Human hair follicle equivalents in vitro for transplantation and chip-based substance testing

Introduction The ability to create an organoid, the smallest functional unit of an organ, in vitro across many human tissues and organs is the key to both efficient transplant generation and predictive preclinical testing regimes. The hair follicle is an organoid that has been much studied based on its ability to grow quickly and to regenerate after trauma. Replacing hair lost due to pattern baldness or more severe alopecia, including that induced by chemotherapy, remains a significant unmet medical need. By carefully analyzing and recapitulating the growth and differentiation mechanisms of hair follicle formation, we recreated human hair follicles in tissue culture that were capable of producing a hair shaft and revealed a striking similarity to their in vivo counterparts. Extensive molecular and electron microscopy analysis were used to track the assembly of follicular keratinocytes, melanocytes and fibroblasts into the final hair shaft producing microfollicle architecture. The hair follicle generation process was optimized in terms of efficiency, reproducibility and compliance with regulatory requirements for later transplantation. In addition, we developed a procedure to integrate the de novo created human microfollicles into our existing chip-based human skin equivalents for substance testing. This would allow the evaluation of the role of hair follicles in dermal substance transport mechanisms for cosmetic products. Finally, we describe the challenges and opportunities we are facing for first-in-man transplantation trials.