Morphological and Functional Characterization of Predifferentiation of Myelinating Glia-Like Cells from Human Bone Marrow Stromal Cells Through Activation of F3/Notch Signaling in Mouse Retina

Lu, Li; Chen, Xue; Zhang, Chengwu; Yang, Wulin; Wu, Yajun; Lee, Sun; Li-min, Bai; Gu, Xiaosong; Ahmed, Sohail; Dawe, Gavin S.; Xiao, Zhicheng

doi:10.1634/stemcells.2007-0106

Cited by 50 publications

(31 citation statements)

References 49 publications

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“…MSCs-based cell therapy has shown great significance in treating a broad spectrum of diseases, including peripheral nerve injuries [6,7,10]. For exploring the action mechanisms of MSCs, it was postulated that the implanted MSCs differentiate into functional neural cells at the injured site of peripheral nervous system, but there seems to be a dearth of well-defined experimental data to support this viewpoint.…”

Section: Discussionmentioning

confidence: 99%

“…The inclusion of MSCs in tissue-engineered nerve grafts has been tried for peripheral nerve repair, achieving an improved nerve regeneration and functional recovery [6][7][8][9][10]. However, the mechanisms that determine how the implanted MSCs promote peripheral nerve repair remain controversial and unclear.…”

Section: Introductionmentioning

confidence: 99%

“…However, the mechanisms that determine how the implanted MSCs promote peripheral nerve repair remain controversial and unclear. Some people hold a transdifferentiation mechanism of MSCs because MSCs can not only be differentiated into neural lineages including neurons, astrocytes, oligodendrocytes, microglia, and Schwann cells (SCs)-like in vitro [7,9,[11][12][13][14][15], but can generate neural phenotypes specific to the lesion site after implanted in vivo [16][17][18][19]. Other people believe that the so-called transdifferentiation is nothing but spontaneous fusion of MSCs with host cells [20,21].…”

Section: Introductionmentioning

confidence: 99%

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Effects of Bone Marrow Stromal Cell-conditioned Medium on Primary Cultures of Peripheral Nerve Tissues and Cells

Yang

et al. 2009

Neurochem Res

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Implantation of bone marrow stromal cells (MSCs) produces an improved functional outcome of peripheral nerve repair. In this study, rat dorsal root ganglion (DRG) explants, rat DRG neurons, and rat Schwann cells (SCs) were treated with monkey MSC-conditioned medium, respectively, and then subjected to MTT assay, Bromodeoxyuridine/Hoechst 33342 double staining, flow cytometry, immunohistochemistry, real-time quantitative PCR, and Western blot analysis, respectively. The results showed that MSC-conditioned medium enhanced axon growth and neurogenesis in cultured DRG explants, augmented cell survival of and expression of NF and GAP-43 by cultured DRG neurons, promoted cell survival and proliferation of cultured SCs, and increased the expression of NGF, BDNF, and bFGF in cultured SCs. We also found that mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (Erk) 1/2 pathway was involved in the enhanced cell proliferation of SCs evoked by MSC-conditioned medium. The data of this study might help the understanding of MSCs-based treatment for peripheral nerve repair.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effects of Bone Marrow Stromal Cell-conditioned Medium on Primary Cultures of Peripheral Nerve Tissues and Cells

Yang

et al. 2009

Neurochem Res

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“…The cells have been demonstrated to promote functional recovery as well as tissue regeneration in rat models with spinal cord injury (Wu et al 2003;Ohta et al 2004), cerebral ischemia (Chen et al 2001a(Chen et al , b, c, 2002a(Chen et al , b, 2003Li et al 2002), or traumatic brain injury (Lu et al , 2002Mahmood et al, 2001Mahmood et al, , 2003Mahmood et al, , 2004Mahmood et al, , 2006. Also, the inclusion of BMSCs represents a novel avenue for constructing tissue-engineered nerve grafts used for peripheral nerve repair (Chen et al 2000(Chen et al , 2006aDezawa et al 2005;Lu et al 2008;Wang et al 2008). However, controversy remains on the issue of what are responsible for the positive effects of BMSCs on nerve regeneration.…”

Section: Introductionmentioning

confidence: 99%

“…However, controversy remains on the issue of what are responsible for the positive effects of BMSCs on nerve regeneration. Some researchers claim that BMSCs can be transdifferentiated into neural lineages including neurons, astrocytes, oligodendrocytes, microglia, and Schwann cell (SC)-like in vitro (Woodbury et al 2000;Munoz-Elias et al 2003;Suzuki et al 2004;Wislet-Gendebien et al 2005;Chen et al 2006a, b;Lu et al 2008), and the implanted BMSCs generate neural phenotypes specific to the lesion site in vivo (Kopen et al 1999;Lu et al 2001Lu et al , 2006Mahmood et al 2001;Kocsis et al 2002;Coyne et al 2006). Other researchers believe that the implanted BMSCs exert neurotrophic functions through producing an array of soluble factors or via a direct cell-to-cell contact rather than replacement of damaged nerve tissues and cells (Chopp and Li 2002;Zhong et al 2003;Neuhuber et al 2005;Caplan and Dennis 2006).…”

