Search results for "Cellular differentiation"
showing 10 items of 482 documents
Improving mRNA-Based Therapeutic Gene Delivery by Expression-Augmenting 3' UTRs Identified by Cellular Library Screening.
2019
Synthetic mRNA has emerged as a powerful tool for the transfer of genetic information, and it is being explored for a variety of therapeutic applications. Many of these applications require prolonged intracellular persistence of mRNA to improve bioavailability of the encoded protein. mRNA molecules are intrinsically unstable and their intracellular kinetics depend on the UTRs embracing the coding sequence, in particular the 3′ UTR elements. We describe here a novel and generally applicable cell-based selection process for the identification of 3′ UTRs that augment the expression of proteins encoded by synthetic mRNA. Moreover, we show, for two applications of mRNA therapeutics, namely, (1) …
In vitro and in vivo arterial differentiation of human multipotent adult progenitor cells
2006
Many stem cell types have been shown to differentiate into endothelial cells (ECs); however, their specification to arterial or venous endothelium remains unexplored. We tested whether a specific arterial or venous EC fate could be induced in human multipotent adult progenitor cells (hMAPCs) and AC133(+) cells (hAC133(+)). In vitro, in the presence of VEGF(165), hAC133(+) cells only adopted a venous and microvascular EC phenotype, while hMAPCs differentiated into both arterial and venous ECs, possibly because hMAPCs expressed significantly more sonic hedgehog (Shh) and its receptors as well as Notch 1 and 3 receptors and some of their ligands. Accordingly, blocking either of those pathways …
Let it flow: Morpholino knockdown in zebrafish embryos reveals a pro-angiogenic effect of the metalloprotease meprin alpha2.
2010
BACKGROUND: Meprin metalloproteases are thought to be involved in basic physiological functions such as cell proliferation and tissue differentiation. However, the specific functions of these enzymes are still ambiguous, although a variety of growth factors and structural proteins have been identified as meprin substrates. The discovery of meprins alpha(1), alpha(2) and beta in teleost fish provided the basis for uncovering their physiological functions by gene silencing in vivo. METHODOLOGY/PRINCIPAL FINDINGS: A Morpholino knockdown in zebrafish embryos targeting meprin alpha(1) and beta mRNA caused defects in general tissue differentiation. But meprin alpha(2) morphants were affected more…
Tbx1 regulates Vegfr3 and is required for lymphatic vessel development
2010
Defects in lymphangiogenesis are added to the broad clinical manifestations of DiGeorge syndrome, caused by deletion of the T box transcription factor Tbx1.
Sonic hedgehog promotes angiogenesis and osteogenesis in a coculture system consisting of primary osteoblasts and outgrowth endothelial cells.
2009
A number of previous studies documented the angiogenic potential of outgrowth endothelial cells in vitro and in vivo and provided evidence that therapeutic success could depend on coculture or coimplantation strategies. Thus, deeper insight into the molecular mechanisms underlying this pro-angiogenic effect of cocultures might provide new translational options for tissue engineering and regenerative medicine. One promising signaling pathway in bone repair involved in neoangiogenesis and bone formation is the sonic hedgehog (Shh) pathway. In this article, we focus on the effect of Shh on the formation of microvessel-like structures and osteoblastic differentiation in cocultures of primary os…
Prediction model for aneuploidy in early human embryo development revealed by single-cell analysis.
2014
Aneuploidies are prevalent in the human embryo and impair proper development, leading to cell cycle arrest. Recent advances in imaging and molecular and genetic analyses are postulated as promising strategies to unveil the mechanisms involved in aneuploidy generation. Here we combine time-lapse, complete chromosomal assessment and single-cell RT–qPCR to simultaneously obtain information from all cells that compose a human embryo until the approximately eight-cell stage (n=85). Our data indicate that the chromosomal status of aneuploid embryos (n=26), including those that are mosaic (n=3), correlates with significant differences in the duration of the first mitotic phase when compared with e…
Molecular mechanisms in developmental biology.
1996
Some general molecular mechanisms underlying development are described. Namely: those involved in the differentiation of the R7 receptor in Drosophila embryonic retina; those involved in the determination of embryonic axes and in polar cell differentiation, in Drosophila; those involved in the determination of the AB and P cell lineage and in vulva differentiation in Caenorhabditis embryos.
Role of GATA-1 and HSP70 in the Dyserythropoiesis of Early Myelodysplastic Syndromes.
2009
Abstract Abstract 3823 Poster Board III-759 Myelodysplastic syndromes (MDS) are heterogeneous hematopoietic stem cell disorders characterized by a hypercellular dysplastic bone marrow (BM) with peripheral blood cytopenias, mainly anemia. Early MDS with less than 10% BM blasts which belong in most cases to low and intermediate-1 (int-1) risk groups according to the International Prognostic Scoring System (IPSS), usually demonstrate dyserythropoiesis. The growth of erythroid progenitors is altered, with increased caspase activation leading to excessive cell death, and cellular dysplasia characterized, in liquid culture of CD34+-derived erythroid progenitors, by a delayed expression of the gly…
Long-term response of osteogenic cells on micron and submicron-scale-structured hydrophilic titanium surfaces: sequence of cell proliferation and cel…
2010
Objective: Modifications of surface topography and surface chemistry are key factors for guiding target cells during dental implant healing. Recent in vitro studies confirmed promotion of early osteogenic cell differentiation on submicron scaled surfaces in particular when hydrophilized. However, no long-term observations on both osteogenic cell proliferation as well as on cell maturation have been reported for respectively modified surfaces. Aim of this study was to monitor osteogenic cell proliferation and expression of specific osteogenic cell differentiation markers on a protein level over an extended period of 3 weeks with respect to surface modifications. Material and methods: Modifie…
Submicron Scale-Structured Hydrophilic Titanium Surfaces Promote Early Osteogenic Gene Response for Cell Adhesion and Cell Differentiation
2011
cid_339 166..175 ABSTRACT Background and Purpose: Titanium (Ti) surface roughness and surface hydrophilicity are key factors to regulate osteogenic cell responses during dental implant healing. In detail, specific integrin-mediated interactions with the extracellular environment trigger relevant osteogenic cell responses like differentiation and matrix synthesis via transcriptions factors. Aim of this study was to monitor surface-dependent osteogenic cell adhesion dynamics, proliferation, and specific osteo- genic cell differentiation over a period of 7 days. Materials and Methods: Ti disks were manufactured to present smooth pretreatment (PT) surfaces and rough sandblasted/ acid-etched (SL…