Abstract:
:Niemann-Pick type C (NP-C) disease is a neurodegenerative disorder characterized neuropathologically by ballooned neurons distended with lipid storage and widespread neuronal loss. Neural stem cells (NSC) derived from NP-C disease models have decreased ability for self-renewal and neuronal differentiation. Investigation of neurogenesis in the adult brain has suggested that NP-C disease can be overcome, or at least ameliorated, by the generation of new neurons. Bone-marrow-derived mesenchymal stem cells (BM-MSCs) are regarded as potential candidates for use in the treatment of neurodegenerative disorders because of their ability to promote neurogenesis. The underlying mechanisms of BM-MSC-induced promotion of neurogenesis, however, have not been resolved. The aim of the present study was to examine the mechanism of neurogenesis by BM-MSCs in NP-C disease. Coculture of embryonic NSCs from NP-C mice that exhibit impaired ability for self-renewal and decreased rates of neuronal differentiation with BM-MSCs resulted in an enhanced capacity for self-renewal and an increased ability for differentiation into neurons or oligodendrocytes. In addition, results of in vivo studies have demonstrated that transplantation of intracerebral BM-MSCs resulted in stimulated proliferation and neuronal differentiation of NSCs within the subventricular zone. Of particular interest, enhanced proliferation and neuronal differentiation of endogenous NP-C mouse NSCs showed an association with elevated release of the chemokine (C-C motif) ligand 2 (CCL2) from BM-MSCs. These effects suggest that soluble CCL2 derived from BM-MSCs can modulate endogenous NP-C NSCs, resulting in their improved proliferation and neuronal differentiation in mice.
journal_name
Hum Gene Therjournal_title
Human gene therapyauthors
Lee H,Kang JE,Lee JK,Bae JS,Jin HKdoi
10.1089/hum.2013.001subject
Has Abstractpub_date
2013-07-01 00:00:00pages
655-69issue
7eissn
1043-0342issn
1557-7422journal_volume
24pub_type
杂志文章abstract::Subcutaneous vaccination therapy with glioma cells, which are retrovirally transduced to secrete granulocyte-macrophage colony-stimulating factor (GM-CSF), has previously proven effective in C57BL/6 mice harboring intracerebral GL261 gliomas. However, clinical ex vivo gene therapy for human gliomas would be difficult,...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430340050057503
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abstract::Hereditary tyrosinemia type 1 (HT1) is an autosomal recessive disorder caused by deficiency of fumarylacetoacetate hydrolase (FAH). It has been previously shown that ex vivo hepatocyte-directed gene therapy using an integrating lentiviral vector to replace the defective Fah gene can cure liver disease in small- and la...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2017.252
更新日期:2018-11-01 00:00:00
abstract::The influence of serum on the production of retroviral vectors by the HT1080 human fibrosarcoma-derived packaging cell line FLYRD18 was investigated. A fourfold increase in virus titer was observed under serum-free conditions, as compared with medium supplemented with 10% fetal calf serum. A similar improvement was al...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430349950017329
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abstract::Establishing pharmacological parameters, such as efficacy, routes of administration, and toxicity, for recombinant adeno-associated virus (rAAV) vectors is a prerequisite for gaining acceptance for clinical applications. In fact, even a therapeutic window, that is, the dose range between therapeutic efficacy and toxic...
journal_title:Human gene therapy
pub_type: 杂志文章,评审
doi:10.1089/hum.2009.092
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abstract::Esophageal cancer is characterized by rapid clinical progression and poor prognosis, due to early-stage invasion of adjacent tissues and metastasis. Tissue factor pathway inhibitor-2 (TFPI-2) has been implicated as a metastasis-associated gene in many types of tumors. Here we describe the potential involvement of TFPI...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2008.129
更新日期:2009-01-01 00:00:00
abstract::A phase I clinical trial was conducted in which recombinant adenovirus containing the cystic fibrosis trans-membrane regulator (CFTR) (Ad2/CFTR) was administered by bronchoscopic instillation or aerosolization to the lungs of cystic fibrosis (CF) patients. In this paper, we evaluate the efficiency of Ad2/CFTR-mediated...
journal_title:Human gene therapy
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1089/104303401750298544
更新日期:2001-07-20 00:00:00
abstract::Point mutations in the dystrophin gene cause dystrophin deficiency and muscular dystrophy in the mdx mouse and a subset of patients with Duchenne muscular dystrophy. As an approach to gene therapy for muscular dystrophies due to point mutations, we have studied the ability of RNA-DNA chimeric oligonucleotides (chimera...
