The upper region of the outer root sheath of vibrissal follicles of adult mice contains multipotent stem cells that respond to morphogenetic signals to generate multiple hair follicles, sebaceous glands, and epidermis, i.e., all the lineages of the hairy skin. At the time when hair production ceases and when the lower region of the follicle undergoes major structural changes, the lower region contains a significant number of clonogenic keratinocytes, and can then respond to morphogenetic signals. This demonstrates that multipotent stem cells migrate to the root of the follicle to produce whisker growth. Moreover, our results indicate that the clonogenic keratinocytes are closely related, if not identical, to the multipotent stem cells, and that the regulation of whisker growth necessitates a precise control of stem cell trafficking.

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The epidermis and its related appendages such as the hair follicle constitute the epithelial compartment of the skin. The exact location and distribution ofthe keratinocyte colony-forming ceils within the epidermis or its appendages are unknown. We report that in the rat vibrissa, keratinocyte colony-forming cells are highly clustered in the bulgecontaining region. Approximately 95% of the total colonies formed in culture from fractionated vibrissae were in this location and fewer than 4% were located in the matrix area of the follicle. Finer dissection of the bulge-containing region located the colony-forming cells in the smafl part containing the bulge itself. The segregation of keratinocyte colony-forming cells in the bulge confims the hypothesis that the bulge is the reservoir of the stem cells responsible for the long-term growth of the hair follicle and perhaps of the epidermis as well.Hairs are specialized epidermal appendages which are characteristic of mammals. The hairy coat plays a significant role in temperature regulation, and also functions as a camouflage. Some hairs, such as the whiskers, have evolved as tactile organs and are important for animal behavior. In the human, the hairs are not as crucial and are generally viewed more as a cosmetic advantage. Nevertheless, the hair follicle provides a reservoir of keratinocytes which can be recruited to reepithelialize a skin defect (1). Hairs develop from the primitive epidermis during fetal life (2, 3). The inductive signals are believed to be released by the mesenchymal cells that constitute the dermal papilla (4-6). The exact nature of these signals is still unknown, although epimorphin, a membrane protein reported as essential for epithelial morphogenesis, may play a role (7). Follicular keratinocytes acquire a specific program of proliferation and differentiation as illustrated by the expression of the hair keratin genes (8-10). One of the most striking features of the hair is its carefully regulated growth cycle. Each cycle is a succession of three phases. The active growth phase (anagen) is followed by a regression phase (catagen) and then by a resting phase (telogen) after which growth resumes. The factors regulating these different phases are not understood. Cells with enough proliferative capability must exist in the hair follicle to provide differentiated progeny for the life time of the animal (11). The exact location of these cells within the hair follicle is not known with certainty. The follicular stem cells have long been thought to reside in the matrix where an intense proliferative activity takes place during the anagen phase (12)(13)(14). Particularly insightful work on this problem by Cotsarelis et al. (13) led to the discovery that follicular cells retaining [3H]thymidine were located in the bulge region close to the insertion of the arrector pili muscle. These data, along with previous histological findings (2, 15-18), make the bulge a tempting candidate for the site of the follicular stem cells. Cultivation of follicular...

A secreted luciferase from the marine ostracod, Vargula hilgendorfii, is a useful tool for gene expression assays in living mammalian cells. We have cloned the cDNA of a new secreted luciferase from the ostracod Cypridina noctiluca, which inhabits the coast of Japan. C. noctiluca luciferase consists of 553 amino acid residues with a molecular mass of 61,415 Da, as deduced from the nucleotide sequence. The homologies of nucleotide and amino acid sequences with V. hilgendorfii luciferase are 79.2% and 83.1%, respectively. C. noctiluca luciferase can expressed in and secreted from cultured mammalian cells. The characteristic properties of expressed C. noctiluca luciferase are similar to those of V. hilgendorfii luciferase. However, the activity of C. noctiluca luciferase in culture medium is much higher than that of V. hilgendorfii luciferase, suggesting that C. noctiluca luciferase is a highly potent reporter enzyme for real-time and continuous monitoring of gene expression in living cells.

Nanoparticles with a diameter of o100 nm are regarded as potential medical materials, as this size allows nanoparticles to circulate in vivo and possibly reach targeted tumors. Inorganic nanoparticles in particular are able to interact with light and/or magnetic fields, thus extending their potential applications to such fields as fluorescence labeling, magnetic resonance imaging and stimulus-responsive drug delivery that are essential to the diagnosis and treatment of disease. To facilitate their use in such applications, the appropriate design of surface ligands on these nanoparticles is necessary. The surface ligands determine the physicochemical properties of the surface, such as hydrophilicity/hydrophobicity and zeta potential as well as dispersibility in solution. These properties have an especially important role in determining nanoparticle-cell associations, such as cellular membrane permeability, immune responses and localization in vivo. This review focuses on recent advances in the surface engineering of nanoparticles for therapeutic applications.