The use of ectopic volar fibroblasts to modify skin identity
Sam Lee, Sam S. Lee, Evan Sweren, Erika Dare, Paige Derr, Kristy Derr, Chen Chia Wang, Brooke Hardesty, A. Willis, Junjie Chen, J. Vuillier, Joseph Du, Julia Wool, Amanda Ruci, V. Wang, Chaewon Lee, Sampada Iyengar, Soichiro Asami, Maria Daskam, Claudia Lee, J. Lee, D. Cho, Joshua Kim, E. G. Martinez Peña, So Min Lee, So Min Lee, Xu He, Michael Wakeman, Iralde Sicilia, Dalhart T. Dobbs, Amy van Ee, Ang Li, Yingchao Xue, Kaitlin L. Williams, Charles Kirby, Dongwon Kim, Sooah Kim, Lillian Xu, Ruizhi Wang, Marc Ferrer, Yun Chen, Jin U. Kang, Reza Kalhor, Sewon Kang, Luis A. Garza
Abstract
Skin identity is controlled by intrinsic features of the epidermis and dermis and their interactions. Modifying skin identity has clinical potential, such as the conversion of residual limb and stump (nonvolar) skin of amputees to pressure-responsive palmoplantar (volar) skin to enhance prosthesis use and minimize skin breakdown. Greater keratin 9 ( KRT9 ) expression, higher epidermal thickness, keratinocyte cytoplasmic size, collagen length, and elastin are markers of volar skin and likely contribute to volar skin resiliency. Given fibroblasts’ capacity to modify keratinocyte differentiation, we hypothesized that volar fibroblasts influence these features. Bioprinted skin constructs confirmed the capacity of volar fibroblasts to induce volar keratinocyte features. A clinical trial of healthy volunteers demonstrated that injecting volar fibroblasts into nonvolar skin increased volar features that lasted up to 5 months, highlighting a potential cellular therapy.