation and cytotoxicity in embryonic stem cells. The impact of utilizing objective lenses of different numerical aperture (NA) on the optical transfection efficiency in ES-E14TG2a cells is presented. Finally, we report on embryonic and mesenchymal stem cell differentiation. The produced specialized cell types could thereafter be characterized and used for cell based therapies.

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  6. File list: NoD.Oth.10.AllAg.Mesenchymal_stem_cells [Chip-atlas[Archive

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    Full Text Available NoD.Oth.10.AllAg.Mesenchymal_stem_cells hg19 No description Others Mesenchymal stem...RX302073,ERX302070,ERX302072,ERX302074 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/NoD.Oth.10.AllAg.Mesenchymal_stem_cells.bed ...

  7. File list: Pol.Adp.50.AllAg.Adipose-Derived_Mesenchymal_Stem_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Adp.50.AllAg.Adipose-Derived_Mesenchymal_Stem_Cells hg19 RNA polymerase Adipocyte Adipose-Derived... Mesenchymal Stem Cells http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Adp.50.AllAg.Adipose-Derived_Mesenchymal_Stem_Cells.bed ...

  8. File list: Unc.Adp.05.AllAg.Adipose-Derived_Mesenchymal_Stem_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Adp.05.AllAg.Adipose-Derived_Mesenchymal_Stem_Cells hg19 Unclassified Adipocyte Adipose-Derived... Mesenchymal Stem Cells http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Unc.Adp.05.AllAg.Adipose-Derived_Mesenchymal_Stem_Cells.bed ...

  9. File list: DNS.Adp.10.AllAg.Adipose-Derived_Mesenchymal_Stem_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Adp.10.AllAg.Adipose-Derived_Mesenchymal_Stem_Cells hg19 DNase-seq Adipocyte Adipose-Derived... Mesenchymal Stem Cells SRX660076,SRX660075 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/DNS.Adp.10.AllAg.Adipose-Derived_Mesenchymal_Stem_Cells.bed ...

  10. File list: Pol.Adp.20.AllAg.Adipose-Derived_Mesenchymal_Stem_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Adp.20.AllAg.Adipose-Derived_Mesenchymal_Stem_Cells hg19 RNA polymerase Adipocyte Adipose-Derived... Mesenchymal Stem Cells http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Adp.20.AllAg.Adipose-Derived_Mesenchymal_Stem_Cells.bed ...

  11. File list: Pol.Adp.10.AllAg.Adipose-Derived_Mesenchymal_Stem_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Adp.10.AllAg.Adipose-Derived_Mesenchymal_Stem_Cells hg19 RNA polymerase Adipocyte Adipose-Derived... Mesenchymal Stem Cells http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Adp.10.AllAg.Adipose-Derived_Mesenchymal_Stem_Cells.bed ...

  12. File list: Unc.Adp.10.AllAg.Adipose-Derived_Mesenchymal_Stem_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Adp.10.AllAg.Adipose-Derived_Mesenchymal_Stem_Cells hg19 Unclassified Adipocyte Adipose-Derived... Mesenchymal Stem Cells http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Unc.Adp.10.AllAg.Adipose-Derived_Mesenchymal_Stem_Cells.bed ...

  13. File list: Unc.Adp.20.AllAg.Adipose-Derived_Mesenchymal_Stem_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Adp.20.AllAg.Adipose-Derived_Mesenchymal_Stem_Cells hg19 Unclassified Adipocyte Adipose-Derived... Mesenchymal Stem Cells http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Unc.Adp.20.AllAg.Adipose-Derived_Mesenchymal_Stem_Cells.bed ...

  14. File list: Pol.Adp.05.AllAg.Adipose-Derived_Mesenchymal_Stem_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Adp.05.AllAg.Adipose-Derived_Mesenchymal_Stem_Cells hg19 RNA polymerase Adipocyte Adipose-Derived... Mesenchymal Stem Cells http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Adp.05.AllAg.Adipose-Derived_Mesenchymal_Stem_Cells.bed ...

  15. File list: NoD.Adp.20.AllAg.Adipose-Derived_Mesenchymal_Stem_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Adp.20.AllAg.Adipose-Derived_Mesenchymal_Stem_Cells hg19 No description Adipocyte Adipose-Derived... Mesenchymal Stem Cells SRX312175,SRX312171 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/NoD.Adp.20.AllAg.Adipose-Derived_Mesenchymal_Stem_Cells.bed ...

  16. File list: InP.Adp.20.AllAg.Adipose-Derived_Mesenchymal_Stem_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Adp.20.AllAg.Adipose-Derived_Mesenchymal_Stem_Cells hg19 Input control Adipocyte Adipose-Derived... Mesenchymal Stem Cells SRX660092,SRX660091 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/InP.Adp.20.AllAg.Adipose-Derived_Mesenchymal_Stem_Cells.bed ...

  17. File list: InP.Adp.05.AllAg.Adipose-Derived_Mesenchymal_Stem_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Adp.05.AllAg.Adipose-Derived_Mesenchymal_Stem_Cells hg19 Input control Adipocyte Adipose-Derived... Mesenchymal Stem Cells SRX660092,SRX660091 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/InP.Adp.05.AllAg.Adipose-Derived_Mesenchymal_Stem_Cells.bed ...

  18. File list: NoD.Adp.50.AllAg.Adipose-Derived_Mesenchymal_Stem_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Adp.50.AllAg.Adipose-Derived_Mesenchymal_Stem_Cells hg19 No description Adipocyte Adipose-Derived... Mesenchymal Stem Cells SRX312175,SRX312171 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/NoD.Adp.50.AllAg.Adipose-Derived_Mesenchymal_Stem_Cells.bed ...

  19. File list: DNS.Adp.50.AllAg.Adipose-Derived_Mesenchymal_Stem_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Adp.50.AllAg.Adipose-Derived_Mesenchymal_Stem_Cells hg19 DNase-seq Adipocyte Adipose-Derived... Mesenchymal Stem Cells SRX660075,SRX660076 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/DNS.Adp.50.AllAg.Adipose-Derived_Mesenchymal_Stem_Cells.bed ...

  20. File list: NoD.Adp.10.AllAg.Adipose-Derived_Mesenchymal_Stem_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Adp.10.AllAg.Adipose-Derived_Mesenchymal_Stem_Cells hg19 No description Adipocyte Adipose-Derived... Mesenchymal Stem Cells SRX312175,SRX312171 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/NoD.Adp.10.AllAg.Adipose-Derived_Mesenchymal_Stem_Cells.bed ...

  1. File list: InP.Adp.10.AllAg.Adipose-Derived_Mesenchymal_Stem_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Adp.10.AllAg.Adipose-Derived_Mesenchymal_Stem_Cells hg19 Input control Adipocyte Adipose-Derived... Mesenchymal Stem Cells SRX660092,SRX660091 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/InP.Adp.10.AllAg.Adipose-Derived_Mesenchymal_Stem_Cells.bed ...

  2. File list: InP.Adp.50.AllAg.Adipose-Derived_Mesenchymal_Stem_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Adp.50.AllAg.Adipose-Derived_Mesenchymal_Stem_Cells hg19 Input control Adipocyte Adipose-Derived... Mesenchymal Stem Cells SRX660091,SRX660092 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/InP.Adp.50.AllAg.Adipose-Derived_Mesenchymal_Stem_Cells.bed ...

  3. File list: Unc.Adp.50.AllAg.Adipose-Derived_Mesenchymal_Stem_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Adp.50.AllAg.Adipose-Derived_Mesenchymal_Stem_Cells hg19 Unclassified Adipocyte Adipose-Derived... Mesenchymal Stem Cells http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Unc.Adp.50.AllAg.Adipose-Derived_Mesenchymal_Stem_Cells.bed ...

  4. File list: DNS.Adp.20.AllAg.Adipose-Derived_Mesenchymal_Stem_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Adp.20.AllAg.Adipose-Derived_Mesenchymal_Stem_Cells hg19 DNase-seq Adipocyte Adipose-Derived... Mesenchymal Stem Cells SRX660076,SRX660075 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/DNS.Adp.20.AllAg.Adipose-Derived_Mesenchymal_Stem_Cells.bed ...

  5. File list: NoD.Adp.05.AllAg.Adipose-Derived_Mesenchymal_Stem_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Adp.05.AllAg.Adipose-Derived_Mesenchymal_Stem_Cells hg19 No description Adipocyte Adipose-Derived... Mesenchymal Stem Cells SRX312175,SRX312171 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/NoD.Adp.05.AllAg.Adipose-Derived_Mesenchymal_Stem_Cells.bed ...

  6. File list: DNS.Adp.05.AllAg.Adipose-Derived_Mesenchymal_Stem_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Adp.05.AllAg.Adipose-Derived_Mesenchymal_Stem_Cells hg19 DNase-seq Adipocyte Adipose-Derived... Mesenchymal Stem Cells SRX660076,SRX660075 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/DNS.Adp.05.AllAg.Adipose-Derived_Mesenchymal_Stem_Cells.bed ...

  7. File list: InP.Oth.10.AllAg.Mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Oth.10.AllAg.Mesenchymal_stem_cells mm9 Input control Others Mesenchymal stem c...ells SRX318104,SRX318102,SRX228660,SRX228662,SRX228663,SRX228661 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Oth.10.AllAg.Mesenchymal_stem_cells.bed ...

  8. File list: NoD.Oth.05.AllAg.Mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Oth.05.AllAg.Mesenchymal_stem_cells mm9 No description Others Mesenchymal stem ...cells SRX694677,SRX694678 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Oth.05.AllAg.Mesenchymal_stem_cells.bed ...

  9. File list: NoD.Oth.50.AllAg.Mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Oth.50.AllAg.Mesenchymal_stem_cells hg19 No description Others Mesenchymal stem...RX302074,ERX302075,ERX302066,ERX302072 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/NoD.Oth.50.AllAg.Mesenchymal_stem_cells.bed ...

  10. File list: NoD.Oth.20.AllAg.Mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Oth.20.AllAg.Mesenchymal_stem_cells hg19 No description Others Mesenchymal stem...RX302072,ERX302066,ERX302075,ERX302074 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/NoD.Oth.20.AllAg.Mesenchymal_stem_cells.bed ...

  11. File list: NoD.Oth.50.AllAg.Mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Oth.50.AllAg.Mesenchymal_stem_cells mm9 No description Others Mesenchymal stem ...cells SRX694677,SRX694678 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Oth.50.AllAg.Mesenchymal_stem_cells.bed ...

  12. File list: InP.CDV.10.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.CDV.10.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells hg19 Input control C...bc.jp/kyushu-u/hg19/assembled/InP.CDV.10.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells.bed ... ...ardiovascular Umbilical cord-derived mesenchymal stem cells SRX831247,SRX831246 http://dbarchive.bioscienced

  13. File list: Pol.CDV.10.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.CDV.10.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells hg19 RNA polymerase ...Cardiovascular Umbilical cord-derived mesenchymal stem cells http://dbarchive.biosciencedbc.jp/kyushu-u/hg19.../assembled/Pol.CDV.10.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells.bed ...

