Derivation of germline competent embryonic stem cells with a combination of interleukin-6 and soluble interleukin-6 receptor.

In this report we document the derivation of pluripotential embryonic stem (ES) cells in the absence of a feeder layer by supplementation of culture media with either ciliary neurotrophic factor or oncostatin M, or with a combination of interleukin-6 (IL-6) plus soluble interleukin-6 receptor (sIL-6R). These factors all activate gp130-associated signaling processes, as does the previously characterized ES cell maintenance factor Differentiation Inhibiting Activity (Leukemia Inhibitory Factor). In particular, the IL-6/sIL-6R complex is thought to act exclusively through gp130. All ES cell lines derived using IL-6/sIL-6R contributed extensively to chimeras and were transmitted through the germline at high frequency. These findings point to a pivotal role for gp130 in ES cell propagation and may be relevant to attempts to derive ES cells from species other than mouse.