iPS cells take a beating

It sounded too good to be true – the addition of a handful of genes to an adult skin cell would transform it into a stem cell capable of being adapted into any tissue type.

The excitement at Shinya Yamanaka’s groundbreaking discovery was intense.  No more need for embryo-derived stem cells!  A new way to generate tissue matched cells to repair any damaged organ!  An effective in vitro screening technology for many serious conditions.  (gasp!)

However… recent work published in Nature and Cell Stem Cell by several groups, including Toronto’s own Andras Nagy, has shown that these induced pluripotent stem cells (iPS cells) carry a lot of baggage.  Genomic and epigenomic analyses have confirmed that the genome of these cells is pretty messed up.

You may say “cells maintained in culture for any length of time usually develop some genetic anomalies” – and you’d be right.  But iPS cells appear to have around 10 times the mutations of cultured fibroblasts (normal skin cells used to create iPS cells).

Worse still, regardless of the method used to generate them, much of the damage seen in iPS cells is located around areas of the genome that relate to cell division and the potential development of cancers.

With such a range of genetic defects, including copy number variation, SNPs, deletions and epigenetic control, can these cells be used a faithful surrogate for human tissues in lab studies?  Will these cells ever be stable enough to use therapeutically?

An analogy might be the difference between a fresh photograph and a 10^th generation photocopy – somewhat recognizable but not anywhere near as clear as the original.

The future development of the iPS cell field hinges on this important issue.

Read more:

• Hussein, S. M. et al. Nature 471, 58–62 (2011).
• Gore, A. et al. Nature 471, 63–67 (2011).
• Lister, R. et al. Nature 471, 68–73 (2011).
• Mayshar, Y. et al. Cell Stem Cell 7, 521–531 (2010).
• Laurent, L. C. et al. Cell Stem Cell 8, 106–118 (2011).