  14. File list: Unc.CDV.10.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.CDV.10.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells hg19 Unclassified Ca...ssembled/Unc.CDV.10.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells.bed ... ...rdiovascular Umbilical cord-derived mesenchymal stem cells http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/a

  15. File list: ALL.CDV.05.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.CDV.05.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells hg19 All antigens Ca...biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.CDV.05.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells.bed ... ...rdiovascular Umbilical cord-derived mesenchymal stem cells SRX831253,SRX831250,SRX831252,SRX831249,SRX831251

  16. File list: Pol.CDV.05.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.CDV.05.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells hg19 RNA polymerase ...Cardiovascular Umbilical cord-derived mesenchymal stem cells http://dbarchive.biosciencedbc.jp/kyushu-u/hg19.../assembled/Pol.CDV.05.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells.bed ...

  17. File list: Unc.CDV.50.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.CDV.50.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells hg19 Unclassified Ca...ssembled/Unc.CDV.50.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells.bed ... ...rdiovascular Umbilical cord-derived mesenchymal stem cells http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/a

  18. File list: DNS.CDV.50.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.CDV.50.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells hg19 DNase-seq Cardiovascular Umbilical cord...-derived mesenchymal stem cells http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/DNS.CDV.50.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells.bed ...

  19. File list: Oth.CDV.05.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.CDV.05.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells hg19 TFs and others ...Cardiovascular Umbilical cord-derived mesenchymal stem cells http://dbarchive.biosciencedbc.jp/kyushu-u/hg19.../assembled/Oth.CDV.05.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells.bed ...

  20. File list: Oth.CDV.20.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.CDV.20.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells hg19 TFs and others ...Cardiovascular Umbilical cord-derived mesenchymal stem cells http://dbarchive.biosciencedbc.jp/kyushu-u/hg19.../assembled/Oth.CDV.20.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells.bed ...

  1. File list: DNS.CDV.20.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.CDV.20.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells hg19 DNase-seq Cardiovascular Umbilical cord...-derived mesenchymal stem cells http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/DNS.CDV.20.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells.bed ...

  2. File list: Oth.CDV.10.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.CDV.10.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells hg19 TFs and others ...Cardiovascular Umbilical cord-derived mesenchymal stem cells http://dbarchive.biosciencedbc.jp/kyushu-u/hg19.../assembled/Oth.CDV.10.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells.bed ...

  3. File list: InP.CDV.50.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.CDV.50.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells hg19 Input control C...bc.jp/kyushu-u/hg19/assembled/InP.CDV.50.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells.bed ... ...ardiovascular Umbilical cord-derived mesenchymal stem cells SRX831247,SRX831246 http://dbarchive.bioscienced

  4. File list: InP.CDV.05.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.CDV.05.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells hg19 Input control C...bc.jp/kyushu-u/hg19/assembled/InP.CDV.05.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells.bed ... ...ardiovascular Umbilical cord-derived mesenchymal stem cells SRX831247,SRX831246 http://dbarchive.bioscienced

  5. File list: NoD.CDV.50.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.CDV.50.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells hg19 No description ...Cardiovascular Umbilical cord-derived mesenchymal stem cells http://dbarchive.biosciencedbc.jp/kyushu-u/hg19.../assembled/NoD.CDV.50.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells.bed ...

  6. File list: ALL.CDV.20.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.CDV.20.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells hg19 All antigens Ca...biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.CDV.20.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells.bed ... ...rdiovascular Umbilical cord-derived mesenchymal stem cells SRX831249,SRX831250,SRX831253,SRX831252,SRX831247

  7. File list: Unc.CDV.05.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.CDV.05.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells hg19 Unclassified Ca...ssembled/Unc.CDV.05.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells.bed ... ...rdiovascular Umbilical cord-derived mesenchymal stem cells http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/a

  8. File list: InP.CDV.20.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.CDV.20.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells hg19 Input control C...bc.jp/kyushu-u/hg19/assembled/InP.CDV.20.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells.bed ... ...ardiovascular Umbilical cord-derived mesenchymal stem cells SRX831247,SRX831246 http://dbarchive.bioscienced

  9. File list: NoD.CDV.05.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.CDV.05.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells hg19 No description ...Cardiovascular Umbilical cord-derived mesenchymal stem cells http://dbarchive.biosciencedbc.jp/kyushu-u/hg19.../assembled/NoD.CDV.05.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells.bed ...

  10. File list: Pol.CDV.50.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.CDV.50.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells hg19 RNA polymerase ...Cardiovascular Umbilical cord-derived mesenchymal stem cells http://dbarchive.biosciencedbc.jp/kyushu-u/hg19.../assembled/Pol.CDV.50.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells.bed ...

  11. File list: NoD.CDV.20.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.CDV.20.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells hg19 No description ...Cardiovascular Umbilical cord-derived mesenchymal stem cells http://dbarchive.biosciencedbc.jp/kyushu-u/hg19.../assembled/NoD.CDV.20.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells.bed ...

  12. File list: DNS.CDV.05.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.CDV.05.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells hg19 DNase-seq Cardiovascular Umbilical cord...-derived mesenchymal stem cells http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/DNS.CDV.05.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells.bed ...

  13. File list: Unc.CDV.20.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.CDV.20.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells hg19 Unclassified Ca...ssembled/Unc.CDV.20.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells.bed ... ...rdiovascular Umbilical cord-derived mesenchymal stem cells http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/a

  14. File list: ALL.CDV.10.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.CDV.10.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells hg19 All antigens Ca...biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.CDV.10.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells.bed ... ...rdiovascular Umbilical cord-derived mesenchymal stem cells SRX831253,SRX831250,SRX831249,SRX831252,SRX831247

  15. File list: Oth.CDV.50.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.CDV.50.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells hg19 TFs and others ...Cardiovascular Umbilical cord-derived mesenchymal stem cells http://dbarchive.biosciencedbc.jp/kyushu-u/hg19.../assembled/Oth.CDV.50.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells.bed ...

  16. File list: ALL.CDV.50.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.CDV.50.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells hg19 All antigens Ca...biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.CDV.50.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells.bed ... ...rdiovascular Umbilical cord-derived mesenchymal stem cells SRX831250,SRX831253,SRX831254,SRX831248,SRX831252

  17. File list: Pol.CDV.20.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.CDV.20.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells hg19 RNA polymerase ...Cardiovascular Umbilical cord-derived mesenchymal stem cells http://dbarchive.biosciencedbc.jp/kyushu-u/hg19.../assembled/Pol.CDV.20.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells.bed ...

  18. File list: NoD.CDV.10.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.CDV.10.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells hg19 No description ...Cardiovascular Umbilical cord-derived mesenchymal stem cells http://dbarchive.biosciencedbc.jp/kyushu-u/hg19.../assembled/NoD.CDV.10.AllAg.Umbilical_cord-derived_mesenchymal_stem_cells.bed ...

  19. Gingiva as a new and the most accessible source of mesenchymal stem cells from the oral cavity to be used in regenerative therapies

    Directory of Open Access Journals (Sweden)

    Bartłomiej Górski

    2016-08-01

    Full Text Available Since the discovery of bone marrow mesenchymal stem cells (BMMSCs, many researchers have focused their attention on new sources of mesenchymal stem cells (MSCs. Consequently, MSCs that display self-renewal capacity, multidifferentiation potential and immunomodulatory properties have been isolated from human oral tissues, including tooth, periodontal ligament, and gingiva. Oral MSCs involve dental pulp stem cells (DPSCs, stem cells from exfoliated deciduous teeth (SHED, periodontal ligament stem cells (PDLSCs, dental follicle stem cells (DFCs, stem cells from apical papilla (SCAP and gingival stem cells (GMSCs. Current research on oral stem cells is expanding at an unprecedented rate. That being the case, a plethora of in vitro differentiation assays, immunodeficient animal transplantations and preclinical trials have demonstrated that these cells exhibit strong potential for both regenerative dentistry and medicine. Oral MSCs have proved their capability to repair cornea, dental pulp, periodontal, bone, cartilage, tendon, neural, muscle and endothelial tissues without neoplasm formation as well as to treat inflammatory diseases and immune disorders. This article describes the current understanding of oral MSCs and their prospective applications in cell-based therapy, tissue engineering and regenerative medicine. Special attention is placed on GMSCs as they are easily accessible and may be obtained in a convenient and minimally invasive way.

  20. Molecular and environmental cues in cardiac differentiation of mesenchymal stem cells

    NARCIS (Netherlands)

    Ramkisoensing, Arti Anushka

    2014-01-01

    In this thesis molecular and environmental cues in cardiac differentiation of mesenchymal stem cells were investigated. The main conclusions were that the cardiac differentiation potential of human mesenchymal stem cells negatively correlates with donor age. This in its own shows a negative

  1. Mesenchymal Bone Morphogenetic Protein Signaling Is Required for Normal Pancreas Development

    Science.gov (United States)

    Ahnfelt-Rønne, Jonas; Ravassard, Philippe; Pardanaud-Glavieux, Corinne; Scharfmann, Raphaél; Serup, Palle

    2010-01-01

    OBJECTIVE Pancreas organogenesis is orchestrated by interactions between the epithelium and the mesenchyme, but these interactions are not completely understood. Here we investigated a role for bone morphogenetic protein (BMP) signaling within the pancreas mesenchyme and found it to be required for the normal development of the mesenchyme as well as for the pancreatic epithelium. RESEARCH DESIGN AND METHODS We analyzed active BMP signaling by immunostaining for phospho-Smad1,5,8 and tested whether pancreas development was affected by BMP inhibition after expression of Noggin and dominant negative BMP receptors in chicken and mouse pancreas. RESULTS Endogenous BMP signaling is confined to the mesenchyme in the early pancreas and inhibition of BMP signaling results in severe pancreatic hypoplasia with reduced epithelial branching. Notably, we also observed an excessive endocrine differentiation when mesenchymal BMP signaling is blocked, presumably secondary to defective mesenchyme to epithelium signaling. CONCLUSIONS We conclude that BMP signaling plays a previously unsuspected role in the mesenchyme, required for normal development of the mesenchyme as well as for the epithelium. PMID:20522595

  2. Epithelial-Mesenchymal Transition (EMT) Gene Variants and Epithelial Ovarian Cancer (EOC) Risk

    DEFF Research Database (Denmark)

    Amankwah, Ernest K.; Lin, Hui-Yi; Tyrer, Jonathan P.

    2015-01-01

    Epithelial-mesenchymal transition (EMT) is a process whereby epithelial cells assume mesenchymal characteristics to facilitate cancer metastasis. However, EMT also contributes to the initiation and development of primary tumors. Prior studies that explored the hypothesis that EMT gene variants co...

  3. Endothelial-Mesenchymal Transition : miR-101 as a new target to treat intimal hyperplasia

    NARCIS (Netherlands)

    Vanchin, B.; Maleszewska, M.; Kiers, B.; Brouwer, L. A.; Van Der Pol, B.; Pereira, A. C.; Harmsen, M. C.; Moonen, J. R. A. J.; Krenning, G.

