Here researchers show, once more, that the process of creating a line of induced pluripotent stem cells from ordinary cells and then differentiating the pluripotent cells back into the original cell types will repair and reverse measures of cell damage along the way. It makes sense that mechanisms of this nature must exist somewhere in the cellular repertoire, since parents are old but children are young: an embryo undergos a period of intense repair and restoration very early in its development process.
Now that numerous research teams having confirmed this aspect of induced pluripotency and are cataloging the details, the real question is what can be done with this? Producing less damaged patient-matched cells for cell therapies in the old is one immediate possibility, but evidence to date suggests that the problem is the tissue environment as much as the cells - even young and undamaged cells struggle once introduced back into old tissues. So how best to use damage repair via induced pluripotency in therapies remains an open question, I think:
Most neurodegenerative diseases are late-onset and aging-related, and no effective treatments have been developed. The successful generation of induced pluripotent stem cells (iPSCs) and the direct conversion of neurons from patients' specific somatic cells have offered cell resources for disease modeling and potential cell transplantation therapy. However, to date no systematic studies have investigated which approach is more suitable for future cell therapy. Here, using the two approaches mentioned above in parallel we successfully obtained functional neurons from tail-tip fibroblasts (TTFs) of a 1-year-old mouse, which were characterized by specialized morphologies, neuronal marker expressions and electrophysiological properties.Genome-wide expression analysis revealed that a set of genes related to the stress response and DNA damage were expressed at a much higher level in iNs than in diNs derived from 1-year-old TTFs. Subsequently, significant decreases in mitochondrial dysfunction and DNA damage were observed in diNs compared with iNs derived from aged TTFs. Moreover, the levels of epigenetic markers such as 5hmC, H3K4me3, H3K9me3 and H3K27me3 in iNs were more similar to those in the old TTFs compared with those in diNs, indicating that the iNs converted directly from TTFs may retain some residual epigenetic memories. By contrast, reprogramming to iPSCs not only rejuvenated the cell stages but also erased such epigenetic memories obtained along the aging process. Taken together, the results of our study are instructive and meaningful for future clinical applications.
Link: http://dx.doi.org/10...9/scd.2015.0137
View the full article at FightAging
