Mesenchymal stem cells regulate the proliferation and differentiation of neural stem cells through Notch signaling

Institute of Urology, Nanchang University, Nanchang 330006, China.
Cell Biology International (Impact Factor: 1.93). 09/2009; 33(11):1173-9. DOI: 10.1016/j.cellbi.2009.08.004
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The effects of mesenchymal stem cells (MSCs) on proliferation and cell fate determination of neural stem cells (NSCs) have been investigated. NSCs were co-cultured with MSCs or NIH3T3 cells using an in vitro transwell system. After 4 days, immunofluorescence staining showed that the number of cells positive for the cell proliferation antigen, ki-67, in neurospheres in MSCs was greater than in NIH3T3 cells. In some experiments, the top-layers of MSCs and NIH3T3 cells were removed to induce NSCs differentiation. Seven days after initiating differentiation, the levels of the neuronal marker, NSE, were higher in NSCs in MSCs co-culture group, and those of glial fibrillary acidic protein (GFAP) were lower, compared with NIH3T3 cells co-culture group. These were confirmed by immunofluorescence. The role of the Notch signaling pathway analyzed with the specific inhibitor, DAPT, and by examining the expression of Notch-related genes using RT-PCR showed that after co-culturing with MSCs for 24h, NSCs expressed much higher levels of ki-67, Notch1, and Hes1 than did NSCs co-cultured with NIH3T3 cells. Treatment with DAPT decreased ki-67, Notch1 and Hes1 expression in NCSs, and increased Mash1 expression. The data indicate that the interactions between MSCs and NSCs promote NSCs proliferation and are involved in specifying neuronal fate, mediated in part by Notch signaling.

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Available from: Yang Wang, Oct 03, 2015
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    • "In other systems, Notch signaling acts to coordinate proliferation and differentiation, as observed, for example, with mammalian Notch1, which is necessary for both the proliferation of neuronal stem cell populations and their differentiation into specific neuronal types (Hitoshi et al. 2002; Wang et al. 2009; Ables et al. 2010; Zhou et al. 2010; Matsumoto et al. 2011). We showed that in C. elegans, Notch can act not only as a factor in specifying cell types, but also, through an apparently distinct process, in the general restriction of developmental plasticity. "
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    ABSTRACT: We report that Notch signaling is essential for the switch from developmental plasticity to commitment during Caenorhabditis elegans embryogenesis. The GLP-1 and LIN-12 Notch receptors act to set a memory state that affects commitment of cells arising from the major ectodermal progenitor (AB blastomere) several cell divisions later, thereby preventing their forced reprogramming by an endoderm-determining transcription factor. In contrast to Notch-dependent cell fate induction, this activity is autonomous to the AB lineage, is independent of the known cell fate-inducing Notch ligands, and requires a putative secreted Notch ligand, Delta Serrate Lag-3 (DSL-3). Thus, Notch signaling promotes developmental commitment by a mechanism that is distinct from that involved in specifying cell fates.
    Genes & development 11/2012; 26(21):2386-91. DOI:10.1101/gad.199588.112 · 10.80 Impact Factor
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    • "The proteomic analysis of MSC indicated that MSCs include growth factor receptors such as TGF-β, FGF, and EGF. These receptors have the ability to initiate the intracellular signaling cascade related to neural differentiation, such as Wnt, Notch/delta, and TGF-β [32, 38, 61, 62]. Although the evidence is still lacking for the age-dependent expression profile of ocular growth factors or cytokines in the vitreous fluid, the VIGF, IGF-1, and GH related to neovascularization and development of the eye were decreased in rat vitreous fluid in proportion to advancing postnatal age [3, 6, 39]. "
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    ABSTRACT: Mesenchymal stem cells (MSCs) have been studied widely for their potential to differentiate into various lineage cells including neural cells in vitro and in vivo. To investigate the influence of the developing host environment on the integration and morphological and molecular differentiation of MSCs, human bone marrow-derived mesenchymal stem cells (BM-MSCs) were transplanted into the developing mouse retina. Enhanced green fluorescent protein (GFP)-expressing BM-MSCs were transplanted by intraocular injections into mice, ranging in ages from 1 day postnatal (PN) to 10 days PN. The survival dates ranged from 7 days post-transplantation (DPT) to 28DPT, at which time an immunohistochemical analysis was performed on the eyes. The transplanted BM-MSCs survived and showed morphological differentiation into neural cells and some processes within the host retina. Some transplanted cells expressed microtubule associated protein 2 (MAP2ab, marker for mature neural cells) or glial fibrillary acid protein (GFAP, marker for glial cells) at 5PN 7DPT. In addition, some transplanted cells integrated into the developing retina. The morphological and molecular differentiation and integration within the 5PN 7DPT eye was greater than those of other-aged host eye. The present findings suggest that the age of the host environment can strongly influence the differentiation and integration of BM-MSCs.
    ACTA HISTOCHEMICA ET CYTOCHEMICA 10/2011; 44(5):213-21. DOI:10.1267/ahc.11009 · 1.39 Impact Factor
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    ABSTRACT: Preparation of soft poly(amino acid) hydrogels containing biomimetic cell-adhesive peptides was investigated. Covalently crosslinked gels were formed by radical co-polymerization of methacryloylated macromonomer poly[N(5)-(2-hydroxyethyl)-L-glutamine-stat-L-alanine-stat-methacryloyllysine] with 2-hydroxyethyl methacrylate (HEMA) as minor co-monomer. Hydrogels carrying biomimetic peptides were prepared by using methacryloylated peptides, such as methacryloyl-GGGRGDSG-OH and methacryloyl-GGGYIGSR-OH, as additional monomers in the polymerization mixture. Mechanical stability and swelling in water of the hydrogels obtained for different solid:water and polypeptide:HEMA ratios were evaluated. The microporosity of gels (5-20 microm), dependent on the polyHEMA phase separation in water, was followed by low-vacuum SEM. The effect of biomimetic modification of hydrogels with RGDS and YIGSR peptides on the seeding efficiency of porcine mesenchymal stem cells (MSCs) was studied in vitro. While unmodified hydrogels showed very low cell adhesion, due to their highly hydrophilic nature, the incorporation of adhesive peptides significantly improved the adhesion and viability of seeded cells.
    Journal of Tissue Engineering and Regenerative Medicine 08/2010; 4(6):454-63. DOI:10.1002/term.256 · 5.20 Impact Factor
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