    2016-01-01

    Introduction: Endothelial-Mesenchymal Transition (EndMT) is a specific form of endothelial dysfunction wherein endothelial cells acquire a mesenchymal phenotype and lose their endothelial functions. We, and others, recently described that EndMT contributes to intimal hyperplasia and atherosclerosis.

  4. Mesenchymal fibroblast growth factor receptor signaling regulates palatal shelf elevation during secondary palate formation

    Science.gov (United States)

    Yu, Kai; Karuppaiah, Kannan; Ornitz, David M.

    2015-01-01

    Palatal shelf elevation is an essential morphogenetic process during secondary palate closure and failure or delay of palatal shelf elevation is a common cause of cleft palate, one of the most common birth defects in humans. Here, we studied the role of mesenchymal fibroblast growth factor receptor (FGFR) signaling during palate development by conditional inactivation of Fgfrs using a mesenchyme-specific Dermo1-Cre driver. We showed that Fgfr1 is expressed throughout the palatal mesenchyme and Fgfr2 is expressed in the medial aspect of the posterior palatal mesenchyme overlapping with Fgfr1. Mesenchyme-specific disruption of Fgfr1 and Fgfr2 affected palatal shelf elevation and resulted in cleft palate. We further showed that both Fgfr1 and Fgfr2 are expressed in mesenchymal tissues of the mandibular process but display distinct expression patterns. Loss of mesenchymal FGFR signaling reduced mandibular ossification and lower jaw growth resulting in abnormal tongue insertion in the oral-nasal cavity. We propose a model to explain how redundant Fgfr1 and Fgfr2 expression in the palatal and mandibular mesenchyme regulates shelf medial wall protrusion and growth of the mandible to coordinate the craniofacial tissue movements that are required for palatal shelf elevation. PMID:26250517

  5. Design and development of a magnetic device for mesenchymal stem cell retaining in deep targets

    Science.gov (United States)

    Banis, G. C.

    2017-12-01

    This paper focuses on the retaining of mesenchymal stem cells in blood flow conditions using the appropriate magnetic field. Mesenchymal stem cells can be tagged with magnetic nanoparticles and thus, they can be manipulated from distance, through the application of an external magnetic field. In this paper the case of kidney as target of the therapy is being studied.

  6. Feasibility of intraperitoneal placental-derived mesenchymal stem cell injection in stomachs of diabetic mice.

    Science.gov (United States)

    Park, Jong Min; Lee, Sang Hwan; Kim, Kwang Il; Kim, Won Hee; Cho, Joo Young; Hahm, Ki Baik; Hong, Sung Pyo

    2017-11-15

    Diabetic gastropathy is associated with loss of interstitial cells of Cajal and autonomic neuropathy. Effective management for diabetic gastropathy is still unavailable. This study was aimed to confirm the pathogenetic changes in diabetic gastropathy and to examine the effect of treatment with placental-derived mesenchymal stem cells (PDMSCs) in stomachs of animal models. Fourteen non-obese diabetic/ShiLtJ mice of 8 weeks were bled until week 30. Diabetes mellitus developed in 10 out of 14 mice, which all survived with insulin. The mice were grouped into three groups: nondiabetic group (n = 4), diabetic sham group (n = 5), and diabetic PDMSC group (n = 5) all of which were treated with intraperitoneal PDMSCs injection at week 30. All mice were killed at week 34, and the stomachs were examined by immunohistochemical stain with c-kit and neuronal nitric oxide synthase antibodies. The number of c-kit positive cells in stomach decreased significantly in the diabetic sham group compared with that in the nondiabetic group (21.2 ± 6.7 vs 88.0 ± 29.3, P = 0.006) but increased with PDMSC treatment (21.2 ± 6.7 vs 64.0 ± 15.1, P = 0.02). The positive rate of neuronal nitric oxide synthase in neural plexus was also significantly lower in the diabetic sham group than in the nondiabetic group (22.3% ± 18.5% vs 48.0% ± 22.7%, P = 0.003) but increased with PDMSC treatment (22.3% ± 18.5% vs 43.3% ± 20.5%, P = 0.03). Interstitial cells of Cajal and neural plexus decreased in stomachs of mice with diabetes mellitus but were significantly repaired with intraperitoneal injection of PDMSC. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  7. Epidemiology of neural tube defects

    National Research Council Canada - National Science Library

    Seidahmed, Mohammed Z; Abdelbasit, Omar B; Shaheed, Meeralebbae M; Alhussein, Khalid A; Miqdad, Abeer M; Khalil, Mohamed I; Al-Enazy, Naif M; Salih, Mustafa A

    2014-01-01

    To find the prevalence of neural tube defects (NTDs), and compare the findings with local and international data, and highlight the important role of folic acid supplementation and flour fortification with folic acid in preventing NTDs...

  8. Neural Networks in Control Applications

    DEFF Research Database (Denmark)

    Sørensen, O.

    The intention of this report is to make a systematic examination of the possibilities of applying neural networks in those technical areas, which are familiar to a control engineer. In other words, the potential of neural networks in control applications is given higher priority than a detailed...... study of the networks themselves. With this end in view the following restrictions have been made: - Amongst numerous neural network structures, only the Multi Layer Perceptron (a feed-forward network) is applied. - Amongst numerous training algorithms, only four algorithms are examined, all...... in a recursive form (sample updating). The simplest is the Back Probagation Error Algorithm, and the most complex is the recursive Prediction Error Method using a Gauss-Newton search direction. - Over-fitting is often considered to be a serious problem when training neural networks. This problem is specifically...

  9. Memristor-based neural networks

    Science.gov (United States)

    Thomas, Andy

    2013-03-01

    The synapse is a crucial element in biological neural networks, but a simple electronic equivalent has been absent. This complicates the development of hardware that imitates biological architectures in the nervous system. Now, the recent progress in the experimental realization of memristive devices has renewed interest in artificial neural networks. The resistance of a memristive system depends on its past states and exactly this functionality can be used to mimic the synaptic connections in a (human) brain. After a short introduction to memristors, we present and explain the relevant mechanisms in a biological neural network, such as long-term potentiation and spike time-dependent plasticity, and determine the minimal requirements for an artificial neural network. We review the implementations of these processes using basic electric circuits and more complex mechanisms that either imitate biological systems or could act as a model system for them.

  10. Neural Networks in Control Applications

    DEFF Research Database (Denmark)

    Sørensen, O.

    simulated process and compared. The closing chapter describes some practical experiments, where the different control concepts and training methods are tested on the same practical process operating in very noisy environments. All tests confirm that neural networks also have the potential to be trained......The intention of this report is to make a systematic examination of the possibilities of applying neural networks in those technical areas, which are familiar to a control engineer. In other words, the potential of neural networks in control applications is given higher priority than a detailed...... study of the networks themselves. With this end in view the following restrictions have been made: - Amongst numerous neural network structures, only the Multi Layer Perceptron (a feed-forward network) is applied. - Amongst numerous training algorithms, only four algorithms are examined, all...

  11. Neural components of altruistic punishment

    Directory of Open Access Journals (Sweden)

    Emily eDu

    2015-02-01

    Full Text Available Altruistic punishment, which occurs when an individual incurs a cost to punish in response to unfairness or a norm violation, may play a role in perpetuating cooperation. The neural correlates underlying costly punishment have only recently begun to be explored. Here we review the current state of research on the neural basis of altruism from the perspectives of costly punishment, emphasizing the importance of characterizing elementary neural processes underlying a decision to punish. In particular, we emphasize three cognitive processes that contribute to the decision to altruistically punish in most scenarios: inequity aversion, cost-benefit calculation, and social reference frame to distinguish self from others. Overall, we argue for the importance of understanding the neural correlates of altruistic punishment with respect to the core computations necessary to achieve a decision to punish.

  12. Complex-Valued Neural Networks

    CERN Document Server

    Hirose, Akira

    2012-01-01

    This book is the second enlarged and revised edition of the first successful monograph on complex-valued neural networks (CVNNs) published in 2006, which lends itself to graduate and undergraduate courses in electrical engineering, informatics, control engineering, mechanics, robotics, bioengineering, and other relevant fields. In the second edition the recent trends in CVNNs research are included, resulting in e.g. almost a doubled number of references. The parametron invented in 1954 is also referred to with discussion on analogy and disparity. Also various additional arguments on the advantages of the complex-valued neural networks enhancing the difference to real-valued neural networks are given in various sections. The book is useful for those beginning their studies, for instance, in adaptive signal processing for highly functional sensing and imaging, control in unknown and changing environment, robotics inspired by human neural systems, and brain-like information processing, as well as interdisciplina...

  13. Neural components of altruistic punishment.

    Science.gov (United States)

    Du, Emily; Chang, Steve W C

    2015-01-01

    Altruistic punishment, which occurs when an individual incurs a cost to punish in response to unfairness or a norm violation, may play a role in perpetuating cooperation. The neural correlates underlying costly punishment have only recently begun to be explored. Here we review the current state of research on the neural basis of altruism from the perspectives of costly punishment, emphasizing the importance of characterizing elementary neural processes underlying a decision to punish. In particular, we emphasize three cognitive processes that contribute to the decision to altruistically punish in most scenarios: inequity aversion, cost-benefit calculation, and social reference frame to distinguish self from others. Overall, we argue for the importance of understanding the neural correlates of altruistic punishment with respect to the core computations necessary to achieve a decision to punish.

  14. Pansharpening by Convolutional Neural Networks

    National Research Council Canada - National Science Library

    Masi, Giuseppe; Cozzolino, Davide; Verdoliva, Luisa; Scarpa, Giuseppe

    2016-01-01

    A new pansharpening method is proposed, based on convolutional neural networks. We adapt a simple and effective three-layer architecture recently proposed for super-resolution to the pansharpening problem...

  15. L-carnitine contributes to enhancement of neurogenesis from mesenchymal stem cells through Wnt/β-catenin and PKA pathway.

    Science.gov (United States)

    Fathi, Ezzatollah; Farahzadi, Raheleh; Charoudeh, Hojjatollah Nozad

    2017-03-01

    The identification of factors capable of enhancing neurogenesis has great potential for cellular therapies in neurodegenerative diseases. Multiple studies have shown the neuroprotective effects of L-carnitine (LC). This study determined whether neuronal differentiation of rat adipose tissue-derived mesenchymal stem cells (ADSCs) can be activated by LC. In this study, protein kinase A (PKA) and Wnt/β-catenin pathways were detected to show if this activation was due to these pathways. The expression of LC-induced neurogenesis markers in ADSCs was characterized using real-time PCR. ELISA was conducted to assess the expression of cyclic adenosine monophosphate (cAMP) and PKA. The expression of β-catenin, reduced dickkopf1 (DKK1), low-density lipoprotein receptor-related protein 5 (LRP5), Wnt1, and Wnt3a genes as Wnt/β-catenin signaling members were used to detect the Wnt/β-catenin pathway. It was observed that LC could promote neurogenesis in ADSCs as well as expression of some neurogenic markers. Moreover, LC causes to increase the cAMP levels and PKA activity. Treatment of ADSCs with H-89 (dihydrochloride hydrate) as PKA inhibitor significantly inhibited the promotion of neurogenic markers, indicating that the PKA signaling pathway could be involved in neurogenesis induction. Analyses of real-time PCR data showed that the mRNA expressions of β-catenin, DKK1, LRP5c-myc, Wnt1, and Wnt3a were increased in the presence of LC. Therefore, the present study showed that LC promotes ADSCs neurogenesis and the LC-induced neurogenic markers could be due to both the PKA and Wnt/β-catenin signaling pathway. Impact statement Neural tissue has long been believed as incapable of regeneration and the identification of cell types and factors capable of neuronal differentiation has generated intense interest. Mesenchymal stem cells (MSCs) are considered as potential targets for stem cell-based therapy. L-carnitin (LC) as an antioxidant may have neuroprotective effects in

  16. What are artificial neural networks?

    DEFF Research Database (Denmark)

    Krogh, Anders

    2008-01-01

    Artificial neural networks have been applied to problems ranging from speech recognition to prediction of protein secondary structure, classification of cancers and gene prediction. How do they work and what might they be good for? Udgivelsesdato: 2008-Feb......Artificial neural networks have been applied to problems ranging from speech recognition to prediction of protein secondary structure, classification of cancers and gene prediction. How do they work and what might they be good for? Udgivelsesdato: 2008-Feb...

