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Registered User
Join Date: Aug 2009
Location: Trieste, Italy
Posts: 90
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Info on STEM CELLS from scientific source
First of all sorry, this post will be very long, maybe too much. Anyway it deals with scientific information on stem cells.
Since we are seeing a lot of information on stem cells from press release, web-sites, any other kind of source impossible to judge about quality and reliability, I would like to paste here some exctract of a review article published on the September 2008 (pretty recent, then) Cell and Tissue Research. Beisel K, Hansen L, Soukup G, Fritzsch B, Cell Tissue Res. 2008, 333(3):373-9. Regenerating cochlear hair cells: quo vadis stem cell Abstract: Many elderly people worldwide lose the neurosensory part of their ear and turn deaf. Cochlear implants to restore some hearing after neurosensory hearing loss are, at present, the only therapy for these people. In contrast to this therapy, replacement of hair cells via stem cell therapies holds the promise for a cure. We review here current insights into embryonic, adult, and inducible stem cells that might provide cells for seeding the cochlea with the hope of new hair cell formation. We propose a two-step approach using a first set of transcription factors to enhance the generation of inducible pluripotent stem (iPS) cells and a second set of factors to initiate the differentiation of hair cells. Recent evidence regarding ear development and stem cell research strongly suggest that microRNAs will be an important new regulatory factor in both iPS cell formation and differentiation to reprogram cells into hair cells. In addition, we highlight currently insurmountable obstacles to the successful transformation of stem cells into hair cell precursors and their injection into the cochlear canal to replace lost hair cells. I would like to put some exctract from the text. I cannot paste the whole article, since it is under copyright. I can have access to it from the library here at work, then I am authorized to read it. I can possibly send a copy to a few interested people. Otherwise you should try to get access to a copy of the journal at some public libraries. There are other, even more recent reviews on that, one is on Nature Neuroscience, but unfortunately I cannot get access to at the moment. It is TRUE that some successful experiments have been done on animal models: "Attempts at seeding the ear with pluripotent stem cells to form new hair cells or neurons are being pursued and have been successfully implemented in animal models for sensory neuron loss (Martinez-Monedero et al. 2006; Senn and Heller 2008)." Anyway, there is still a lot of work to be done, before being really able to restore a working tissue: "With our growing knowledge of the functional genomics of hair cell differentiation, we might soon be able to use regulatory genes for the transdifferentiation of supporting cells into hair cells (Raphael et al. 2007). However, the drawback to such an approach is that it would deplete our supply of supporting cells and cause structural disorganization within the cytoarchitecture of the organ of Corti (Fritzsch et al. 2006)." It is TRUE there are incouraging results on the HUMAN tissue, for regeneration of hairy cells. Many different strategies are under development and there are some incouraging results. Anyway there are still some study to do on the best source of stem cells to properly generate a correct organization of hearing tissue: "various neural tissues (Tamura et al. 2004; Tateya et al. 2003), or neurosensory precursors (Hu et al. 2005) have been tested for their capacity to develop into hair-cell-like cells and to survive when injected into the ear, generating a substantial body of literature indicating how best to implant cells for neuronal (Corrales et al. 2006; Martinez-Monedero et al. 2006; Tamura et al. 2004; Tateya et al. 2003; Ulfendahl et al. 2007) or sensory (Iguchi et al. 2004; Li et al. 2004; Naito et al. 2004; Nakagawa and Ito 2005) replacement. Overall, the data are encouraging as they indicate that the technical problem of how to implant properly primed precursors into the cochlea or modiolus for hair cell and sensory neuron replacement is solvable. The main obstacles seem to be the identification of a source that provides enough stem cells to allow such therapies to have a good chance of success." iPS cell type are among the most promising cell lines, anyway it must be noted that who think that there are no risk associated to the stem cell therapy should have a look here. The point is, among many issues, to instruct the undifferentiated stem cells to evolve into hairy cell tissue, but also to instruct them how and when to stop. The risk is tumor formation: "Despite this proof of principle, optimism should be restrained. Some problems that affect other potential therapeutic approaches with ES and AS cells similarly apply to iPS cells, for which the efficacy of the procedure and serious risk of tumor formation make iPS cells currently unsuitable for human trials (Holden and Vogel 2008)." A summary of the most important issues still to be tackled: "Initially, it is critical that we not only find a way to turn on proliferation, but that we also have a means to turn it off. Without adequate cell cycle control, any of the techniques discussed above have the risk of forming tumors. Furthermore, the cochlea is an enclosed space surrounded by bone, in which an inner ear tumor would very rapidly destroy the delicate organ and the adjacent facial nerve. This is the case for Schwannoma of the VIIIth nerve. Another critical issue for the restoration of hearing is the rebuilding of the appropriate cytoarchitecture required for the organization and polarization of the hair cells within the organ of Corti. Any perturbation in the cytoarchitecture of the organ of Corti almost always leads to hearing loss. In a properly functioning cochlea, the outer and inner hair cells are organized in a three-to-one radial configuration. Additionally, each individual hair cell has a polarity defined by placement of the kinocilium and stereocilia pattern on the apical surface. In order for the hair cells to be stimulated by sound waves in the basilar membrane, they must all align perpendicular to the long axis of the cochlea. Although we know that genes such as Foxg1 are involved in determining the number of rows of hair cells and the polarity of hair cells in the organ of Corti (Pauley et al. 2006), we do not yet have a firm grasp of the way in which these features are defined in the normal cochlea (Jones and Chen 2007). Likewise, the supporting cell distribution and differentiation is critical for hearing. [...] Although we have made major inroads with regards to our understanding of the molecular basis of innervation, we do not yet know the molecular basis for outer and inner hair-cell-specific innervation. Clearly, the organization of cochlear hair cells, Cell Tissue Res (2008) 333:373–379 377 supporting cells, and their innervation will be, at least in part, governed by their surroundings. We have yet to determine how much influence the infrastructure (such as placement of the spiral artery) and gene expression from non-sensory cells adjacent to the organ of Corti will have on the developing hair cells, should attempts at regeneration as outlined above prove successful." Ok, one year has passed since this review has been published, but if you search the data banks, no noticeable revolutionary finding has been published. We are proceeding fast on the route, but the route still appears to be pretty long... |
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