Abstract:
:With the identification of stem cell plasticity several years ago, multiple reports raised hopes that tissue repair by stem cell transplantation could be within reach in the near future. Krause et al reported that a single purified hematopoietic stem cell not only repopulated the bone marrow of a host animal, but also integrated into unrelated tissues. Lagasse et al demonstrated that in a genetic model of liver disease, purified hematopoietic stem cells can give rise to hepatocytes and rescue fatal liver damage. More recent work by Jiang et al demonstrated that cultured cells can retain their stem cell potential. There are a number of possible mechanisms that could explain these phenomena, and recent experiments have raised controversy about which mechanism is prevalent. One possibility is transdifferentiation of a committed cell directly into another cell type as a response to environmental cues. Transdifferentiation has been shown mainly in vitro, but some in vivo data also support this mechanism. Direct transdifferentiation would clinically be limited by the number of cells that can be introduced into an organ without removal of resident cells. If bone marrow cells could on the other hand give rise to stem cells of another tissue, then they could in theory repopulate whole organs from a few starting cells. This model of dedifferentiation is consistent with recent data from animal models. Genetic analysis of cells of donor origin in vivo and in vitro has brought to light another possible mechanism. The fusion of host and donor cells can give rise to mature tissue cells without trans- or dedifferentiation. The resulting heterokaryons are able to cure a lethal genetic defect and do not seem to be prone to give rise to cancer. All these models will clinically face the problem of accessibility of healthy primary cells for transplantation. This underlines the importance of the recent identification of a population of mesenchymal stem cells (MSCs) with stem cell properties similar to embryonic stem (ES) cells. These cells can be cultured and expanded in vitro without losing their stem cell potential making them an attractive target for cell therapy. Finally, it is still not clear if stem cells for various tissues are present in peripheral blood, or bone marrow and thus can be directly purified from these sources. Identification of putative tissue stem cells would be necessary before purification strategies can be devised. In this review, we discuss the evidence for these models, and the conflicting results obtained to date.
journal_name
Gene Therjournal_title
Gene therapyauthors
Kashofer K,Bonnet Ddoi
10.1038/sj.gt.3302571subject
Has Abstractpub_date
2005-08-01 00:00:00pages
1229-34issue
16eissn
0969-7128issn
1476-5462pii
3302571journal_volume
12pub_type
杂志文章,评审相关文献
GENE THERAPY文献大全abstract::The oncotropic phenotypes of several viruses correlate with tumor-associated deficiencies within interferon (IFN) signaling pathways. This observation formed the conceptual basis for developing oncolytic viruses deleted for viral proteins that inhibit the host IFN-dependent antiviral response, such as herpes simplex v...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2009.68
更新日期:2009-09-01 00:00:00
abstract::Hepatic fibrosis is a common outcome of chronic liver diseases. In schistosomiasis, chronic parasite egg-induced granuloma formation can lead to fibrosis, which is immunologically characterized by the dominant Th2 response. Recently, it has been shown that gene therapy is an attractive approach for the treatment of he...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301524
更新日期:2001-09-01 00:00:00
abstract::Although particle-mediated gene transfer using gene gun technology has been applied for gene transfer into epidermis, applications of this technology to visceral tissues have not been well investigated. Although all helium gas-driven gene gun instruments have used macrocarriers to discharge DNA-coated microprojectiles...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301192
更新日期:2000-07-01 00:00:00
abstract::Low levels of expression in haemopoietic cells of the DNA repair protein O6-alkylguanine-DNA alkyltransferase (A Tase), is associated with the dose-limiting sensitivity of these cells to the chemotherapeutic chloroethylating and related methylating agents. Thus, the use of agents which deplete ATase such as O6-benzylg...