  17. Indices for Testing Neural Codes

    OpenAIRE

    Jonathan D. Victor; Nirenberg, Sheila

    2008-01-01

    One of the most critical challenges in systems neuroscience is determining the neural code. A principled framework for addressing this can be found in information theory. With this approach, one can determine whether a proposed code can account for the stimulus-response relationship. Specifically, one can compare the transmitted information between the stimulus and the hypothesized neural code with the transmitted information between the stimulus and the behavioral response. If the former is ...

  18. Biologically Inspired Modular Neural Networks

    OpenAIRE

    Azam, Farooq

    2000-01-01

    This dissertation explores the modular learning in artificial neural networks that mainly driven by the inspiration from the neurobiological basis of the human learning. The presented modularization approaches to the neural network design and learning are inspired by the engineering, complexity, psychological and neurobiological aspects. The main theme of this dissertation is to explore the organization and functioning of the brain to discover new structural and learning ...

  19. Differences in neural crest sensitivity to ethanol account for the infrequency of anterior segment defects in the eye compared with craniofacial anomalies in a zebrafish model of fetal alcohol syndrome.

    Science.gov (United States)

    Eason, Jessica; Williams, Antionette L; Chawla, Bahaar; Apsey, Christian; Bohnsack, Brenda L

    2017-09-01

    Ethanol (ETOH) exposure during pregnancy is associated with craniofacial and neurologic abnormalities, but infrequently disrupts the anterior segment of the eye. In these studies, we used zebrafish to investigate differences in the teratogenic effect of ETOH on craniofacial, periocular, and ocular neural crest. Zebrafish eye and neural crest development was analyzed by means of live imaging, TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) assay, immunostaining, detection of reactive oxygen species, and in situ hybridization. Our studies demonstrated that foxd3-positive neural crest cells in the periocular mesenchyme and developing eye were less sensitive to ETOH than sox10-positive craniofacial neural crest cells that form the pharyngeal arches and jaw. ETOH increased apoptosis in the retina, but did not affect survival of periocular and ocular neural crest cells. ETOH also did not increase reactive oxygen species within the eye. In contrast, ETOH increased ventral neural crest apoptosis and reactive oxygen species production in the facial mesenchyme. In the eye and craniofacial region, sod2 showed high levels of expression in the anterior segment and in the setting of Sod2 knockdown, low levels of ETOH decreased migration of foxd3-positive neural crest cells into the developing eye. However, ETOH had minimal effect on the periocular and ocular expression of transcription factors (pitx2 and foxc1) that regulate anterior segment development. Neural crest cells contributing to the anterior segment of the eye exhibit increased ability to withstand ETOH-induced oxidative stress and apoptosis. These studies explain the rarity of anterior segment dysgenesis despite the frequent craniofacial abnormalities in fetal alcohol syndrome. Birth Defects Research 109:1212-1227, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  20. Circulating tumour cells lacking cytokeratin in breast cancer: the importance of being mesenchymal

    Science.gov (United States)

    Gradilone, Angela; Raimondi, Cristina; Nicolazzo, Chiara; Petracca, Arianna; Gandini, Orietta; Vincenzi, Bruno; Naso, Giuseppe; Aglianò, Anna Maria; Cortesi, Enrico; Gazzaniga, Paola

    2011-01-01

    Abstract Circulating tumour cells (CTCs) are independent predictor of prognosis in metastatic breast cancer. Nevertheless, in one third of patients, circulating tumour cells are undetected by conventional methods. Aim of the study was to assess the prognostic value of circulating tumour cells expressing mesenchymal markers in metastatic breast cancer patients. We isolated CTC from blood of 55 metastatic breast cancer patients. CTC were characterized for cytokeratins and markers of epithelial mesenchymal transition. The gain of mesenchymal markers in CTC was correlated to prognosis of patients in a follow-up of 24 months. The presence of mesenchymal markers on CTC more accurately predicted worse prognosis than the expression of cytokeratins alone. Because of the frequent loss of epithelial antigens by CTC, assays targeting epithelial antigens may miss the most invasive cell population. Thus, there is an urgent need to improve detection methods to identify CTC which undergone epithelial mesenchymal transition program. PMID:21352474

  1. The role of Wt1 in regulating mesenchyme in cancer, development, and tissue homeostasis.

    Science.gov (United States)

    Chau, You-Ying; Hastie, Nicholas D

    2012-10-01

    From both the fundamental and clinical perspectives, there is growing interest in mesenchymal cells and the mechanisms that regulate the two-way switch between mesenchymal and epithelial states. Here, we review recent findings showing that the Wilms' tumor gene (Wt1) is a key regulator of mesenchyme maintenance and the mesenchyme to epithelial balance in the development of certain mesodermal organs. We summarize recent experiments demonstrating, unexpectedly, that Wt1 is also essential for the integrity or function of multiple adult tissues, mainly, we argue, through regulating mesenchymal cells. We also discuss growing evidence that implicates Wt1 in tissue repair and regeneration. Drawing on these findings, we highlight the similarities between Wt1-expressing cells in different tissues. We believe that future studies aimed at elucidating the mechanisms underlying the functions of Wt1 in adult cells will reveal key cell types, pathways, and molecules regulating adult tissue homeostasis and repair. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. Propofol promotes spinal cord injury repair by bone marrow mesenchymal stem cell transplantation.

    Science.gov (United States)

    Zhou, Ya-Jing; Liu, Jian-Min; Wei, Shu-Ming; Zhang, Yun-Hao; Qu, Zhen-Hua; Chen, Shu-Bo

    2015-08-01

    Propofol is a neuroprotective anesthetic. Whether propofol can promote spinal cord injury repair by bone marrow mesenchymal stem cells remains poorly understood. We used rats to investigate spinal cord injury repair using bone marrow mesenchymal stem cell transplantation combined with propofol administration via the tail vein. Rat spinal cord injury was clearly alleviated; a large number of newborn non-myelinated and myelinated nerve fibers appeared in the spinal cord, the numbers of CM-Dil-labeled bone marrow mesenchymal stem cells and fluorogold-labeled nerve fibers were increased and hindlimb motor function of spinal cord-injured rats was markedly improved. These improvements were more prominent in rats subjected to bone marrow mesenchymal cell transplantation combined with propofol administration than in rats receiving monotherapy. These results indicate that propofol can enhance the therapeutic effects of bone marrow mesenchymal stem cell transplantation on spinal cord injury in rats.

  3. Propofol promotes spinal cord injury repair by bone marrow mesenchymal stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Ya-jing Zhou

    2015-01-01

    Full Text Available Propofol is a neuroprotective anesthetic. Whether propofol can promote spinal cord injury repair by bone marrow mesenchymal stem cells remains poorly understood. We used rats to investigate spinal cord injury repair using bone marrow mesenchymal stem cell transplantation combined with propofol administration via the tail vein. Rat spinal cord injury was clearly alleviated; a large number of newborn non-myelinated and myelinated nerve fibers appeared in the spinal cord, the numbers of CM-Dil-labeled bone marrow mesenchymal stem cells and fluorogold-labeled nerve fibers were increased and hindlimb motor function of spinal cord-injured rats was markedly improved. These improvements were more prominent in rats subjected to bone marrow mesenchymal cell transplantation combined with propofol administration than in rats receiving monotherapy. These results indicate that propofol can enhance the therapeutic effects of bone marrow mesenchymal stem cell transplantation on spinal cord injury in rats.

  4. Neural-like growing networks

    Science.gov (United States)

    Yashchenko, Vitaliy A.

    2000-03-01

    On the basis of the analysis of scientific ideas reflecting the law in the structure and functioning the biological structures of a brain, and analysis and synthesis of knowledge, developed by various directions in Computer Science, also there were developed the bases of the theory of a new class neural-like growing networks, not having the analogue in world practice. In a base of neural-like growing networks the synthesis of knowledge developed by classical theories - semantic and neural of networks is. The first of them enable to form sense, as objects and connections between them in accordance with construction of the network. With thus each sense gets a separate a component of a network as top, connected to other tops. In common it quite corresponds to structure reflected in a brain, where each obvious concept is presented by certain structure and has designating symbol. Secondly, this network gets increased semantic clearness at the expense owing to formation not only connections between neural by elements, but also themselves of elements as such, i.e. here has a place not simply construction of a network by accommodation sense structures in environment neural of elements, and purely creation of most this environment, as of an equivalent of environment of memory. Thus neural-like growing networks are represented by the convenient apparatus for modeling of mechanisms of teleological thinking, as a fulfillment of certain psychophysiological of functions.

  5. Flexibility of neural stem cells

    Directory of Open Access Journals (Sweden)

    Eumorphia eRemboutsika

    2011-04-01

    Full Text Available Embryonic cortical neural stem cells are self-renewing progenitors that can differentiate into neurons and glia. We generated neurospheres from the developing cerebral cortex using a mouse genetic model that allows for lineage selection and found that the self-renewing neural stem cells are restricted to Sox2 expressing cells. Under normal conditions, embryonic cortical neurospheres are heterogeneous with regard to Sox2 expression and contain astrocytes, neural stem cells and neural progenitor cells sufficiently plastic to give rise to neural crest cells when transplanted into the hindbrain of E1.5 chick and E8 mouse embryos. However, when neurospheres are maintained under lineage selection, such that all cells express Sox2, neural stem cells maintain their Pax6+ cortical radial glia identity and exhibit a more restricted fate in vitro and after transplantation. These data demonstrate that Sox2 preserves the cortical identity and regulates the plasticity of self-renewing Pax6+ radial glia cells.

  6. Spiking modular neural networks: A neural network modeling approach for hydrological processes

    National Research Council Canada - National Science Library

    Kamban Parasuraman; Amin Elshorbagy; Sean K. Carey

    2006-01-01

    .... In this study, a novel neural network model called the spiking modular neural networks (SMNNs) is proposed. An SMNN consists of an input layer, a spiking layer, and an associator neural network layer...

