Autophagy is essential for maintaining the growth of a human (mini-)organ: Evidence from scalp hair follicle organ culture

After years of massive growth human scalp HFs spontaneously enter into a rapid, apoptosis-driven organ involution process, orchestrated by a yet insufficiently understood organ-intrinsic “hair cycle clock”. Even after being removed from the body, human follicles maintain in vivo-like characteristics and spontaneously run through a fundamental organ remodeling process traversing through a stage of growth (anagen) and destruction (catagen). Exploiting this unique remodeling (mini-)organ, we unveil a crucial new role of autophagy in the growth of human hair follicles. Indeed, we present the first evidence that anagen hair matrix keratinocytes exhibit an active autophagic flux ex vivo, which is altered after the transition to catagen. Since genetic inhibition of follicular autophagy induces premature catagen and enhances hair matrix keratinocyte apoptosis, autophagic flux in the anagen hair matrix appears to be important for the maintenance of this stage. Indeed, the principal ingredients of a product used to treat hair loss induces autophagy in organ-cultured human scalp HFs and promotes anagen. We propose here that organ-cultured human hair follicle are a suitable (mini−)organ system to study both the role of autophagy in human physiology ex vivo and to test candidate agents that modulate autophagy in a therapeutically desired manner under clinically relevant conditions.