journal_title:Gene therapy
pub_type: 杂志文章
doi:
更新日期:1996-10-01 00:00:00
abstract::Adenoviral gene transfer to hematopoietic stem cells (HSCs)/progenitors would provide a new approach to the treatment of hematopoietic diseases and study of the hematopoietic system. We have previously reported that an adenovirus (Ad) vector composed of whole Ad serotype 35 (Ad35), which belongs to subgroup B, shows e...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302562
更新日期:2005-10-01 00:00:00
abstract::This study uses a novel approach to gene therapy in which plasmid DNA is targeted to the pancreas in vivo using ultrasound-targeted microbubble destruction (UTMD) to achieve islet regeneration. Intravenous microbubbles carrying plasmids are destroyed within the pancreatic microcirculation by ultrasound, achieving loca...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2010.85
更新日期:2010-11-01 00:00:00
abstract::Dendritic cell (DC)-based vaccine approaches are being actively evaluated for developing immunotherapeutic agents against cancers. In this study, we investigated the use of engineered DCs expressing transgenic tumor-associated antigen hgp100 and the regulatory cytokine interleukin-21, namely DC-hgp100/mIL-21, as a the...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2014.12
更新日期:2014-05-01 00:00:00
abstract::Adeno-associated virus (AAV) derived vectors are considered highly eligible vehicles for human gene therapy. Not only do they possess many great potential for clinical applications due to their wide range of tissue targets but also their excellent preclinical safety profile makes them particularly suitable candidates ...
journal_title:Gene therapy
pub_type: 杂志文章,评审
doi:10.1038/sj.gt.3302724
更新日期:2006-05-01 00:00:00
abstract::Phase 1 clinical trials of liposome-mediated gene therapy for cystic fibrosis have been completed and in all cases the expression level achieved has been low and transient. Clearly, improvements in the efficiency of gene transfer are required. It is now being recognised that delivery of high doses of DNA/liposomes to ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301097
更新日期:2000-03-01 00:00:00
abstract::Complexes of DNA and cationic lipid offer potential advantages for gene transfer to airway epithelia. However, we found that application of DNA-lipid (DMRIE-DOPE) complexes to primary cultures of human ciliated airway epithelia or explants of rabbit trachea generated only low levels of gene transfer. In contrast, when...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300524
更新日期:1997-11-01 00:00:00
abstract::Viral gene vectors often rely on packaging cell lines, which provide the necessary factors in trans for the formation of virus-like particles. Previously, we reported on a first-generation packaging cell line for gene vectors, which are based on the B-lymphotropic Epstein-Barr virus (EBV), a human gamma-herpesvirus. T...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302714
更新日期:2006-05-01 00:00:00
abstract::The insertion of suicide genes in donor T lymphocytes constitutes the basis of new approaches aiming at the treatment of the graft-versus-host disease (GVHD), a frequent complication in recipients of allogeneic haematopoietic grafts. In this study we investigated the impact that the ex vivo manipulation required for t...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302188
更新日期:2004-03-01 00:00:00
abstract::The prognosis of pancreatic adenocarcinoma is poor and current treatment ineffective. A novel treatment strategy is described here using a mouse model system for pancreatic cancer. Cells that have been genetically modified to express the cytochrome P450 2B1 enzyme are encapsulated in cellulose sulphate and implanted i...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300671
更新日期:1998-08-01 00:00:00
abstract::Cationic lipid-DNA complexes (lipoplexes) have been widely used as gene transfer vectors which avoid the adverse immunogenicity and potential for viraemia of viral vectors. With the long-term aim of gene transfer into skeletal muscle in vivo, we describe a direct in vitro comparison of two commercially available catio...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300604
更新日期:1998-04-01 00:00:00
abstract::Autonomous parvoviruses are small, single strand DNA viruses which preferentially replicate in transformed and tumor cells, causing cell death by expression of the cytotoxic nonstructural protein, NS1. Several parvoviruses of the rodent group, including LuIII, efficiently infect human transformed cell lines. The poten...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300832
更新日期:1999-03-01 00:00:00
abstract::Various methods for determining the expression of the beta-galactosidase (beta-gal) gene after retroviral transduction were compared as a means to assess retroviral titre. To allow better comparison, different retroviral vectors were constructed carrying two mutants of the green fluorescent protein and assessed as sen...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300519
更新日期:1997-11-01 00:00:00
abstract::Delivery of a normal copy of CFTR cDNA to airway epithelia may provide a novel treatment for cystic fibrosis lung disease. Unfortunately, current vectors are inefficient because of limited binding to the apical surface of airway epithelia. We recently reported that incorporation of adenovirus in a calcium phosphate co...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301020
更新日期:1999-11-01 00:00:00
abstract::To test whether fast-acting, self-complimentary (sc), adeno-associated virus-mediated RPE65 expression prevents cone degeneration and/or restores cone function, we studied two mouse lines: the Rpe65-deficient rd12 mouse and the Rpe65-deficient, rhodopsin null ('that is, cone function-only') Rpe65(-/-)::Rho(-/-) mouse....
