US researchers have devised a process to reprogramme mature cells into a stem-cell-like state that can be accelerated.
The findings, published in Nature, shed light on the processes underlying how induced pluripotent stem (iPS) cells are produced. These iPS cells are the ethical ‘embryo-free’ alternative to stem cells and are claimed to hold great promise for regenerative medicine.
The researchers studied the ability of mature immune cells to generate iPS cells upon continued exposure to four previously defined reprogramming factors - achieved by overexpression of genes coding Oct4, Sox2, Klf4 and c-Myc transcription factors. Nearly all of the mouse donor cells were able to form iPS cells, although they took different lengths of time to do so.
The results indicate that reprogramming is not the sole preserve of an elite subset of cells, but a continuous, essentially random process that almost any cell can undergo given the right conditions.
Critically, the team showed that there are two methods whereby the process can be accelerated. The first depends on the rate at which the donor cells divide, which which involves inhibition of the p53/p21 pathway or overexpression of Lin28 genes. In contrast, the other method that does not depend on cell division rate involves Nanog overexpression. Therefore, the results also establish a new model in which cell division number, rather than the absolute time of reprogramming factor expression, drives the kinetics of iPS cell production.
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