Neural Stem Cells Secrete Factors That Promote Auditory Cell Proliferation Via a Leukemia Inhibitory Factor Signaling Pathway

The capacity for perpetual self-renewal is one of the main characteristics of stem cells. Little is known about the effect of embryonic neural stem cell (NSC)-secreted factors on auditory cell proliferation in vitro. In the present work, two auditory cell types were cultured in the presence of NSC-secreted molecules and were evaluated in vitro. Our results demonstrated that both cell viability and cell proliferation were significantly enhanced upon treatment with NSC conditioned medium, which contains significantly elevated levels of leukemia inhibitory factor (LIF) secreted by NSCs. The NSC conditioned medium not only activated the expression of leukemia inhibitory factor receptor in House Ear Institute-organ of Corti 1 cells but also up-regulated the LIE downstream signal transducers and activators of transcription (STAT) 1 and STAT3. Blocking either the LIF signaling pathway with neutralizing antibodies or the downstream Janus kinase (JAK)/STAT pathway with JAK2 inhibitor AG490 resulted in a dose-dependent inhibition of cell proliferation, suggesting that NSC-secreted molecules promote auditory cell survival via the regulatory LIF/JAK/STAT signaling pathway. (C) 2010 Wiley-Liss, Inc.