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2010.29
更新日期:2010-07-01 00:00:00
abstract::Current experimental gene therapy approaches for Parkinson's disease (PD) and dementia with Lewy bodies (DLB) include the use of viral vectors expressing antiapoptosis genes, neurotrophic factors and dopaminergic system enzymes. However, since increasing evidence favors a role for alpha-synuclein accumulation in the p...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302349
更新日期:2004-12-01 00:00:00
abstract::The mechanism whereby cationic lipids destabilize cell membranes to facilitate the intracellular delivery of macromolecules such as plasmid DNA or antisense oligonucleotides is not well understood. Here, we show that cationic lipids can destabilize lipid bilayers by promoting the formation of nonbilayer lipid structur...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301506
更新日期:2001-08-01 00:00:00
abstract::The potential of gene therapy for treatment of lung disease remains unrealised. Early model systems often resulted in promising efficiency of gene transfer, only to prove irreproducible in the clinic. While problems such as induction of host immune responses and duration of expression also need to be addressed, it is ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301146
更新日期:2000-04-01 00:00:00
abstract::Attempts have been made to use various forms of cellular vectors to deliver therapeutic genes to diseased tissues like malignant tumours. However, this approach has proved problematic due to the poor uptake of these vectors by the target tissue. We have devised a novel way of using magnetic nanoparticles (MNPs) to enh...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2008.57
更新日期:2008-06-01 00:00:00
abstract::Transplantation faces several major obstacles that could be overcome by expression of immunomodulatory proteins through application of gene therapy techniques. Gene therapy strategies to prolong graft survival involve gene transfer of immunosuppressive or graft-protecting molecules. Very promising results have been ob...
journal_title:Gene therapy
pub_type: 杂志文章,评审
doi:10.1038/sj.gt.3301083
更新日期:2000-01-01 00:00:00
abstract::Cellular immunity against cancer can be achieved with viral vector- and DNA-based immunizations. In preclinical studies, cancer vaccines are very potent, but in clinical trials these potencies are not achieved yet. Thus, a rational approach to improve cancer vaccines is warranted. We previously demonstrated that the r...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2015.24
更新日期:2015-07-01 00:00:00
abstract::Genetic engineering of T lymphocytes for adoptive clinical immunotherapy calls for efficient gene transduction methods. Therefore, a transient retroviral gene transduction system 'STITCH' was developed comprising pSTITCH retroviral vector encoding the transgene, plasmids encoding Moloney murine leukemia virus gag/pol ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300696
更新日期:1998-09-01 00:00:00
abstract::In high-risk patients, the ideal cardiovascular gene therapy requires a strategy that provides long-term protection of myocardium against episodes of ischemic/reperfusion injury. We report the development of an efficient, long-lasting pre-emptive gene therapy strategy in a rat model of ischemic-reperfusion (I/R) injur...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302250
更新日期:2004-06-01 00:00:00
abstract::We have previously established a stable HIV-1 packaging cell line, psi 422, which yielded high titers of an HIV-1 vector capable of efficiently transducing CD4+ cells. In order to increase the safety of this gene delivery system, we have now replaced the HIV-1 vector with an HIV-2 vector to abolish any risk of homolog...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300563
更新日期:1998-01-01 00:00:00
abstract::A highly desirable feature for an human immunodeficiency virus type 1 (HIV-1) vaccine is the ability to induce broadly reactive anti-envelope antibodies that can neutralize primary HIV-1 isolates. Two immunizations with an HIV-1 envelope-encoding plasmid together with recombinant granulocyte-macrophage colony-stimulat...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302275
更新日期:2004-07-01 00:00:00
abstract::Substantial advances in our understanding of lentivirus lifecycles and their various constituent proteins have permitted the bioengineering of lentiviral vectors now considered safe enough for clinical trials for both lethal and non-lethal diseases. They possess distinct properties that make them particularly suitable...
journal_title:Gene therapy
pub_type: 杂志文章,评审
doi:10.1038/gt.2011.153
更新日期:2012-02-01 00:00:00
abstract::Gyrate atrophy (GA) of the choroid and retina is an autosomal recessive chorioretinal degeneration, caused by deficiency of the mitochondrial matrix enzyme ornithine-delta-aminotransferase (OAT). This deficiency results in the accumulation of ornithine in the body fluids and leads to hyperornithinemia. Although the cl...
journal_title:Gene therapy
pub_type: 杂志文章
doi:
更新日期:1995-01-01 00:00:00