  7. Immunosuppressive and remodelling properties of mesenchymal stem cells in a model of chronic kidney disease

    Directory of Open Access Journals (Sweden)

    Patricia Semedo

    2009-12-01

    Full Text Available Objective: To investigate the role of mesenchymal stem cells in fibrogenesis using a model of chronic renal insufficiency. Methods: Mesenchymal stem cells  were obtained from tibias and femurs of Wistar-EPM rats. After three to five passages, the cells were submitted to phenotypic analyses and differentiation. Wistar rats were submitted to the 5/6 nephrectomy model, and 2.105 mesenchymal stem cells  were administered intravenously to each rat every two weeks until the eighth week. Rresults: Sex-determining region Y was observed in female rats treated with stem cells. Serum and urine analyses showed improvement of functional parameters in mesenchymal stem cells treated animals, such as creatinine, serum urea, and proteinuria. Moreover, hemocrit analysis showed improvement of anemia in mesenchymal stem cells treated animals. Masson’s Trichromium and Picrosirius Red staining demonstrated reduced levels of fibrosis in mesenchymal stem cells treated in animals. These results were corroborated by reduced vimentin, collagen I, TGFβ, FSP-1, MCP-1 and Smad3 mRNA expression. Renal IL-6 and TNFα mRNA expression levels were significantly decreased after mesenchymal stem cells treatment, while IL-4 and IL-10 expression were increased. Serum expression of IL-1α, IL-1β, IL-6, IFN-γ, TNF-α, and IL-10 was decreased in mesenchymal cell-treated animals. Cconclusions: Altogether, these results suggest that mesenchymal stem cells therapy can indeed modulate the inflammatory response that follows the initial phase of a chronic renal lesion. The immunosuppresive and remodeling properties of the mesenchymal stem cells  may be involved in the improved fibrotic outcome.

  8. Systems biology of facial development: contributions of ectoderm and mesenchyme.

    Science.gov (United States)

    Hooper, Joan E; Feng, Weiguo; Li, Hong; Leach, Sonia M; Phang, Tzulip; Siska, Charlotte; Jones, Kenneth L; Spritz, Richard A; Hunter, Lawrence E; Williams, Trevor

    2017-06-01

    The rapid increase in gene-centric biological knowledge coupled with analytic approaches for genomewide data integration provides an opportunity to develop systems-level understanding of facial development. Experimental analyses have demonstrated the importance of signaling between the surface ectoderm and the underlying mesenchyme are coordinating facial patterning. However, current transcriptome data from the developing vertebrate face is dominated by the mesenchymal component, and the contributions of the ectoderm are not easily identified. We have generated transcriptome datasets from critical periods of mouse face formation that enable gene expression to be analyzed with respect to time, prominence, and tissue layer. Notably, by separating the ectoderm and mesenchyme we considerably improved the sensitivity compared to data obtained from whole prominences, with more genes detected over a wider dynamic range. From these data we generated a detailed description of ectoderm-specific developmental programs, including pan-ectodermal programs, prominence- specific programs and their temporal dynamics. The genes and pathways represented in these programs provide mechanistic insights into several aspects of ectodermal development. We also used these data to identify co-expression modules specific to facial development. We then used 14 co-expression modules enriched for genes involved in orofacial clefts to make specific mechanistic predictions about genes involved in tongue specification, in nasal process patterning and in jaw development. Our multidimensional gene expression dataset is a unique resource for systems analysis of the developing face; our co-expression modules are a resource for predicting functions of poorly annotated genes, or for predicting roles for genes that have yet to be studied in the context of facial development; and our analytic approaches provide a paradigm for analysis of other complex developmental programs. Copyright © 2017 Elsevier Inc

  9. Mesenchymal Dental Pulp Cells Attenuate Dentin Resorption in Homeostasis

    Science.gov (United States)

    Zheng, Y.; Chen, M.; He, L.; Marão, H.F.; Sun, D.M.; Zhou, J.; Kim, S.G.; Song, S.; Wang, S.L.

    2015-01-01

    Dentin in permanent teeth rarely undergoes resorption in development, homeostasis, or aging, in contrast to bone that undergoes periodic resorption/remodeling. The authors hypothesized that cells in the mesenchymal compartment of dental pulp attenuate osteoclastogenesis. Mononucleated and adherent cells from donor-matched rat dental pulp (dental pulp cells [DPCs]) and alveolar bone (alveolar bone cells [ABCs]) were isolated and separately cocultured with primary rat splenocytes. Primary splenocytes readily aggregated and formed osteoclast-like cells in chemically defined osteoclastogenesis medium with 20 ng/mL of macrophage colony-stimulating factor (M-CSF) and 50 ng/mL of receptor activator of nuclear factor κB ligand (RANKL). Strikingly, DPCs attenuated osteoclastogenesis when cocultured with primary splenocytes, whereas ABCs slightly but significantly promoted osteoclastogenesis. DPCs yielded ~20-fold lower RANKL expression but >2-fold higher osteoprotegerin (OPG) expression than donor-matched ABCs, yielding a RANKL/OPG ratio of 41:1 (ABCs:DPCs). Vitamin D3 significantly promoted RANKL expression in ABCs and OPG in DPCs. In vivo, rat maxillary incisors were atraumatically extracted (without any tooth fractures), followed by retrograde pulpectomy to remove DPCs and immediate replantation into the extraction sockets to allow repopulation of the surgically treated root canal with periodontal and alveolar bone–derived cells. After 8 wk, multiple dentin/root resorption lacunae were present in root dentin with robust RANKL and OPG expression. There were areas of dentin resoprtion alternating with areas of osteodentin formation in root dentin surface in the observed 8 wk. These findings suggest that DPCs of the mesenchymal compartment have an innate ability to attenuate osteoclastogenesis and that this innate ability may be responsible for the absence of dentin resorption in homeostasis. Mesenchymal attenuation of dentin resorption may have implications in internal

  10. Mesenchymal dental pulp cells attenuate dentin resorption in homeostasis.

    Science.gov (United States)

    Zheng, Y; Chen, M; He, L; Marão, H F; Sun, D M; Zhou, J; Kim, S G; Song, S; Wang, S L; Mao, J J

    2015-06-01

    Dentin in permanent teeth rarely undergoes resorption in development, homeostasis, or aging, in contrast to bone that undergoes periodic resorption/remodeling. The authors hypothesized that cells in the mesenchymal compartment of dental pulp attenuate osteoclastogenesis. Mononucleated and adherent cells from donor-matched rat dental pulp (dental pulp cells [DPCs]) and alveolar bone (alveolar bone cells [ABCs]) were isolated and separately cocultured with primary rat splenocytes. Primary splenocytes readily aggregated and formed osteoclast-like cells in chemically defined osteoclastogenesis medium with 20 ng/mL of macrophage colony-stimulating factor (M-CSF) and 50 ng/mL of receptor activator of nuclear factor κB ligand (RANKL). Strikingly, DPCs attenuated osteoclastogenesis when cocultured with primary splenocytes, whereas ABCs slightly but significantly promoted osteoclastogenesis. DPCs yielded ~20-fold lower RANKL expression but >2-fold higher osteoprotegerin (OPG) expression than donor-matched ABCs, yielding a RANKL/OPG ratio of 41:1 (ABCs:DPCs). Vitamin D3 significantly promoted RANKL expression in ABCs and OPG in DPCs. In vivo, rat maxillary incisors were atraumatically extracted (without any tooth fractures), followed by retrograde pulpectomy to remove DPCs and immediate replantation into the extraction sockets to allow repopulation of the surgically treated root canal with periodontal and alveolar bone-derived cells. After 8 wk, multiple dentin/root resorption lacunae were present in root dentin with robust RANKL and OPG expression. There were areas of dentin resoprtion alternating with areas of osteodentin formation in root dentin surface in the observed 8 wk. These findings suggest that DPCs of the mesenchymal compartment have an innate ability to attenuate osteoclastogenesis and that this innate ability may be responsible for the absence of dentin resorption in homeostasis. Mesenchymal attenuation of dentin resorption may have implications in internal

  11. Restoration of Mesenchymal RPE by Transcription Factor-Mediated Reprogramming.

    Science.gov (United States)

    Shih, Ying-Hsuan; Radeke, Monte J; Radeke, Carolyn M; Coffey, Pete J

    2017-01-01

    Transforming growth factor β-mediated epithelial-to-mesenchymal transition (EMT) is a major component of the wound healing response and a negative determinant of retinal pigment epithelium (RPE) differentiation. We have shown previously that inhibition of TGFβ signaling restored the capacity of mesenchymal RPE to differentiate; however, the potential lessens with extensive passaging. We investigated TGFβ-independent mechanisms that regulate RPE differentiation following repetitive passaging. Retinal pigment epithelium-EMT was induced by repetitive passaging of fetal RPE at subconfluence. Suppression of EMT was achieved by the addition of A-83-01, a TGFβ receptor kinase inhibitor. Transcriptomic analysis was used to identify potential TGFβ independent processes that prevent differentiation after extensive passage. Downregulated transcription factors were identified and transduced into highly passaged RPE to restore cell differentiation. Restoration was evaluated according to morphology, expression of RPE/mesenchymal markers, transcriptomic analysis, cell doubling time, and senescence-associated β-galactosidase (SA-β-gal) activity. A-83-01-treated RPE failed to differentiate after 7 passages (P7). This failure was concomitant with downregulation of RPE genes, misregulation of cell cycle genes, a decline in proliferative potential, and cell senescence. Exogenous expression of MYCN and OTX2 in conjunction with A-83-01 restored P7-RPE differentiation to a status similar to minimally passaged RPE. Moreover, the treatment allowed cells to maintain their differentiation capacity after extended passaging. Retinal pigment epithelium subjected to chronic wound stimulus undergoes TGFβ-mediated EMT, loss of expression of signature RPE genes, and senescence. Targeting these aspects with a TGFβ receptor kinase inhibitor, a RPE transcription factor, and a cell cycle regulator restores the capacity of highly passaged RPE cells to regenerate and differentiate.

  12. Influence of neural adaptation on dynamics and equilibrium state of neural activities in a ring neural network

    Science.gov (United States)

    Takiyama, Ken

    2017-12-01

    How neural adaptation affects neural information processing (i.e. the dynamics and equilibrium state of neural activities) is a central question in computational neuroscience. In my previous works, I analytically clarified the dynamics and equilibrium state of neural activities in a ring-type neural network model that is widely used to model the visual cortex, motor cortex, and several other brain regions. The neural dynamics and the equilibrium state in the neural network model corresponded to a Bayesian computation and statistically optimal multiple information integration, respectively, under a biologically inspired condition. These results were revealed in an analytically tractable manner; however, adaptation effects were not considered. Here, I analytically reveal how the dynamics and equilibrium state of neural activities in a ring neural network are influenced by spike-frequency adaptation (SFA). SFA is an adaptation that causes gradual inhibition of neural activity when a sustained stimulus is applied, and the strength of this inhibition depends on neural activities. I reveal that SFA plays three roles: (1) SFA amplifies the influence of external input in neural dynamics; (2) SFA allows the history of the external input to affect neural dynamics; and (3) the equilibrium state corresponds to the statistically optimal multiple information integration independent of the existence of SFA. In addition, the equilibrium state in a ring neural network model corresponds to the statistically optimal integration of multiple information sources under biologically inspired conditions, independent of the existence of SFA.