journal_title:Human gene therapy
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doi:10.1089/104303402317322276
更新日期:2002-04-10 00:00:00
abstract::La Crosse virus (LACV)-mediated encephalitis is the most frequently reported arboviral disease in the United States, but to date no vaccine against this virus is available. We have established a new animal model, genetically targeted mice lacking a functional interferon type I receptor (IFNAR-1). These mice show an ag...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430349950017653
更新日期:1999-07-01 00:00:00
abstract::This Phase I study, "Ribozyme Gene Therapy of HIV-1 Infection" (UCSD HSC #971072, FDA BB-IND 6405), is a prospective, open-label trial of infusion of autologous gene-altered cells into asymptomatic HIV-1 seropositive individuals. The objectives of this trial are to test the safety, feasibility, and potential efficacy ...
journal_title:Human gene therapy
pub_type: 临床试验,杂志文章
doi:10.1089/hum.1998.9.16-2407
更新日期:1998-11-01 00:00:00
abstract::Deficiency of glycogen branching enzyme (GBE) causes glycogen storage disease type IV (GSD IV), which is characterized by the accumulation of a less branched, poorly soluble form of glycogen called polyglucosan (PG) in multiple tissues. This study evaluates the efficacy of gene therapy with an adeno-associated viral (...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2016.099
更新日期:2017-03-01 00:00:00
abstract::Direct arterial gene transfer has been previously achieved using double-balloon catheters and perforated balloons, in most cases facilitated by the use of cationic liposomes or viral vectors. These gene delivery systems, however, have been compromised by issues relating to efficacy and/or safety, and furthermore requi...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1993.4.6-749
更新日期:1993-12-01 00:00:00
abstract::Guidelines for testing gene therapy products for ecotropic replication-competent retrovirus (Eco-RCR) have not been delineated as they have for amphotropic viruses. To evaluate biologic assays that can detect these viruses, we compared an S(+)/L(-) assay and a marker rescue assay designed specifically for Eco-RCR dete...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/104303402760293619
更新日期:2002-09-20 00:00:00
abstract::The ability to control proliferation of grafted cells in the heart and consequent graft size could dramatically improve the efficacy of cell therapies for cardiac repair. To achieve targeted graft cell proliferation, we created a chimeric receptor (F36Vfgfr-1) composed of a modified FK506-binding protein (F36V) fused ...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2006.161
更新日期:2007-05-01 00:00:00
abstract::Recombinant adeno-associated virus 2 (rAAV) vectors have been successfully used for sustained expression of therapeutic genes. The potential of using rAAV as a cancer vaccine vector and the impact of a bacterial plasmid adjuvant on this activity were investigated. C57BL/6 mice received a single intramuscular injection...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2004.15.856
更新日期:2004-09-01 00:00:00
abstract::Hepatic stellate cells (HSCs) are the primary cell type responsible for liver fibrogenesis. Transforming growth factor beta 1 (TGF-β1) and platelet-derived growth factor (PDGF) are key profibrotic cytokines that regulate HSC activation and proliferation with functional convergence. Dual RNA interference against their ...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2018.047
更新日期:2019-02-01 00:00:00
abstract::Pancreatic cancer is the fourth leading cause of cancer-related death in the United States, and even under optimal therapy these patients face a poor prognosis. Here we report a novel gene therapy-based strategy to battle this disease. We show that the majority of pancreatic tumors overexpress c-erb-B2, which therefor...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2009.083
更新日期:2010-02-01 00:00:00
abstract::Lentiviral vectors are promising tools for gene transfer into the central nervous system. We have characterized in detail transduction with human immunodeficiency virus type 1 (HIV-1)-derived vectors encoding enhanced green fluorescent protein (eGFP) in the adult mouse brain. Different brain regions such as the striat...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430340252899019
更新日期:2002-05-01 00:00:00
abstract::Despite efforts toward improvements in retrovirus-mediated gene transfer, stable high-level expression of a therapeutic gene in human hematopoietic stem cells remains a great challenge. We have evaluated the efficiency of different viral long terminal repeats (LTRs) in long-term expression of a transgene in vivo, usin...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/104303401450942
更新日期:2001-01-01 00:00:00
