Problem: embryonic stem cell lines vary & iPS lines too

Finally I started to digest all the articles (usually on the streetcar on my way to work and home) from the recent Nature Insight: Regenerative Medicine and I try to pick up some stories for you (& interesting enough for me) from that, in case you are not lucky enough to have an available copy.

For clinicians, the lack of gold standard embryonic stem cell lines with the measurably same regeneration potential will be a huge technological problem later while this variability is an interesting basic science problem today.

Kenneth R. Chien: Regenerative medicine and human models of human disease

A central challenge to the development of human stem-cell-based models of disease lies in the need to isolate and expand rare cell populations reproducibly and then to fully differentiate enough of the cells of interest. In this regard, one of the main obstacles to establishing human ES-cell-based models is that ES cell lines vary. All lines do not have the same potential to differentiate into cells of a particular lineage, most probably as a result of inherent epigenetic, genetic and developmental differences at the time of their isolation. For example, a study of 17 independent human ES cell lines showed that 7 of these lines had little or no capacity to enter the cardiovascular lineage, and the level of cardiovascular markers expressed by 2 of the 17 cell lines was an order of magnitude or more higher than that of these 7 lines. Similar variability between human ES cell lines was observed for entry to the pancreatic lineage, and cell lines that were optimal for generating cells of endodermal lineages were extremely poor for generating mesodermal lineage cells in many cases. Thus, new human ES cell lines that are optimal for generating specific lineages of interest need to be produced. In addition, iPS cell lines might be similarly variable. Even iPS cell lines derived from a single stock of patient-specific fibroblasts are likely to vary extensively, potentially making comparisons between disease-specific cell lines and normal cell lines challenging. It will therefore also be crucial to compare the proportion of highly purified, well-characterized differentiated cells of each lineage that can be obtained from various ES cell lines to set a baseline for variability.

The cited article: Osafune et al: Marked differences in differentiation propensity among human embryonic stem cell lines

Nature Biotechnology 26, 313 – 315

Abstract:

The differentiation potential of 17 human embryonic stem (hES) cell lines was compared. Some lines exhibit a marked propensity to differentiate into specific lineages, often with >100-fold differences in lineage-specific gene expression. For example, HUES 8 is best for pancreatic differentiation and HUES 3 for cardiomyocyte generation. These non-trivial differences in developmental potential among hES cell lines point to the importance of screening and deriving lines for lineage-specific differentiation.