The inability to generate fully undifferentiated human induced pluripotent stem cells in vitro has dogged the development of stem cell-based platforms because the residual lineage bias of the cells most likely contributes to the inefficiency and inconsistency of current differentiation protocols. An Israeli team thinks it has solved the problem with the optimization of a small molecule and cytokine cocktail capable of maintaining human cells in a more fully undifferentiated state.1
The group expects that the naïve cells will be useful in generating somatic cells for research and clinical applications and for creating new animal models, although it still remains unclear whether the cells provide an advantage over conventionally derived induced pluripotent stem (iPS) cells.
In vitro, human iPS cells have been shown to be rather heterogeneous and to exhibit varying residual lineage characteristics-even when taken from the same patient.2 Residual lineage bias of iPS cells is reflected in DNA methylation patterns, transcriptional profiles with upregulated lineage commitment genes and X-chromosome inactivation.3,4
These varying genetic and epigenetic properties of iPS cell lines most likely are the reason why existing protocols for their differentiation into somatic lineages can be inefficient and inconsistent.
In addition, and although human pluripotent stem cells, albeit of limited stability, have been generated in a primed state in vitro using transgene expression, mouse pluripotent stem cells