Optimization of cell construct grafting procedure for hair regeneration therapy

  • Dr Noriyuki Aoi, Department of Plastic Surgery, University of Tokyo, Japan
  • Dr Keita Inoue, Department of Plastic Surgery, University of Tokyo, Japan
  • Dr Kotaro Yoshimura, Department of Plastic Surgery, University of Tokyo, Japan

Objective: Although many attempts have been done, expanded DPC transplantation therapies for hair regeneration have not yet succeeded in human. There remain two major challenging factors; 1) functional limitations of expanded DPCs obtained from human adult hair follicles, and 2) absence of clinically applicable methodology of DPC transplantation. The purpose of this study was to seek a clinically acceptable (efficient, minimally-invasive and economical) transplantation procedure to enable functional interaction between epithelial and dermal key components.
Methods: We designed and tested five clinically applicable transplantation procedures which were referred to as Pinhole, Laser, Slit, Non-vascularized sandwich (NVS), and hemi-vascularized sandwich (HVS) methods, respectively. Other well-known models such as patched assay and the chamber method were regarded as clinically inapplicable. Labeled rat dermal papilla tissues (DPT) or cultured DPC sheet fragments were transplanted to the sole skin in transposed mice foot, and hair follicle regeneration (number, maturation stage, and regulation stage of follicles) was histologically evaluated at 8 weeks.
Results: Regenerated follicles and labeled DPT were detected in all models, but some follicles appeared dysregulated such as cystic or inverted phenotypes. Follicle induction rate per transplanted DPT was significantly higher in HVS method than any other methods and the number of matured follicles (at maturation stages 6-8) was also highest in HVS method. Failure (no hair follicle) sample rate was highest in NVS method. Actual hair growth emerging from the skin was detected only in HVS method both with DPT and cultured DPCs transplantation.
Conclusions: The results strongly suggested that direct contact of epithelial and dermal components and better oxygenation (vascularity) are crucial for hair regeneration. We conclude that the HVS method is an effective transplantation method of a cultured DPC construct and easily applicable in the clinical settings due to its minimal invasiveness and no need of preparation of epithelial cells.