Invited review article
Review of hair follicle dermal cells

https://doi.org/10.1016/j.jdermsci.2009.11.005Get rights and content

Abstract

Hair follicle stem cells in the epithelial bulge are responsible for the continual regeneration of the hair follicle during cycling. The bulge cells reside in a niche composed of dermal cells. The dermal compartment of the hair follicle consists of the dermal papilla and dermal sheath. Interactions between hair follicle epithelial and dermal cells are necessary for hair follicle morphogenesis during development and in hair reconstitution assays. Dermal papilla and dermal sheath cells express specific markers and possess distinctive morphology and behavior in culture. These cells can induce hair follicle differentiation in epithelial cells and are required in hair reconstitution assays either in the form of intact tissue, dissociated freshly prepared cells or cultured cells. This review will focus on hair follicle dermal cells since most therapeutic efforts to date have concentrated on this aspect of the hair follicle, with the idea that enriching hair-inductive dermal cell populations and expanding their number by culture while maintaining their properties, will establish an efficient hair reconstitution assay that could eventually have therapeutic implications.

Section snippets

Dermal cells in hair morphogenesis and cycling

During embryonic hair follicle development, mesenchymal cells aggregate immediately below the epidermis in a patterned manner. These aggregates or “condensates” mark the location of the new hair follicle. The mesenchymal condensates maintain close contact with the base of down-growing epithelial columns and are eventually ensheathed by the hair bulb during the peg stage [17]. In a fully developed anagen hair follicle, the DP resides deep in the subcutaneous fat and is surrounded by hair matrix

Techniques for isolating and culturing dermal cells

The most widely used method to isolate DP is surgical micro-dissection, which has been well established in rat and murine vibrissae follicles as well as human hair follicles [28], [29]. Surgical micro-dissection has also been used to isolate DS adjacent to DP [11], [12]. However, the technique is laborious and time-consuming. Outgrowths of cells from DP explants can be expected within 1 week in culture medium. Cultured DP cells show flattened and polygonal morphology and tend to grow into

Biochemical and molecular signatures of dermal cells

Cells within DP and DS are specialized mesenchymal cells and express specific enzymes and molecules. Although the functions of most marker proteins are unknown, they have been widely used to identify DP and DS. The expression of some markers, e.g. alkaline phosphatase and versican correlates with hair inductive properties.

Dermal cells in hair reconstitution assays and maintenance of hair inductivity

The hair inductive property of dermal cells, especially DP cells, has been clearly demonstrated. The epithelial part of a pre-existing hair follicle needs a DP to maintain its growth, and dissociated epidermal cells require the guidance of dermal cells to be organized into complicated hair structures, otherwise, a simple epithelial cyst forms. Therefore, dermal cells are critical in hair regeneration assay and it is important to keep dermal cells inductive during preparation.

Maintaining hair inductivity in dermal cell culture

It is important to keep cells competent in hair regeneration assays while processing and expanding them in culture. However, it is known that cultured DP cells gradually lose their hair inductivity and proliferative capacity after being passaged [30], [59].

Dermal cells in hair diseases

The role of the DP in diseases of skin and hair is not known, but some have speculated that androgenetic alopecia, which is characterized by miniaturized hair follicles and shortening of anagen phase in a defined pattern, may be due to the effect of testosterone and dihydrotestosterone acting on androgen receptors in the DP and causing changes in transcription of genes such as TGF-β and IGF-1 [65], [66], [67]. Androgens may also drive the DP to secret inhibitory autocrine factors [68]. Bahta et

Conclusion

Dermal cells play a pivotal role in the regulation of hair growth. For hair follicle regeneration purposes, important issues include isolation of inductive dermal population, expanding their number by culture, maintenance of their hair inductive property and providing them an adequate niche and exogenous signals to enhance their interaction with epidermal cells toward the fate of hair neogenesis. An ideal hair regeneration model for human hair follicles has yet to be developed. The efficiency

Acknowledgements

The career of GC was supported by NIAMS/NIH, Dermatology Foundation, and the Edwin and Fannie Gray Hall Center for Human Appearance. CCY was supported by a grant from L’Oreal and scholarships from National Science Council, Taiwan and National Cheng Kung University Hospital, Tainan, Taiwan.

Dr. Chao-Chun Yang is doing his postdoctoral research in Dr. George Cotsarelis’ laboratory in University of Pennsylvania, USA since 2008. He received his MD degree in National Cheng Kung University, Tainan, Taiwan in 1999. After finishing residency training, he served as an attending physician and ran the hair clinics in the Department of Dermatology, National Cheng Kung University Hospital, Tainan, Taiwan since 2005. His current research is focused on developing hair reconstitution assays.

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    Dr. Chao-Chun Yang is doing his postdoctoral research in Dr. George Cotsarelis’ laboratory in University of Pennsylvania, USA since 2008. He received his MD degree in National Cheng Kung University, Tainan, Taiwan in 1999. After finishing residency training, he served as an attending physician and ran the hair clinics in the Department of Dermatology, National Cheng Kung University Hospital, Tainan, Taiwan since 2005. His current research is focused on developing hair reconstitution assays.

    George Cotsarelis (MD) is the Albert M. Kligman Professor of dermatology at the University of Pennsylvania School of Medicine in Philadelphia where he is the Director of the Hair and Scalp Clinic and Director of the Program on Epithelial Regeneration and Stem Cells, University of Pennsylvania Institute for Regenerative Medicine. He received his MD from the University of Pennsylvania School of Medicine, where he also completed his Dermatology Residency and a Howard Hughes sponsored Fellowship for Physicians in molecular biology. He is the first to identified and localized stem cells in the hair follicles of both mice and humans. The hair follicle stem cells are located in a unique area called the bulge. Since the identification of these cells, he has developed means for isolating, characterizing and manipulating them. He first demonstrated that isolated hair follicle stem cells could generate new hair follicles when injected into immunodeficient mice. His research areas of interest include epithelial stem cells, hair follicle biology, wound healing and skin regeneration.

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