  13. Transition of mesenchymal stem/stromal cells to endothelial cells.

    Science.gov (United States)

    Crisan, Mihaela

    2013-08-14

    Mesenchymal stem/stromal cells (MSCs) are heterogeneous. A fraction of these cells constitute multipotent cells that can self-renew and mainly give rise to mesodermal lineage cells such as adipocytes, osteocytes and chondrocytes. The ability of MSCs to differentiate into endothelial cells remains controversial. Isolation and in vitro manipulation of MSCs before clinical application are important steps. High numbers of MSCs are needed, requiring the in vitro expansion of these clinically important cells. To this end, a well-controlled procedure for MSC isolation and maintenance in culture is necessary.

  14. Mesenchymal stem cells in diabetes treatment: progress and perspectives

    Directory of Open Access Journals (Sweden)

    Yu CHENG

    2016-08-01

    Full Text Available Diabetes is a chronic metabolic disorder caused by relative or absolute insulin deficient or reduced sensitivity of target cells to insulin. Mesenchymal stem cells (MSCs are adult stem cells with multiple differentiation potential, self-renewable and immunoregulatory properties. Accumulating evidences from clinic or animal experiments recent years showed that MSCs infusion could ameliorate hyperglycemia in diabetes. The research progress of MSCs in diabetes treatment is summarized and a corresponding perspective is herewith proposed in present paper. DOI: 10.11855/j.issn.0577-7402.2016.07.16

  15. Mesenchymal stem cell-mediated functional tooth regeneration in swine.

    Science.gov (United States)

    Sonoyama, Wataru; Liu, Yi; Fang, Dianji; Yamaza, Takayoshi; Seo, Byoung-Moo; Zhang, Chunmei; Liu, He; Gronthos, Stan; Wang, Cun-Yu; Wang, Songlin; Shi, Songtao

    2006-12-20

    Mesenchymal stem cell-mediated tissue regeneration is a promising approach for regenerative medicine for a wide range of applications. Here we report a new population of stem cells isolated from the root apical papilla of human teeth (SCAP, stem cells from apical papilla). Using a minipig model, we transplanted both human SCAP and periodontal ligament stem cells (PDLSCs) to generate a root/periodontal complex capable of supporting a porcelain crown, resulting in normal tooth function. This work integrates a stem cell-mediated tissue regeneration strategy, engineered materials for structure, and current dental crown technologies. This hybridized tissue engineering approach led to recovery of tooth strength and appearance.

  16. Mesenchymal stem cell-mediated functional tooth regeneration in swine.

    Directory of Open Access Journals (Sweden)

    Wataru Sonoyama

    2006-12-01

    Full Text Available Mesenchymal stem cell-mediated tissue regeneration is a promising approach for regenerative medicine for a wide range of applications. Here we report a new population of stem cells isolated from the root apical papilla of human teeth (SCAP, stem cells from apical papilla. Using a minipig model, we transplanted both human SCAP and periodontal ligament stem cells (PDLSCs to generate a root/periodontal complex capable of supporting a porcelain crown, resulting in normal tooth function. This work integrates a stem cell-mediated tissue regeneration strategy, engineered materials for structure, and current dental crown technologies. This hybridized tissue engineering approach led to recovery of tooth strength and appearance.

  17. Epithelial-mesenchymal transition: An emerging target in tissue fibrosis

    Science.gov (United States)

    Li, Meirong; Luan, Fuxin; Zhao, Yali; Hao, Haojie; Zhou, Yong; Han, Weidong

    2016-01-01

    Epithelial-mesenchymal transition (EMT) is involved in a variety of tissue fibroses. Fibroblasts/myofibroblasts derived from epithelial cells contribute to the excessive accumulation of fibrous connective tissue in damaged tissue, which can lead to permanent scarring or organ malfunction. Therefore, EMT-related fibrosis cannot be neglected. This review highlights the findings that demonstrate the EMT to be a direct contributor to the fibroblast/myofibroblast population in the development of tissue fibrosis and helps to elucidate EMT-related anti-fibrotic strategies, which may enable the development of therapeutic interventions to suppress EMT and potentially reverse organ fibrosis. PMID:26361988

  18. Mesenchymal stem cells as therapeutic delivery vehicles targeting tumor stroma

    DEFF Research Database (Denmark)

    Serakinci, Nedime; Christensen, Rikke; Sørensen, Flemming Brandt

    2011-01-01

    The field of stem cell biology continues to evolve by characterization of further types of stem cells and by exploring their therapeutic potential for experimental and clinical applications. Human mesenchymal stem cells (hMSCs) are one of the most promising candidates simply because...... better understanding and in vivo supporting data. The homing ability of hMSCs was investigated by creating a human xenograft model by transplanting an ovarian cancer cell line into immunocompromised mice. Then, genetically engineered hMSC-telo1 cells were injected through the tail vein...

  19. Tumourigenicity and radiation resistance of mesenchymal stem cells

    DEFF Research Database (Denmark)

    D'Andrea, Filippo Peder; Horsman, Michael Robert; Kassem, Moustapha

    2012-01-01

    Background. Cancer stem cells are believed to be more radiation resistant than differentiated tumour cells of the same origin. It is not known, however, whether normal nontransformed adult stem cells share the same radioresistance as their cancerous counterpart. Material and methods....... Nontumourigenic (TERT4) and tumourigenic (TRET20) cell lines, from an immortalised mesenchymal stem cell line, were grown in culture prior to irradiation and gene expression analysis. Radiation resistance was measured using a clonogenic assay. Differences in gene expression between the two cell lines, both under...... the intercellular matrix. These results also indicate that cancer stem cells are more radiation resistant than stem cells of the same origin....

  20. Importance of mesenchymal stem cells in autologous fat grafting

    DEFF Research Database (Denmark)

    Trojahn Kølle, Stig-Frederik; Oliveri, Roberto S; Glovinski, Peter Viktor

    2012-01-01

    the fat graft with adipose tissue-derived mesenchymal stem cells (ASC) before transplantation. We have reviewed original studies published on fat transplantation enriched with ASC. We found four murine and three human studies that investigated the subject after a sensitive search of publications....... In the human studies, so-called cell assisted lipotransfer (CAL) increased the ASC concentration 2-5 times compared with non-manipulated fat grafts, which caused a questionable improvement in survival of fat grafts, compared with that of traditional lipofilling. In contrast, in two of the murine studies ASC...

  1. Sarcomas as a mise en abyme of mesenchymal stem cells

    DEFF Research Database (Denmark)

    Burns, Jorge S.; Safwat, Akmal Ahmed; Grisendi, Giulia

    2012-01-01

    Mise en abyme meaning "placed into abyss or infinite recurrence" is an apt paradigm for the relentless growth of sarcoma cells. Its alternative meaning, "self-reflexive embedding" fits the central role attributed to cancer stem cells (CSCs). Diversely sourced and defined, mesenchymal stem cells...... (MSCs) may be the cells of sarcoma origin, evolve a CSC phenotype and/or contribute to tumor growth through inherent qualities for homing, neovascularization, paracrine cross-feeding, microvesicle secretion, cell fusion, entosis and immune modulation. Exploiting these qualities, MSC expressing modified...

  2. Stem cell property of postmigratory cranial neural crest cells and their utility in alveolar bone regeneration and tooth development.

    Science.gov (United States)

    Chung, Il-Hyuk; Yamaza, Takayoshi; Zhao, Hu; Choung, Pill-Hoon; Shi, Songtao; Chai, Yang

    2009-04-01

    The vertebrate neural crest is a multipotent cell population that gives rise to a variety of different cell types. We have discovered that postmigratory cranial neural crest cells (CNCCs) maintain mesenchymal stem cell characteristics and show potential utility for the regeneration of craniofacial structures. We are able to induce the osteogenic differentiation of postmigratory CNCCs, and this differentiation is regulated by bone morphogenetic protein (BMP) and transforming growth factor-beta signaling pathways. After transplantation into a host animal, postmigratory CNCCs form bone matrix. CNCC-formed bones are distinct from bones regenerated by bone marrow mesenchymal stem cells. In addition, CNCCs support tooth germ survival via BMP signaling in our CNCC-tooth germ cotransplantation system. Thus, we conclude that postmigratory CNCCs preserve stem cell features, contribute to craniofacial bone formation, and play a fundamental role in supporting tooth organ development. These findings reveal a novel function for postmigratory CNCCs in organ development, and demonstrate the utility of these CNCCs in regenerating craniofacial structures.

  3. Fractional Hopfield Neural Networks: Fractional Dynamic Associative Recurrent Neural Networks.

    Science.gov (United States)

    Pu, Yi-Fei; Yi, Zhang; Zhou, Ji-Liu

    2017-10-01

    This paper mainly discusses a novel conceptual framework: fractional Hopfield neural networks (FHNN). As is commonly known, fractional calculus has been incorporated into artificial neural networks, mainly because of its long-term memory and nonlocality. Some researchers have made interesting attempts at fractional neural networks and gained competitive advantages over integer-order neural networks. Therefore, it is naturally makes one ponder how to generalize the first-order Hopfield neural networks to the fractional-order ones, and how to implement FHNN by means of fractional calculus. We propose to introduce a novel mathematical method: fractional calculus to implement FHNN. First, we implement fractor in the form of an analog circuit. Second, we implement FHNN by utilizing fractor and the fractional steepest descent approach, construct its Lyapunov function, and further analyze its attractors. Third, we perform experiments to analyze the stability and convergence of FHNN, and further discuss its applications to the defense against chip cloning attacks for anticounterfeiting. The main contribution of our work is to propose FHNN in the form of an analog circuit by utilizing a fractor and the fractional steepest descent approach, construct its Lyapunov function, prove its Lyapunov stability, analyze its attractors, and apply FHNN to the defense against chip cloning attacks for anticounterfeiting. A significant advantage of FHNN is that its attractors essentially relate to the neuron's fractional order. FHNN possesses the fractional-order-stability and fractional-order-sensitivity characteristics.