abstract::Therapeutic levels of expression of the beta-globin gene have been difficult to achieve with conventional retroviral vectors without the inclusion of DNase I-hypersensitive site (HS2, HS3, and HS4) enhancer elements. We generated recombinant adeno-associated viral (AAV) vectors carrying an antisickling human beta-glob...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2007.173
更新日期:2008-04-01 00:00:00
abstract::Adrenomedullin (AM) has been shown to protect against ischemia/reperfusion-induced myocardial infarction and apoptosis. In the present study, we examined the potential neuroprotective action of delayed AM gene transfer in cerebral ischemia. Three days after a 1-hr occlusion of the middle cerebral artery (MCAO), rats w...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2004.15.1243
更新日期:2004-12-01 00:00:00
abstract::Glaucoma, a group of optic neuropathies, is the leading cause of irreversible blindness. Neuronal apoptosis in glaucoma is primarily associated with high intraocular pressure caused by chronically impaired outflow of aqueous humor through the trabecular meshwork, a reticulum of mitotically inactive endothelial-like ce...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430340152677449
更新日期:2001-11-20 00:00:00
abstract::Abstract Our studies have shown that coinjection of conventional single-stranded adeno-associated virus 2 (ssAAV2) vectors carrying the enhanced green fluorescent protein (EGFP) gene with self-complementary (sc) AAV2-T cell protein tyrosine phosphatase (TC-PTP) and scAAV2-protein phosphatase-5 (PP5) vectors resulted i...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2009.100
更新日期:2010-03-01 00:00:00
abstract::The hepatocarcinoma-intestine-pancreas (HIP) gene, also called pancreatitis-associated protein-1 (PAP1) or Reg IIIalpha, is activated in most human hepatocellular carcinomas (HCCs) but not in normal liver, which suggests that HIP regulatory sequence could be used as efficient liver tumor-specific promoters to express ...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2007.153
更新日期:2008-09-01 00:00:00
abstract::The utility of first-generation adenovirus vectors for long-term gene transfer in humans is limited by preexisting antiadenoviral immunity. We demonstrate here that new-generation high-capacity adenovirus vectors (HC-Ads) can efficiently transduce the brain and mediate stable transgene expression for at least 2 months...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/104303401750148829
更新日期:2001-05-01 00:00:00
abstract::Leukocyte adhesion deficiency type I (LAD-I) is a primary immunodeficiency caused by mutations in the ITGB2 gene and is characterized by recurrent and life-threatening bacterial infections. These mutations lead to defective or absent expression of β2 integrins on the leukocyte surface, compromising adhesion and extrav...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2016.016
更新日期:2016-09-01 00:00:00
abstract::Twenty-eight patients with advanced neovascular age-related macular degeneration (AMD) were given a single intravitreous injection of an E1-, partial E3-, E4-deleted adenoviral vector expressing human pigment epithelium- derived factor (AdPEDF.11). Doses ranging from 10(6) to 10(9.5) particle units (PU) were investiga...
journal_title:Human gene therapy
pub_type: 杂志文章,多中心研究
doi:10.1089/hum.2006.17.167
更新日期:2006-02-01 00:00:00
abstract::We report on an antitumor treatment involving electrogene therapy (EGT), a newly developed in vivo gene transfer method using electroporation. We carried out in vivo EGT in a subcutaneous model of CT26 colon carcinoma cells, using plasmid DNAs encoding interleukin 12 (IL-12) subunits. For this purpose, we developed tw...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/104303401750270922
更新日期:2001-07-01 00:00:00
abstract::We report a novel method for targeting adenovirus-mediated gene delivery. By irradiating mammalian cells prior to adenoviral transduction, adenoviral gene transfer is greatly improved and the adenoviral genome integrates into cellular DNA. In this work, human and rodent cell lines were irradiated and subsequently tran...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1997.8.9-1025
更新日期:1997-06-10 00:00:00
abstract::Vectors derived from the human parvovirus AAV-2 (adeno-associated virus type 2) are among the most promising gene delivery vehicles currently being developed. These vectors are not only capable of transducing a large variety of human cell types in vitro and in vivo, but in immunocompetent animal models can establish l...
journal_title:Human gene therapy
pub_type: 杂志文章,评审
doi:10.1089/10430349950016799
更新日期:1999-10-10 00:00:00
abstract::MDA-MB-231, an HLA-A2(+), HER2/neu(+) allogeneic breast cancer cell line genetically modified to express the costimulatory molecule CD80 (B7-1), was used to vaccinate 30 women with previously treated stage IV breast cancer. Expression of CD80 conferred the ability to deliver a costimulatory signal and thereby improved...
journal_title:Human gene therapy
pub_type: 临床试验,杂志文章
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更新日期:2003-07-20 00:00:00