Figure 9. Model for the role of exosomes as mediators of protection against hair cell death caused by ototoxic drugs.

Our data are consistent with a model in which heat stress induces HSP70 expression, predominately in supporting cells (Figure 1). Some of this HSP70 associates with exosomes (Table 1 and Figure 7, A and B) that are released into the extracellular environment (Figure 2A and Figure 5B). HSP70-carrying exosomes interact with TLR4 on the hair cell’s surface (Figure 8) to stimulate a pro-survival response (Figure 4, B and C, and Figure 5D). The significance of hair cell–derived exosomes (Figure 6, C–K) remains under investigation.