  4. Ets-1 Confers Cranial Features on Neural Crest Delamination

    Science.gov (United States)

    Théveneau, Eric; Duband, Jean-Loup; Altabef, Muriel

    2007-01-01

    Neural crest cells (NCC) have the particularity to invade the environment where they differentiate after separation from the neuroepithelium. This process, called delamination, is strikingly different between cranial and trunk NCCs. If signalings controlling slow trunk delamination start being deciphered, mechanisms leading to massive and rapid cranial outflow are poorly documented. Here, we show that the chick cranial NCCs delamination is the result of two events: a substantial cell mobilization and an epithelium to mesenchyme transition (EMT). We demonstrate that ets-1, a transcription factor specifically expressed in cranial NCCs, is responsible for the former event by recruiting massively cranial premigratory NCCs independently of the S-phase of the cell cycle and by leading the gathered cells to straddle the basal lamina. However, it does not promote the EMT process alone but can cooperate with snail-2 (previously called slug) to this event. Altogether, these data lead us to propose that ets-1 plays a pivotal role in conferring specific cephalic characteristics on NCC delamination. PMID:17987123

  5. Ets-1 confers cranial features on neural crest delamination.

    Directory of Open Access Journals (Sweden)

    Eric Théveneau

    Full Text Available Neural crest cells (NCC have the particularity to invade the environment where they differentiate after separation from the neuroepithelium. This process, called delamination, is strikingly different between cranial and trunk NCCs. If signalings controlling slow trunk delamination start being deciphered, mechanisms leading to massive and rapid cranial outflow are poorly documented. Here, we show that the chick cranial NCCs delamination is the result of two events: a substantial cell mobilization and an epithelium to mesenchyme transition (EMT. We demonstrate that ets-1, a transcription factor specifically expressed in cranial NCCs, is responsible for the former event by recruiting massively cranial premigratory NCCs independently of the S-phase of the cell cycle and by leading the gathered cells to straddle the basal lamina. However, it does not promote the EMT process alone but can cooperate with snail-2 (previously called slug to this event. Altogether, these data lead us to propose that ets-1 plays a pivotal role in conferring specific cephalic characteristics on NCC delamination.

  6. Wnt/beta-catenin signaling plays an essential role in activation of odontogenic mesenchyme during early tooth development.

    Science.gov (United States)

    Chen, Jianquan; Lan, Yu; Baek, Jin-A; Gao, Yang; Jiang, Rulang

    2009-10-01

    Classical tissue recombination studies demonstrated that initiation of tooth development depends on activation of odontogenic potential in the mesenchyme by signals from the presumptive dental epithelium. Although several members of the Wnt family of signaling molecules are expressed in the presumptive dental epithelium at the beginning of tooth initiation, whether Wnt signaling is directly involved in the activation of the odontogenic mesenchyme has not been characterized. In this report, we show that tissue-specific inactivation of beta-catenin, a central component of the canonical Wnt signaling pathway, in the developing tooth mesenchyme caused tooth developmental arrest at the bud stage in mice. We show that mesenchymal beta-catenin function is required for expression of Lef1 and Fgf3 in the developing tooth mesenchyme and for induction of primary enamel knot in the developing tooth epithelium. Expression of Msx1 and Pax9, two essential tooth mesenchyme transcription factors downstream of Bmp and Fgf signaling, respectively, were not altered in the absence of beta-catenin in the tooth mesenchyme. Moreover, we found that constitutive stabilization of beta-catenin in the developing palatal mesenchyme induced aberrant palatal epithelial invaginations that resembled early tooth buds both morphologically and in epithelial molecular marker expression, but without activating expression of Msx1 and Pax9 in the mesenchyme. Together, these results indicate that activation of the mesenchymal odontogenic program during early tooth development requires concerted actions of Bmp, Fgf and Wnt signaling from the presumptive dental epithelium to the mesenchyme.

  7. Myelin plasticity, neural activity, and traumatic neural injury.

    Science.gov (United States)

    Kondiles, Bethany R; Horner, Philip J

    2018-02-01

    The possibility that adult organisms exhibit myelin plasticity has recently become a topic of great interest. Many researchers are exploring the role of myelin growth and adaptation in daily functions such as memory and motor learning. Here we consider evidence for three different potential categories of myelin plasticity: the myelination of previously bare axons, remodeling of existing sheaths, and the removal of a sheath with replacement by a new internode. We also review evidence that points to the importance of neural activity as a mechanism by which oligodendrocyte precursor cells (OPCs) are cued to differentiate into myelinating oligodendrocytes, which may potentially be an important component of myelin plasticity. Finally, we discuss demyelination in the context of traumatic neural injury and present an argument for altering neural activity as a potential therapeutic target for remyelination following injury. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 78: 108-122, 2018. © 2017 Wiley Periodicals, Inc.

  8. Different expression patterns of growth factors in rat fetuses with spina bifida aperta after in utero mesenchymal stromal cell transplantation.

    Science.gov (United States)

    Li, Hui; Miao, Jianing; Zhao, Guifeng; Wu, Di; Liu, Bo; Wei, Xiaowei; Cao, Songying; Gu, Hui; Zhang, Yi; Wang, Lili; Fan, Yang; Yuan, Zhengwei

    2014-03-01

    In a previous study, we successfully devised a prenatal surgical approach and transplanted mesenchymal stromal cells (MSCs) to fetal rat spinal column to treat retinoic acid-induced neural tube defects in rat. Our results show that MSCs survived, migrated and differentiated into neural lineage cells. We intended to study various growth factor expressions in rat fetal spinal cords with spina bifida aperta after in utero MSC transplantation and the effect of in vivo growth factor introduction for prenatal spina bifida treatment. Pregnant rats were treated with retinoic acid on embryonic day 10 and then received fetal surgery for MSC transplantation and/or lentiviral epidermal growth factor (EGF) injection on embryonic day 16; various growth factor expression in spinal cords from embryonic day 20 fetuses were analyzed by means of quantitative reverse transcriptase-polymerase chain reaction. Terminal deoxynucleotidyl transferase dUTP nick end labeling analysis was performed to observe spinal tissue apoptosis. Growth factor expression was dysregulated in spinal cords with spina bifida. After MSC transplantation, we observed significantly increased expression of EGF, fibroblast growth factor (FGF)-8, FGF-2 and FGF-20 in the MSC transplantation group compared with blank injection; Furthermore, EGF expression positively correlated with surviving MSC amounts. Expression of other growth factors was not significantly different. In vivo EGF introduction reduced spinal tissue apoptosis. Our results suggest that intrinsic EGF and FGF-2, FGF-8 and FGF-20 might affect the in vivo fate of transplanted MSCs in a fetal rat spina bifida model. In vivo EGF introduction together with MSC transplantation might serve as a new strategy for prenatal spina bifida treatment. Copyright © 2014 International Society for Cellular Therapy. All rights reserved.

  9. Reversine increases multipotent human mesenchymal cells differentiation potential.

    Science.gov (United States)

    Conforti, E; Arrigoni, E; Piccoli, M; Lopa, S; de Girolamo, L; Ibatici, A; Di Matteo, A; Tettamanti, G; Brini, A T; Anastasia, L

    2011-01-01

    Among different human stem cell sources, adult mesenchymal stem cells from bone marrow (BMSCs), and more recently from adipose tissues (ASCs), have shown their capability to differentiate into a variety of different cell types, including osteoblasts, adipocytes, and muscle cells. However, mesenchymal stem cell differentiation toward certain cell types (including skeletal and cardiac muscle), while shown to be achievable, still suffers of low yields and needs to be greatly improved before any therapeutic application could be foreseen. A possible way of achieving this goal is by using a chemical-pharmacological approach to increase stem cell plasticity. Along this line, we envisioned the possibility of pre-treating BMSCs and ASCs with reversine, a synthetic purine that has been shown to induce adult cells de-differentiation. In the current study we tested reversine effects on both BMSCs and ASCs to increase their differentiation toward osteoblasts, smooth and skeletal muscle cells. Reversine pre-treatment, at very low concentration (50 nM), caused a marked increase in the differentiation yields of both BMSCs and ASCs.

  10. Multilineage Potential Research of Bovine Amniotic Fluid Mesenchymal Stem Cells

    Directory of Open Access Journals (Sweden)

    Yuhua Gao

    2014-02-01

    Full Text Available The use of amnion and amniotic fluid (AF are abundant sources of mesenchymal stem cells (MSCs that can be harvested at low cost and do not pose ethical conflicts. In human and veterinary research, stem cells derived from these tissues are promising candidates for disease treatment, specifically for their plasticity, their reduced immunogenicity, and high anti-inflammatory potential. This work aimed to obtain and characterize bovine amniotic fluid mesenchymal stem cells (AFMSC. The bovine AF from the amniotic cavity of pregnant gilts in the early stages of gestation (3- and 4-m-old bovine embryos was collected. AFMSCs exhibit a fibroblastic-like morphology only starting from the fourth passage, being heterogeneous during the primary culture. Immunofluorescence results showed that AFMSCs were positive for β-integrin, CD44, CD73 and CD166, but negative for CD34, CD45. Meanwhile, AFMSCs expressed ES cell markers, such as Oct4, and when appropriately induced, are capable of differentiating into ectodermal and mesodermal lineages. This study reinforces the emerging importance of these cells as ideal tools in veterinary medicine; future studies aimed at a deeper evaluation of their immunological properties will allow a better understanding of their role in cellular therapy.

  11. Epithelial-to-mesenchymal transition in the development of endometriosis.

    Science.gov (United States)

    Yang, Yan-Meng; Yang, Wan-Xi

    2017-06-20

    Endometriosis, an estrogen-dependent chronic gynecological disease, is common in reproductive-age women and profoundly affects their life quality. Although various pathogenic theories have been proposed, the origin of endometriosis remains unclear. Epithelial to mesenchymal transition (EMT) is a process that epithelial cells lose polarized organization of the cytoskeleton and cell-to-cell contacts, acquiring the high motility of mesenchymal cells. These changes are thought to be prerequisites for the original establishment of endometriotic lesions. However, no study exactly indicates which type of EMT occurs in endometriosis. In this review, we conclude that two different types of EMT may participate in this disease. Besides, two stimulating signals, hypoxia and estrogen, can through different pathways to activate the EMT process in endometriosis. Those pathways involve many cellular factors such as TGF-beta and Wnt, ultimately leading to cell proliferation and migration. As infertility is becoming a serious and intractable issue for women, EMT, during the implantation process, is gaining attention. In this review, we will describe the known functions of EMT in endometriosis, and suggest further studies that may aid in the development of medical therapy.

  12. Regenerative Potential of Mesenchymal Stromal Cells: Age-Related Changes.

    Science.gov (United States)

    Bruna, Flavia; Contador, David; Conget, Paulette; Erranz, Benjamín; Sossa, Claudia L; Arango-Rodríguez, Martha L

    2016-01-01

    Preclinical and clinical studies have shown that a therapeutic effect results from mesenchymal stromal cells (MSCs) transplant. No systematic information is currently available regarding whether donor age modifies MSC regenerative potential on cutaneous wound healing. Here, we evaluate whether donor age influences this potential. Two different doses of bone marrow MSCs (BM-MSCs) from young, adult, or old mouse donors or two doses of their acellular derivatives mesenchymal stromal cells (acd-MSCs) were intradermally injected around wounds in the midline of C57BL/6 mice. Every two days, wound healing was macroscopically assessed (wound closure) and microscopically assessed (reepithelialization, dermal-epidermal junction, skin appendage regeneration, granulation tissue, leukocyte infiltration, and density dermal collagen fibers) after 12 days from MSC transplant. Significant differences in the wound closure kinetic, quality, and healing of skin regenerated were observed in lesions which received BM-MSCs from different ages or their acd-MSCs compared to lesions which received vehicle. Nevertheless, our data shows that adult's BM-MSCs or their acd-MSCs were the most efficient for recovery of most parameters analyzed. Our data suggest that MSC efficacy was negatively affected by donor age, where the treatment with adult's BM-MSCs or their acd-MSCs in cutaneous wound promotes a better tissue repair/regeneration. This is due to their paracrine factors secretion.

