Another Indication that Age is a Low Barrier to Cell Therapies

There have been a number of research results in the past year or two that suggest the barriers posed by age to the production of patient-specific cells suitable for stem cell therapies are lower than first thought. Several research groups have obtained useful cells from old patients, showing that age-related damage to patient cells is no barrier to reprogramming them - indeed, the reprogramming appears to repair many types of damage. Here is another such result: "Somatic cells reprogrammed into induced pluripotent stem cells (iPSCs) acquire features of human embryonic stem cells (hESCs) and thus represent a promising source for cellular therapy of debilitating diseases, such as age-related disorders. ... Aged somatic cells might possess high susceptibility to nuclear and mitochondrial genome instability. Hence, concerns over the [potential of reprogrammed cells to spawn cancer] due to the lack of genomic integrity may hinder the applicability of iPSC-based therapies for age-associated conditions. ... Four iPSC lines were generated from dermal fibroblasts derived from an 84-year-old woman, representing the oldest human donor so far reprogrammed to pluripotency. ... all aged-iPSCs were able to differentiate into neurons, re-establish telomerase activity, and reconfigure mitochondrial ultra-structure and functionality to a hESC-like state. Importantly, aged-iPSCs exhibited high sensitivity to drug-induced apoptosis and low levels of oxidative stress and DNA damage, in a similar fashion as iPSCs derived from young donors and hESCs. Thus, the occurrence of chromosomal abnormalities within aged reprogrammed cells might not be sufficient to over-ride the cellular surveillance machinery and induce malignant transformation through the alteration of mitochondrial-associated cell death. Taken together, we unveiled that cellular reprogramming is capable of reversing aging-related features in somatic cells from a very old subject, despite the presence of genomic alterations."

Link: http://dx.doi.org/10.1371/journal.pone.0027352

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