Characterization of hair follicle development in engineered skin substitutes

Generation of skin appendages in engineered skin substitutes has been limited by lack of trichogenic potency in cultured postnatal cells. To investigate the feasibility and the limitation of hair regeneration, engineered skin substitutes were prepared with chimeric populations of cultured human kera...

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Published inPloS one Vol. 8; no. 6; p. e65664
Main Authors Sriwiriyanont, Penkanok, Lynch, Kaari A, McFarland, Kevin L, Supp, Dorothy M, Boyce, Steven T
Format Journal Article
LanguageEnglish
Published United States Public Library of Science 17.06.2013
Public Library of Science (PLoS)
Subjects
Animals
Appendages
Biology
Cells, Cultured
Collagen
Dermatology
Desaturase
Excavation
Feasibility studies
Fibroblasts
Follicles
Genetic engineering
Glands
Growth factors
Hair
Hair Follicle - growth & development
Keratinocytes
Medicine
Mice
Mice, Nude
Neonates
Real-Time Polymerase Chain Reaction
Regeneration
Sebaceous glands
Sebaceous Glands - physiology
Skin
Skin, Artificial
Stem cells
Studies
Substitutes
Surgery
Transgenic mice
Water loss
Wounds
United States > US
Ohio
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Summary:Generation of skin appendages in engineered skin substitutes has been limited by lack of trichogenic potency in cultured postnatal cells. To investigate the feasibility and the limitation of hair regeneration, engineered skin substitutes were prepared with chimeric populations of cultured human keratinocytes from neonatal foreskins and cultured murine dermal papilla cells from adult GFP transgenic mice and grafted orthotopically to full-thickness wounds on athymic mice. Non-cultured dissociated neonatal murine-only skin cells, or cultured human-only skin keratinocytes and fibroblasts without dermal papilla cells served as positive and negative controls respectively. In this study, neonatal murine-only skin substitutes formed external hairs and sebaceous glands, chimeric skin substitutes formed pigmented hairs without sebaceous glands, and human-only skin substitutes formed no follicles or glands. Although chimeric hair cannot erupt readily, removal of upper skin layer exposed keratinized hair shafts at the skin surface. Development of incomplete pilosebaceous units in chimeric hair corresponded with upregulation of hair-related genes, LEF1 and WNT10B, and downregulation of a marker of sebaceous glands, Steroyl-CoA desaturase. Transepidermal water loss was normal in all conditions. This study demonstrated that while sebaceous glands may be involved in hair eruption, they are not required for hair development in engineered skin substitutes.
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Competing Interests: Dr. Boyce is the named inventor on patents and patent applications assigned to the University of Cincinnati and Shriners Hospitals for Children according to their intellectual property policies. Patents, patent applications and other intellectual property pertaining to engineered skin substitutes are licensed to Cutanogen Corporation which was founded by Dr. Boyce, and in which he has past and present financial interests. Dr. Boyce resigned as an officer of Cutanogen in 2006, and he has no authority or responsibility for Cutanogen’s current activities. Dr. Boyce also is a paid consultant for Aderans Research Institute (ARI). No funding for the reported studies was provided by ARI, and ARI has no rights to any technologies invented by Dr. Boyce. Other authors declare no conflict of interest. This does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials.
Conceived and designed the experiments: PS DS SB. Performed the experiments: PS KL DS KM. Analyzed the data: PS SB KM. Contributed reagents/materials/analysis tools: DS SB. Wrote the paper: PS.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0065664