Section: Introductionmentioning

confidence: 99%

Neurotrophic Actions of Bone Marrow Stromal Cells on Primary Culture of Dorsal Root Ganglion Tissues and Neurons

Wang

Ding

et al. 2009

J Mol Neurosci

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Application of adult bone marrow stromal cells (BMSCs) provides therapeutic benefits to the treatment of neurological insults. The aim of this study was to explore the potential of nonhematopoietic BMSCs to produce soluble factors and stimulate signaling pathways in neurons that mediate trophic effects. A combination of enzyme-linked immunosorbent assay and two-dimensional gel electrophoresis coupled with mass spectrometry showed that the BMSCs released into the culture medium an array of soluble factors such as nerve growth factor, brain-derived neurotrophic factor, basic fibroblast growth factor, and ciliary neurotrophic factor, which have been shown to exhibit potent neurotrophic effects on neural cells. Immunochemistry, cell viability assay, and quantitative real-time RT-PCR collectively showed that neurite outgrowth and neurogenesis in cultured rat dorsal root ganglion (DRG) explants and neurons were enhanced after they were cocultured with rat BMSCs. Western blot analysis revealed that BMSC-conditioned medium activated phosphorylation of mitogen-activated protein kinase/extracellular signal-regulated protein kinase and/or phosphoinositide 3-kinase/serine/threonine kinase (PI3K/Akt) in primary culture of rat DRG neurons, which suggested that BMSCs trigger endogenous survival signaling pathways in neurons through their secreted soluble factors. Our data help to elucidate the mechanisms by which BMSCs function as a cell therapy agent in peripheral nerve regeneration.

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The gene encoding the mouse contactin‐1 axonal glycoprotein is regulated by the collier/Olf1/EBF family early B‐Cell factor 2 transcription factor

Bizzoca

Picocci

Corsi

et al. 2015

Developmental Neurobiology

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The Contactin-1 axonal glycoprotein (formerly F3/Contactin) plays a relevant role in cerebellar ontogenesis, as shown in Contactin-1 KO-mice and in transgenic mice misexpressing the corresponding cDNA from a heterologous promoter. Likewise, null mutant mice for the Collier/Olf1/Early B-cell family transcription factor EBF2, in which Purkinje neuron development is primarily affected, exhibit abnormalities in cerebellar corticogenesis. Here, to evaluate the contribution to the Ebf2 null phenotype of changes in the profile of Contactin-1, we study its expression in Ebf2 null mice. In addition, we explore the activation profile of the Cntn1 gene promoter upon transferring the Ebf2 mutation to transgenic mice expressing an enhanced green fluorescent protein reporter under control of Cntn1 gene regulatory sequences. In Ebf2 null mice, Contactin-1 protein expression and Cntn1 gene promoter activity are both downregulated during embryonic and early postnatal cerebellar development, both in the rostral and caudal folia, while in the latter an upregulation is observed at postnatal day 8. In vitro, vectors driving EBF1,2,3 transcription factors from a cytomegalovirus (CMV) promoter transactivate a Cntn1-Choline acetyltransferse (CAT) promoter-reporter construct in cotransfection assays and, accordingly, by chromatin immunoprecipitation, we show that the Cntn1 gene 5' flanking region is bound by the EBF2 transcription factor, consistent with the evidence that this region bears the cognate deoxyribonucleic acid (DNA) consensus sequences. These data indicate that Contactin-1 expression is dependent upon EBF factors, suggesting that the Cntn1 gene belongs to the expanding regulatory cascade driven by these transcriptional regulators so that changes in its activation may contribute to the phenotype of Ebf2 null mutant mice.

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Morphological and Functional Characterization of Predifferentiation of Myelinating Glia-Like Cells from Human Bone Marrow Stromal Cells Through Activation of F3/Notch Signaling in Mouse Retina

Abstract: STEM CELLS 2008;26:580 -590 Disclosure of potential conflicts of interest is found at the end of this article.

Cited by 50 publications

References 49 publications

Effects of Bone Marrow Stromal Cell-conditioned Medium on Primary Cultures of Peripheral Nerve Tissues and Cells

Effects of Bone Marrow Stromal Cell-conditioned Medium on Primary Cultures of Peripheral Nerve Tissues and Cells

Neurotrophic Actions of Bone Marrow Stromal Cells on Primary Culture of Dorsal Root Ganglion Tissues and Neurons

The gene encoding the mouse contactin‐1 axonal glycoprotein is regulated by the collier/Olf1/EBF family early B‐Cell factor 2 transcription factor

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