induced Pluripotent Stem cells from a 69 year old human: the hidden story?

The successful reprogramming (dedifferentiation) of differentiated human somatic cells into a pluripotent, embryonic stem cell-like state called induced pluripotent stem cells (iPS) using just 4 (and recently 3) introduced transcription factors is the biggest news of current stem cell biology. In the paper published in Cell by the Yamanaka group (Takahashi et al.) the iPS clones derived from the facial dermis of a 36-year-old Caucasian female were highlighted. Out of 50 000 retrovirally transduced fibroblasts 10 hES cell-like colonies were observed. But what I found really thought provoking (and poorly discussed in the blogosphere) is that with the same approach iPS cells were generated from the synovial tissue of a 69-year-old Caucasian male. Interestingly out of 50 000 modified cells 17 hES cell-like colonies were found. This finding could easily be relevant from a stem cell aging point of view.

During ageing there is an overall decline in tissue regenerative potential, but it is not clear whether it is due to the intrinsic exhaustion of the adult tissue stem cells or the diminished functionality of the stem cell niche or a change in the systemic milieu. Answers could be different - tissue by tissue.

But if a terminally differentiated connective tissue cell, like the synoviocyte above could be completely reprogrammed from a 69 year old, otherwise health individual into a pluripotent state….well it could it be interpreted as an argument against the cell-intrinsic genetic aging program in adult and aged connective tissues with some cautions.

Caution 1: What if the source of the iPS cells were not really terminally differentiated, but undifferentiated stem or progenitor cells coexisting in fibroblast culture. This problem has been discussed in the paper and forms the Achilles’ heel of it.

Caution 2: The reprogrammed iPS cells from an aged person are behaving the same way as the iPS cells from a younger person with no additional cellular aging characteristics.

As the critical tail of almost every peer-reviewed paper used to say: Further study is needed.

Here is the paragraph on the synoviocytes and the tables and figures are in the supplemental data.

First differentiated cell types in mammals are…

…blood cells, “generated in early-stage embryos, for instance in mice in the yolk sac at embryonic day (E) 7.0.-7.5, just 2 or 3 days after the undifferentiated conceptus implants in the uterus.” Source: Ueno-Weissman: Blood lines from embryo to adult Nature 446, 996-997 (26 April 2007)