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| RIKEN Press Release | February 4, 2008 |
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Clean stem cells light the wayA visionary method for coaxing stem cells into becoming uncontaminated light-sensing cells could lead to transplantation to restore eyesight. | |
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People suffering from various ocular diseases received some welcome news in the Feb. 3, 2008, issue of Nature Biotechnology - scientists from RIKEN's Center for Developmental Biology, Kyoto University Hospital and other Japanese research institutes report a breakthrough in retinal cell generation that promises to significantly advance the development of transplantation therapies for blindness. The team, led by Masayo Takahashi, is the first to successfully propagate specialized human 'photoreceptor,' or light-sensing cells, in defined laboratory conditions that are completely free of animal materials. The retina, the thin layer of nerve cells that interfaces between the outside world and the brain, is often described - quite accurately - as the functional equivalent, in the eye, of a camera's film. Much of the rest of the eye is designed to mechanically focus light onto the retina. Light reaching the retina activates photoreceptor cells (rods and cones) to create chemically-mediated excitation patterns, which in turn are converted into electrical signals that are transmitted, via the optic nerve, to the brain for processing. The photoreceptors depend on special support cells, the retinal pigmented epithelial (RPE) cells, for maintenance, nourishment and recycling of the proteins critical for vision. Unfortunately, retinal tissues, which are fragile and prone to degeneration, do not regenerate in the adult mammal. Many ocular problems can be remedied via mechanical or surgical interventions but many others, such as retinitis pigmentosa, cone dystrophy and age-related macular degeneration, involve problems with retinal cells and had, until recently, been regarded as incurable forms of blindness. Hence, a promising therapeutic modality in this field focuses on transplanting laboratory-generated functional retinal cells to replace the lost or dysfunctional photoreceptors and/or RPE cells. Indeed, much success has already been achieved in animal models and a clinical trial for retinitis pigmentosa using fetal retinas is actually in progress. Nevertheless, fetal tissues involve ethical issues, problematic supplies and relatively low transplantation success rates, which scientists hope to avoid by transplanting more mature photoreceptor cells. Takahasi's team had already experimentally determined that ES cells represent the best source of photoreceptor and RPE cells. However, a major disadvantage of standard human ES cell culture techniques is the need for mouse 'feeder' cells that supply a multitude of chemicals that nourish and support the stems cells, allowing them to survive, grow, and divide in culture. Such practices risk 'xenogenic' contamination, i.e. stem cells become adulterated with mouse proteins and carry these animal-signature chemicals on their surfaces - a guaranteed recipe for rejection when transplanted into human patients. Another problem specific to retinal cell generation is the need to co-culture ES cells with embryonic retinal tissues to drive ES differentiation to the retinal cell lines. To overcome these cell culture obstacles, Takahashi's team developed a potent cocktail of chemicals that not only allowed human ES cells to grow absent animal serum or feeder cells but also induced these ES cells to differentiate into photoreceptor cells without the need for embryonic retinal tissues. This is the first efficient method for reliably generating retinal cells, and also worked with monkey and mouse ES cells. Some hurdles remain, particularly after transplantation, and more testing in animal models will be required. Nonetheless, Takahashi and colleagues are hopeful that the combined transplantation of photoreceptor and RPE cells will result in more effective and successful outcomes. This new procedure will doubtless dramatically improve our understanding of the eye and should also have many other applications, including in the exciting new area of inducing pluripotent stem cells from adult human cells. Is there a bright future for human ES-cell based transplantation therapies for retinal diseases? As the old maxim goes: seeing really is believing ...
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| RIKEN, one of Japan's leading research institutes, conducts basic and applied experimental research in a wide range of science and technology fields including physics, chemistry, medical science, biology and engineering. Initially established as a private research foundation in Tokyo in 1917, RIKEN became an independent administrative institution in 2003. For more information, visit www.riken.jp | |
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