Restoration of the epidermal phenotype by follicular outer root sheath cells in recombinant culture with dermal fibroblasts

Limat, Alain; Breitkreutz, Dirk; Hunziker, Thomas; Boillat, Colette; Wiesmann, Ulrich; Klein, E.; Noser, Friedrich; Fusenig, Norbert E.

doi:10.1016/0014-4827(91)90357-z

Cited by 51 publications

(33 citation statements)

References 41 publications

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“…2). This is in aggreement with previous reports [1,23,24,31]. The amounts of suprabasal, differentiation-specific keratins K1 (68 kDa) and K10 (58 kDa) varied between different ORS cell strains, although remaining usually very weak.…”

Section: Resultssupporting

confidence: 89%

Proliferation and differentiation of cultured human follicular keratinocytes are not influenced by biotin

et al. 1996

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In humans and in animals, biotin deficiency causes pathological changes in the skin and its appendages. High doses of biotin may also have beneficial effects on skin, hair and fingernails in humans and animals with normal biotin status. Therefore, we investigated the effects of low and high concentrations of biotin on proliferation and differentiation of cultured outer root sheath cells from human hair follicles as an in vitro model for skin. The activities of biotin-dependent carboxylases were measured to evaluate the biotin status of the cells. In monolayer cultures of outer root sheath cells, proliferation and expression of the differentiation-specific keratins K1 and K10 were not influenced by extremely low concentrations of biotin (<2 x 10(-10) mol/l) or by pharmacological doses of biotin (10(-5) mol/l). Biotin deficiency of the cells was confirmed under the former condition by demonstrating decreased activities of the mitochondrial carboxylases. In organotypic cocultures of outer root sheath cells and dermal fibroblasts, in which stratified epithelia resembling epidermis were developed, the biotin concentration had no effect on the expression of all tested epidermal differentiation markers, including the suprabasal keratins K1 and K10, the hyperproliferation-associated keratin K16, involucrin and filaggrin.

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Section: Resultssupporting

confidence: 89%

Proliferation and differentiation of cultured human follicular keratinocytes are not influenced by biotin

et al. 1996

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“…Generally, the epithelium formed by ORS cells was more hyperplastic than that observed with epider mal keratinocytes (HEK). Although the total thickness of these epithelia was largely com parable, the Malpighi stratum formed by ORS cells was much thicker, while the stratum granulosum was less apparent and the horny layer very thin [14,16]. Obviously, HDFderived factors were essential, since without …”

Section: In Primary Culturesmentioning

confidence: 99%

“…Cryostat sections of 8 pm were air-dried, rehydrated with PBS and incu bated according to standard protocols [14,16] with the antibodies listed in table 2. (table 1).…”

Section: Cellsmentioning

confidence: 99%

“…12]. 6 x 105 ORS cells or HMC were plated per cm2 onto these gels, grown submerged in FAD medium [ 13] for 4-7 days, and finally lifted at the air-medium interface and grown for an additional 7 or 14 days [14], Cultures in Matrigel. Cell-free collagen gels were prepared as described elsewhere [15], mounted in a CRD culture device, and overlaid by 0.1 ml of a sus pension of 10s ORS cells, HMC or human epidermal keratinocytes in Matrigel (Collaborative Research, Bedford, Mass.).…”

Section: Cellsmentioning

confidence: 99%

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Organotypic Cocultures as Models to Study Cell-Cell and Cell-Matrix Interactions of Human Hair Follicle Cells