  13. Mesenchymal stem cell and osteoarthritis: a literature review

    Directory of Open Access Journals (Sweden)

    Zhaleh Shariati Sarabi

    2016-04-01

    Full Text Available The most common disease in the aged population is osteoarthritis (OA that is resulting in progressive dysfunction following isolated cartilage injuries, subchondral bone remodeling, tissue loss, marginal osteophytes, and loss of joint space. Mesenchymal stem cells (MSCs are multipotent stem cells; they are able to produce many or all joint tissues. Bone marrow and adipose tissue are rich sources of mesenchymal cells that are useful for the reconstruction of injured tissues such as bone, cartilage, or cardiac muscle. Recently, some studies have been performed on the use of the direct intra-articular injection of mononuclear cells (MNCs and MSCs as potential therapeutic targets in OA. In this review, the history of MSCs in the treatment of OA are explained. Injection of Bone Marrow Aspirates Concentrate (BMAC has significantly improved both joint pain and function in radiologic findings; some studies suggested that the injection would be even more effective in early to moderate phases of OA. Injection of MSCs in combination with growth factors may be better solution for the treatment.

  14. Mesenchymal stem cells for cartilage repair in osteoarthritis.

    Science.gov (United States)

    Gupta, Pawan K; Das, Anjan K; Chullikana, Anoop; Majumdar, Anish S

    2012-07-09

    Osteoarthritis (OA) is a degenerative disease of the connective tissue and progresses with age in the older population or develops in young athletes following sports-related injury. The articular cartilage is especially vulnerable to damage and has poor potential for regeneration because of the absence of vasculature within the tissue. Normal load-bearing capacity and biomechanical properties of thinning cartilage are severely compromised during the course of disease progression. Although surgical and pharmaceutical interventions are currently available for treating OA, restoration of normal cartilage function has been difficult to achieve. Since the tissue is composed primarily of chondrocytes distributed in a specialized extracellular matrix bed, bone marrow stromal cells (BMSCs), also known as bone marrow-derived 'mesenchymal stem cells' or 'mesenchymal stromal cells', with inherent chondrogenic differentiation potential appear to be ideally suited for therapeutic use in cartilage regeneration. BMSCs can be easily isolated and massively expanded in culture in an undifferentiated state for therapeutic use. Owing to their potential to modulate local microenvironment via anti-inflammatory and immunosuppressive functions, BMSCs have an additional advantage for allogeneic application. Moreover, by secreting various bioactive soluble factors, BMSCs can protect the cartilage from further tissue destruction and facilitate regeneration of the remaining progenitor cells in situ. This review broadly describes the advances made during the last several years in BMSCs and their therapeutic potential for repairing cartilage damage in OA.

  15. Regenerative Potential of Mesenchymal Stromal Cells: Age-Related Changes

    Science.gov (United States)

    Bruna, Flavia; Contador, David; Conget, Paulette; Erranz, Benjamín; Sossa, Claudia L.; Arango-Rodríguez, Martha L.

    2016-01-01

    Preclinical and clinical studies have shown that a therapeutic effect results from mesenchymal stromal cells (MSCs) transplant. No systematic information is currently available regarding whether donor age modifies MSC regenerative potential on cutaneous wound healing. Here, we evaluate whether donor age influences this potential. Two different doses of bone marrow MSCs (BM-MSCs) from young, adult, or old mouse donors or two doses of their acellular derivatives mesenchymal stromal cells (acd-MSCs) were intradermally injected around wounds in the midline of C57BL/6 mice. Every two days, wound healing was macroscopically assessed (wound closure) and microscopically assessed (reepithelialization, dermal-epidermal junction, skin appendage regeneration, granulation tissue, leukocyte infiltration, and density dermal collagen fibers) after 12 days from MSC transplant. Significant differences in the wound closure kinetic, quality, and healing of skin regenerated were observed in lesions which received BM-MSCs from different ages or their acd-MSCs compared to lesions which received vehicle. Nevertheless, our data shows that adult's BM-MSCs or their acd-MSCs were the most efficient for recovery of most parameters analyzed. Our data suggest that MSC efficacy was negatively affected by donor age, where the treatment with adult's BM-MSCs or their acd-MSCs in cutaneous wound promotes a better tissue repair/regeneration. This is due to their paracrine factors secretion. PMID:27247575

  16. Hypoxia activated EGFR signaling induces epithelial to mesenchymal transition (EMT.

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    Ashish Misra

    Full Text Available Metastasis is a multi-step process which requires the conversion of polarized epithelial cells to mesenchymal cells, Epithelial-Mesenchymal Transition (EMT. EMT is essential during embryonic morphogenesis and has been implicated in the progression of primary tumors towards metastasis. Hypoxia is known to induce EMT; however the molecular mechanism is still poorly understood. Using the A431 epithelial cancer cell line, we show that cells grown under hypoxic conditions migrated faster than cells grown under normal oxygen environment. Cells grown under hypoxia showed reduced adhesion to the extracellular matrix (ECM probably due to reduced number of Vinculin patches. Growth under hypoxic conditions also led to down regulation of E-cadherin and up regulation of vimentin expression. The increased motility of cells grown under hypoxia could be due to redistribution of Rac1 to the plasma membrane as opposed to increased expression of Rac1. EGF (Epidermal Growth Factor is a known inducer of EMT and growth of A431 cells in the absence of oxygen led to increased expression of EGFR (EGF Receptor. Treatment of A431 cells with EGF led to reduced cell adhesion to ECM, increased cell motility and other EMT characteristics. Furthermore, this transition was blocked by the monoclonal antibody Cetuximab. Cetuximab also blocked the hypoxia-induced EMT suggesting that cell growth under hypoxic conditions led to activation of EGFR signaling and induction of EMT phenotype.

  17. Melatonin regulates mesenchymal stem cell differentiation: a review.

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    Luchetti, Francesca; Canonico, Barbara; Bartolini, Desirée; Arcangeletti, Marcella; Ciffolilli, Silvia; Murdolo, Giuseppe; Piroddi, Marta; Papa, Stefano; Reiter, Russel J; Galli, Francesco

    2014-05-01

    Among the numerous functions of melatonin, the control of survival and differentiation of mesenchymal stem cells (MSCs) has been recently proposed. MSCs are a heterogeneous population of multipotent elements resident in tissues such as bone marrow, muscle, and adipose tissue, which are primarily involved in developmental and regeneration processes, gaining thus increasing interest for tissue repair and restoration therapeutic protocols. Receptor-dependent and receptor-independent responses to melatonin are suggested to occur in these cells. These involve antioxidant or redox-dependent functions of this indolamine as well as secondary effects resulting from autocrine and paracrine responses. Inflammatory cytokines and adipokines, proangiogenic/mitogenic stimuli, and other mediators that influence the differentiation processes may affect the survival and functional integrity of these mesenchymal precursor cells. In this scenario, melatonin seems to regulate signaling pathways that drive commitment and differentiation of MSC into osteogenic, chondrogenic, adipogenic, or myogenic lineages. Common pathways suggested to be involved as master regulators of these processes are the Wnt/β-catenin pathway, the MAPKs and the, TGF-β signaling. In this respect melatonin emerges a novel and potential modulator of MSC lineage commitment and adipogenic differentiation. These and other aspects of the physiological and pharmacological effects of melatonin as regulator of MSC are discussed in this review. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Epithelial to Mesenchymal Transition in a Clinical Perspective

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    Jennifer Pasquier

    2015-01-01

    Full Text Available Tumor growth and metastatic dissemination rely on cellular plasticity. Among the different phenotypes acquired by cancer cells, epithelial to mesenchymal transition (EMT has been extensively illustrated. Indeed, this transition allows an epithelial polarized cell to acquire a more mesenchymal phenotype with increased mobility and invasiveness. The role of EMT is quite clear during developmental stage. In the neoplastic context in many tumors EMT has been associated with a more aggressive tumor phenotype including local invasion and distant metastasis. EMT allows the cell to invade surrounding tissues and survive in the general circulation and through a stem cell phenotype grown in the host organ. The molecular pathways underlying EMT have also been clearly defined and their description is beyond the scope of this review. Here we will summarize and analyze the attempts made to block EMT in the therapeutic context. Indeed, till today, most of the studies are made in animal models. Few clinical trials are ongoing with no obvious benefits of EMT inhibitors yet. We point out the limitations of EMT targeting such tumor heterogeneity or the dynamics of EMT during disease progression.

  19. The WTX Tumor Suppressor Regulates Mesenchymal Progenitor Cell Fate Specification

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    Lotinun, Sutada; Akhavanfard, Sara; Coffman, Erik J.; Cook, Edward B.; Stoykova, Svetlana; Mukherjee, Siddhartha; Schoonmaker, Jesse A.; Burger, Alexa; Kim, Woo Jae; Kronenberg, Henry M.; Baron, Roland; Haber, Daniel A.; Bardeesy, Nabeel

    2014-01-01

    SUMMARY WTX is an X-linked tumor suppressor targeted by somatic mutations in Wilms tumor, a pediatric kidney cancer, and by germline inactivation in osteopathia striata with cranial sclerosis, a bone overgrowth syndrome. Here, we show that Wtx deletion in mice causes neonatal lethality, somatic overgrowth, and malformation of multiple mesenchyme-derived tissues, including bone, fat, kidney, heart, and spleen. Inactivation of Wtx at different developmental stages and in primary mesenchymal progenitor cells (MPCs) reveals that bone mass increase and adipose tissue deficiency are due to altered lineage fate decisions coupled with delayed terminal differentiation. Specification defects in MPCs result from aberrant β-catenin activation, whereas alternative pathways contribute to the subsequently delayed differentiation of lineage-restricted cells. Thus, Wtx is a regulator of MPC commitment and differentiation with stage-specific functions in inhibiting canonical Wnt signaling. Furthermore, the constellation of anomalies in Wtx null mice suggests that this tumor suppressor broadly regulates MPCs in multiple tissues. PMID:21571217

  20. Vascular Remodelling and Mesenchymal Transition in Systemic Sclerosis

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    Pier Andrea Nicolosi

    2016-01-01

    Full Text Available Fibrosis of the skin and of internal organs, autoimmunity, and vascular inflammation are hallmarks of Systemic Sclerosis (SSc. The injury and activation of endothelial cells, with hyperplasia of the intima and eventual obliteration of the vascular lumen, are early features of SSc. Reduced capillary blood flow coupled with deficient angiogenesis leads to chronic hypoxia and tissue ischemia, enforcing a positive feed-forward loop sustaining vascular remodelling, further exacerbated by extracellular matrix accumulation due to fibrosis. Despite numerous developments and a growing number of controlled clinical trials no treatment has been shown so far to alter SSc natural history, outlining the need of further investigation in the molecular pathways involved in the pathogenesis of the disease. We review some processes potentially involved in SSc vasculopathy, with attention to the possible effect of sustained vascular inflammation on the plasticity of vascular cells. Specifically we focus on mesenchymal transition, a key phenomenon in the cardiac and vascular development as well as in the remodelling of injured vessels. Recent work supports the role of transforming growth factor-beta, Wnt, and Notch signaling in these processes. Importantly, endothelial-mesenchymal transition may be reversible, possibly offering novel cues for treatment.