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G Cotsarelis

Publications and source records attributed to G Cotsarelis.

26 records · Page 2Linked to original sources
PubMed1991

Relative proliferative rates of limbal and corneal epithelia. Implications of corneal epithelial migration, circadian rhythm, and suprabasally located DNA-synthesizing keratinocytes.

An important element of the recently proposed limbal stem cell model is that corneal epithelial cells migrate centripetally. The driving force for this migration is unknown, although it has been suggested that limbal epithelium, proliferates at a higher rate than central corneal epithelium, thus creating a population pressure toward the central cornea. This hypothesis was tested by measuring the relative proliferative rates of limbal and central corneal epithelia using 3H-thymidine autoradiographic techniques. The results indicate that, in both the New Zealand white rabbit and SENCAR mouse, the labeling index (LI) of limbal epithelium is actually lower than that of central corneal epithelium. This difference in LI persists throughout the circadian rhythm cycle. These results suggest that population pressure per se cannot be responsible for the centripetal migration of corneal epithelium and raise the possibility that preferential desquamation of central corneal epithelium may "draw" peripheral cells toward the central cornea. In both epithelia, the LI peak precedes the mitotic index (MI) peak during circadian cycle by 4-6 hr. These data therefore are in close agreement with earlier results on several nonocular stratified epithelia but contradict an earlier suggestion that the LI and MI peaks of corneal epithelium coincide. Finally, although most of the 3H-thymidine incorporating cells in central cornea may appear to be suprabasally located, they are only partially displaced into the suprabasal compartment. In most cases, such cells are still connected with the basement membrane through a thin stalk of cytoplasm. Since corneal epithelium rests on an exceptionally flat and rigid substratum, an increase in cellular volume in DNA-synthesizing cells may not be tolerated well in an already crowded basal layer. This may explain why an unusually large proportion of DNA-synthesizing cells are expelled preferentially into either a "second tier basal layer" or into the suprabasal compartment.

Animals↗
PubMed1990

Label-retaining cells reside in the bulge area of pilosebaceous unit: implications for follicular stem cells, hair cycle, and skin carcinogenesis.

Inconsistent with the view that hair follicle stem cells reside in the matrix area of the hair bulb, we found that label-retaining cells exist exclusively in the bulge area of the mouse hair follicle. The bulge consists of a subpopulation of outer root sheath cells located in the midportion of the follicle at the arrector pili muscle attachment site. Keratinocytes in the bulge area are relatively undifferentiated ultrastructurally. They are normally slow cycling, but can be stimulated to proliferate transiently by TPA. Located in a well-protected and nourished environment, these cells mark the lower end of the "permanent" portion of the follicle. Our findings, plus a reevaluation of the literature, suggest that follicular stem cells reside in the bulge region, instead of the lower bulb. This new view provides insights into hair cycle control and the possible involvement of hair follicle stem cells in skin carcinogenesis.

Animals↗
PubMed1989

Existence of slow-cycling limbal epithelial basal cells that can be preferentially stimulated to proliferate: implications on epithelial stem cells.

Despite the obvious importance of epithelial stem cells in tissue homeostasis and tumorigenesis, little is known about their specific location or biological characteristics. Using 3H-thymidine labeling, we have identified a subpopulation of corneal epithelial basal cells, located in the peripheral cornea in a region called limbus, that are normally slow cycling, but can be stimulated to proliferate in response to wounding and to a tumor promotor, TPA. No such cells can be detected in the central corneal epithelium, suggesting that corneal epithelial stem cells are located in the limbus. A comparison of various types of epithelial stem cells revealed a common set of features, including their preferred location, pigment protection, and growth properties, which presumably play a crucial role in epithelial stem cell function.

Animals↗
PubMedDate not supplied

The hair follicle as a target for gene therapy.

The hair follicle possesses progenitor cells for continued hair follicle cycling and for epidermal keratinocytes, melanocytes and Langerhans cells. These different cell types can be targeted by topical gene delivery to mouse skin. Using a combination of liposomes and DNA, we demonstrated the feasibility of targeting hair follicle cells in human scalp xenografts as well. We defined liposome composition and stage of the hair cycle as important parameters influencing transfection of human hair follicles. Transfection occurred only during anagen onset. Considerations and obstacles for using gene therapy to treat alopecias and skin disease are discussed. A theoretical framework for future gene therapy treatments for cutaneous and systemic disorders is presented.

Administration, Cutaneous↗