Efficient gene transfer of a simian immuno‐deficiency viral vector into cardiomyocytes derived from primate embryonic stem cells

Nagata, Mihoko; Takahashi, Masafumi; Muramatsu, Shin‐ichi; Ueda, Yasuji; Hanazono, Yutaka; Takeuchi, Koichi; Okada, Koji; Suzuki, Yutaka; Kondo, Yasushi; Suemori, Masafumi; Ikeda, Uichi; Nakano, Imaharu; Kobayashi, Eiji; Hasegawa, Mamoru; Ozawa, Keiya; Nakatsuji, Norio; Shimada, Kazuyuki

doi:10.1002/jgm.431

Cited by 9 publications

(8 citation statements)

References 31 publications

(35 reference statements)

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“…[33][34][35][36][37] We elected to use SIVderived lentiviral vectors for this study based on reports that they are more efficient for transduction of simian stem cells. 19,20,[38][39][40] Our results using SIV-based aGT constructs are consistent with those findings. Under nonmyeloablative conditions, however, we were not able to achieve the levels of engraftment reported by Hanawa et al 19 using an SIV-based EGFP-expressing vector (marking up to 14% of CD3 + and 17% CD20 + cells 7 months after transfer).…”

Section: Discussionsupporting

confidence: 91%

Gene therapy to inhibit xenoantibody production using lentiviral vectors in non-human primates

et al. 2006

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Section: Discussionsupporting

confidence: 91%

Gene therapy to inhibit xenoantibody production using lentiviral vectors in non-human primates

et al. 2006

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“…We employed a lentivirus-based transfection system to either overexpress NDRG1 cDNA or silence NDRG1 expression using siRNA. vesicular stomatitis virus-G-pseudotyped lentiviral vectors, which exhibit broad transduction efficiency and thereby expanded virus infectivity, have been used to transduce transgenes in differentiated cells and diverse tissues including neurons (35,68), liver (69), muscle (70), and retina (71) as well as undifferentiated stem cells and embryos (72,73). The broad virus tropism is attributed to the ability of the vesicular stomatitis virus-G protein to bind phosphatidyl serine in the lipid bilayer of the cell membrane of most eukaryotic cells (74).…”

Section: Discussionmentioning

confidence: 99%

N-Myc Down-regulated Gene 1 Modulates the Response of Term Human Trophoblasts to Hypoxic Injury

Chen

Nelson

Sadovsky

2006

Journal of Biological Chemistry

125

116

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The placenta is susceptible to diverse insults during human pregnancy. The expression of the protein N-myc down-regulated gene 1 (NDRG1) is regulated during cell proliferation, differentiation, and in response to stress. Nevertheless, the function of this protein in humans remains unknown. We tested the hypothesis that NDRG1 is up-regulated in hypoxic primary human trophoblasts and that NDRG1 modulates trophoblast response to hypoxia. We initially demonstrated that the expression of NDRG1 is enhanced in primary human trophoblasts exposed to hypoxia. Importantly, we found a similar increase in NDRG1 expression in placental samples derived from either singleton gestations complicated by intrauterine growth restriction or from dizygotic twin gestation where one twin exhibited growth restriction. Having established efficient lentivirus-mediated transfection of primary human trophoblasts, we overexpressed NDRG1 in trophoblasts, which resulted in enhanced trophoblast differentiation. In contrast, lentivirus-driven short interfering RNA-mediated silencing of NDRG1 diminished trophoblast viability and differentiation. Consistent with these results, NDRG1 reduced the expression level of p53 in trophoblasts cultured in standard or hypoxic conditions. Furthermore, NDRG1 expression was regulated by the activity of SIRT1 (Sir2-like protein 1), which promotes cell survival. Together, our data indicate that NDRG1 interacts with SIRT1/p53 signaling to attenuate hypoxic injury in human trophoblasts.The trophoblasts at the surface of human placental villi play a pivotal role in gas exchange, nutrition, waste removal, endocrine function, and immunological support for the developing fetus. Trophoblast invasion and early placental development occur in an environment of relative hypoxia (1, 2). Under these conditions hypoxia promotes invasion and angiogenesis (3) and is associated with up-regulation of vascular endothelial growth factor expression and down-regulation of placenta growth factor (4, 5). Trophoblast hypoxia later in pregnancy commonly stems from placental hypoperfusion, vasoconstriction, maternal systemic disease, high altitude, or smoking and may result in hypoxic injury to the placenta and consequently intrauterine growth restriction (IUGR) 2 with its consequences (6).Using high density oligonucleotide microarrays we have previously examined differences in gene expression between placental tissues from pregnancies complicated by IUGR versus matched normal placental tissues as well as from trophoblasts cultured under hypoxic or standard culture conditions (7,8). Combining these paradigms, we characterized a set of hypoxic trophoblast signature transcripts (8). Among these transcripts we consistently identified up-regulation of NDRG1 (N-myc down-regulated gene 1) transcript in hypoxic trophoblasts compared with cells cultured in standard conditions (8).3 NDRG1 (also called RTP, Drg1, Cap 43, rit42, TDD5, Ndr1, and PROXY-1) is a 394-amino acid protein expressed in both the cytoplasm and nucleus (9 -16) and implicated in c...

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“…For the mouse genes, the primer sequences and cycles are listed in Supplementary Table 1. The primers for the monkey genes were the same as designed previously (Nagata et al, 2003;Sumi et al, 2004).…”

Section: Rt-pcrmentioning

confidence: 99%

Activation of Akt signaling is sufficient to maintain pluripotency in mouse and primate embryonic stem cells

et al. 2006

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Embryonic stem (ES) cells can self-renew indefinitely without losing their differentiation ability to any cell types. Phosphoinositide-3 kinase (PI3K)/Akt signaling plays a pivotal role in various stem cell systems, including the formation of embryonic germ (EG) cells from primordial germ cells and self-renewal of neural stem cells. Here, we show that myristoylated, active form of Akt (myr-Akt) maintained the undifferentiated phenotypes in mouse ES cells without the addition of leukemia inhibitory factor (LIF). The effects of myr-Akt were reversible, because LIF dependence and pluripotent differentiation activity were restored by the deletion of myr-Akt. In addition, myr-Akt-Mer fusion protein, whose enzymatic activity is controlled by 4-hydroxy-tamoxifen, also maintained the pluripotency of not only mouse but also cynomolgus monkey ES cells. These results clearly demonstrate that Akt signaling sufficiently maintains pluripotency in mouse and primate ES cells, and support the notion that PI3K/Akt signaling axis regulates 'stemness' in a broad spectrum of stem cell systems.

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Efficient gene transfer of a simian immuno‐deficiency viral vector into cardiomyocytes derived from primate embryonic stem cells

Abstract: A lentiviral vector system based on SIV represents a useful vehicle for genetic modification of cardiomyocytes derived from primate ES cells, and can extend the application of primate ES cells to gene therapy.

Cited by 9 publications

References 31 publications

Gene therapy to inhibit xenoantibody production using lentiviral vectors in non-human primates

Gene therapy to inhibit xenoantibody production using lentiviral vectors in non-human primates

N-Myc Down-regulated Gene 1 Modulates the Response of Term Human Trophoblasts to Hypoxic Injury

Activation of Akt signaling is sufficient to maintain pluripotency in mouse and primate embryonic stem cells

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