The use of ectopic volar fibroblasts to modify skin identity

Author:

Lee Sam S.1ORCID,Sweren Evan1ORCID,Dare Erika1ORCID,Derr Paige2,Derr Kristy2,Wang Chen Chia1ORCID,Hardesty Brooke1ORCID,Willis Aiden A.1ORCID,Chen Junjie3ORCID,Vuillier Jonathan K.1ORCID,Du Joseph1ORCID,Wool Julia1ORCID,Ruci Amanda1ORCID,Wang Vicky Y.1ORCID,Lee Chaewon1ORCID,Iyengar Sampada1ORCID,Asami Soichiro4ORCID,Daskam Maria1ORCID,Lee Claudia1,Lee Jeremy C.1ORCID,Cho Darren1ORCID,Kim Joshua1,Martinez-Peña Eddie Gibson1ORCID,Lee So Min1ORCID,He Xu1,Wakeman Michael1,Sicilia Iralde1,Dobbs Dalhart T.1ORCID,van Ee Amy1ORCID,Li Ang1ORCID,Xue Yingchao1ORCID,Williams Kaitlin L.1ORCID,Kirby Charles S.1ORCID,Kim Dongwon1ORCID,Kim Sooah1ORCID,Xu Lillian1ORCID,Wang Ruizhi1,Ferrer Marc2,Chen Yun3ORCID,Kang Jin U.5ORCID,Kalhor Reza4ORCID,Kang Sewon1ORCID,Garza Luis A.167ORCID

Affiliation:

1. Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.

2. Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD 20850, USA.

3. Department of Mechanical Engineering, Johns Hopkins University, MD 21210, USA.

4. Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.

5. Department of Electrical and Computer Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.

6. Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.

7. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.

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.

Publisher

American Association for the Advancement of Science (AAAS)

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