Showing papers by "Shin-ichi Muramatsu published in 2003"

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

Abstract: Background Embryonic stem (ES) cells continually proliferate and can generate large numbers of differentiated cells. Genetic manipulation of transplantable cells derived from primate ES cells offers considerable potential for development research and regenerative cell therapy. However, protocols for efficient gene transfer into primate ES-cell-derived cells have not yet been established. Methods Spontaneously contracting areas were derived from cynomolgus monkey ES cells. Features of cardiomyocytes in the area were analyzed according to gene expression (RT-PCR), morphology (immunostaining and electron microscopy), and function (intracellular calcium transience). Beating cells were transduced using a simian immunodeficiency virus (SIV) vector expressing enhanced green fluorescence protein (EGFP), then transplanted into ischemic rat myocardium. Results Beating cells derived from monkey ES cells displayed gene expression, ultrastructural and functional properties of early-stage cardiomyocytes. Highly efficient (97% cardiac phenotype) and stable transduction of these ES-cell-derived cardiomyocytes was achieved using SIV vector without altering contractile function. In addition, transduced cardiomyocytes survived in the myocardium of a rat myocardial infarction model. Conclusions 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. Copyright © 2003 John Wiley & Sons, Ltd.

Adeno-associated viral vectors for Parkinson's disease.

Abstract: Publisher Summary This chapter presents recombinant adeno-associated viral (rAAV) vector that represents one of the most powerful vehicles for delivering therapeutic genes into mammalian brains. In rodents and nonhuman primates, a substantial number of striatal neurons can be transduced with high titer rAAV vectors through simple stereotaxic injection. Although chromosomal rearrangements in association with integration of rAAV have been indicated in a transformed cell line, the safety and potential efficacy of rAAV vectors have been demonstrated both in animal models of several diseases and in clinical trials on patients with hemophilia. Recent advances in the field of neural or embryonic stem cell research have raised the hope of cell replacement as an alternative therapy for Parkinson's disease (PD). The significant functional recovery achieved with the triple transduction method in the primate model provides an optimistic outlook for gene therapy treatment of PD. Gene therapy using rAAV vectors is now not merely an experimental strategy, but offers a novel and apparently feasible protocol for the treatment of PD.