Limat

Hunziker²,

Breitkreutz³

et al. 1994

Skin Pharmacol Physiol

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In the hair follicle complex interactions of specialized epithelial and mesenchymal cells as well as extracellular components are crucial for regulation of proliferation and differentiation. In order to mimic this situation in vitro, techniques to cultivate follicular cells such as outer root sheath (ORS) cells, hair matrix cells (HMC) and hair papilla cells (HPC) were developed. Human dermal fibroblasts (HDF) and HPC markedly enhanced proliferation of ORS cells when cocultured spatially separated in a two-chamber system, which was more pronounced with postmitotic than with mitotic mesenchymal cells. In organotypic cocultures of ORS cells on HDF- or HPC-populated collagen gels lifted at the air-medium interface, stratified epithelia developed largely reminiscent of the epidermis. The morphology was well structured and differentiation markers were expressed (e.g. suprabasal keratins, filag-grin, involucrin, basement membrane components). Both proliferation and differentiation were dependent on the presence of HDF or HPC. When grown embedded in extracellular matrix (Matrigel) without HDF, ORS cells formed large spheroids with inward directed differentiation. Also herein HDF or HPC sustained both cell growth and balanced, epidermis-type differentiation. While in organotypic cocultures with HDF, HMC also organized into stratified epithelia, epidermis-type stratification was prevented by HPC. Similarly, in the presence of HDF, HMC in Matrigel formed keratinizing spheroids, whereas this was largely suppressed in the presence of HPC. However, hair-type differentiation was not observed, suggesting a crucial role of other yet unknown components or of the surrounding matrix.

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“…Skin substitutes are composed of two compartments, dermis and epidermis, and as a minimum requirement organotypic skin should possess normal dermal and epidermal morphology and a well-defined basement membrane. Hair follicle outer root sheath (ORS) cells have frequently been used as the epithelial source in organotypic recombinations, where interestingly they assume a keratinocyte phenotype and are thought to produce an improved basement membrane (22)(23)(24)(25)(26). Indeed, follicle epithelial cells, recognized increasingly as an important stem cell repository for skin as well as hair follicles (27), are now used as the epidermal source in commercial skin replacement products.…”

Section: Introductionmentioning

confidence: 99%

Plasticity of hair follicle dermal cells in wound healing and induction

Gharzi

Reynolds

Jahoda

2003

Experimental Dermatology

228

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Gharzi A, Reynolds AJ, Jahoda CAB. Plasticity of hair follicle dermal cells in wound healing and induction. Exp Dermatol 2003: 12: 126-136. # Blackwell Munksgaard, 2003 Abstract: The capacity of adult hair follicle dermal cells to participate in new follicle induction and regeneration, and to elicit responses from diverse epithelial partners, demonstrates a level of developmental promiscuity and influence far exceeding that of interfollicular fibroblasts. We have recently suggested that adult follicle dermal cells have extensive stem or progenitor cell activities, including an important role in skin dermal wound healing. Given that up to now tissue engineered skin equivalents have several deficiencies, including the absence of hair follicles, we investigated the capacity of follicle dermal cells to be incorporated into skin wounds; to form hair follicles in wound environments; and to create a hair follicle-derived skin equivalent. In our study, we implanted rat follicle dermal cells labelled with a vital dye into ear and body skin wounds. We found that they were incorporated into the new dermis in a manner similar to skin fibroblasts, but that lower follicle dermal sheath also assimilated into hair follicles. Using different combinations of follicle dermal cells and outer root sheath epithelial cells in punch biopsy wounds, we showed that new hair follicles were formed only with the inclusion of intact dermal papillae. Finally by combining follicle dermal sheath and outer root sheath cells in organotypic chambers, we created a skin equivalent with characteristic dermal and epidermal architecture and a normal basement membrane -the first skin to be produced entirely from hair follicle cells. These data support the hypothesis that follicle dermal cells may be important in wound healing and demonstrate their potential usefulness in human skin equivalents and skin substitutes. While we have made progress towards producing skin equivalents that contain follicles, we suggest that the failure of cultured dermal papilla cells to induce follicle formation in wounds illustrates the complex role the follicle dermis may play in skin. We believe that it demonstrates a genuine dichotomy of activity for follicle cells within skin.

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Restoration of the epidermal phenotype by follicular outer root sheath cells in recombinant culture with dermal fibroblasts

Cited by 51 publications

References 41 publications

Proliferation and differentiation of cultured human follicular keratinocytes are not influenced by biotin

Proliferation and differentiation of cultured human follicular keratinocytes are not influenced by biotin

Organotypic Cocultures as Models to Study Cell-Cell and Cell-Matrix Interactions of Human Hair Follicle Cells

Plasticity of hair follicle dermal cells in wound healing and induction

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