Methods for generating cells of the inner ear, e.g., hair cells and supporting cells, from stem cells, e.g., mesenchymal stem cells, are provided, as well as compositions including the inner ear cells. Methods for the therapeutic use of the inner ear cells for the treatment of hearing loss are also described.

The invention relates to the use of matrix cells for obtaining a micro hair follicle and to the use thereof for evaluating the effect of cosmetic, pharmaceutical or dermatological products and also for the prophylactic or therapeutic treatment of a state of reduced pilosity.

The present disclosure relates to a bioengineering process to derive hair follicles in vitro from the in vitro disposition and differentiation of autologous pluripotent stem cells and dermal papilla stem cells. The present disclosure also relates to the in vitro bioengineering of hypoimmunogenic hair follicles from allogenic pluripotent stem cells and dermal papilla stem cells. The present disclosure also relates to bioengineering of autologous and allogenic hypoimmunogenic hair follicles and hair follicle containing sheets with asymmetric disposition of hair shafts. The present disclosure also relates to a bioengineering process to derive hair follicle containing sheets in vitro from a biodegradable supportive grid and said in vitro derived hair follicles. The present disclosure also relates to the controlled asymmetry of the hair shaft on said hair follicle containing sheets. The present disclosure also relates to the field of cosmetic materials and method for reconstructing hair follicle containing materials in vitro.

Provided is a medium composition for differentiation of a human induced pluripotent stem cell to a dermal papilla precursor cell, a differentiation method, and a use for inducing hair follicle neogenesis using the differentiated dermal papilla precursor cell. Further provided is a method for differentiating a human induced pluripotent stem cell into a dermal papilla precursor cell having hair follicle forming ability and a composition of a dermal papilla precursor cell specific differentiation medium for the above differentiation, and have effectively induced hair follicle neogenesis consisting only of human cells without conventional mouse-human hybrid hair follicles by using the human induced dermal papilla precursor cell and a human induced epidermal precursor cell obtained through the differentiation method. Human hair follicle tissue produced is expected to be useful as a therapeutic method for patients suffering from hair loss by overcoming the limitations of hair loss treatments.

Compositions and provided to induce cells of the inner ear to renter the cell cycle and to proliferate. In particular, hair cells are induced to proliferate by administration of a composition which activates the Myc and Notch. Supporting cells are induced to transdifferentiate to hair cells by inhibition of Myc and Notch activity or the activation of Atoh1. Methods of treatment include the intracellular delivery of these molecules to a specific therapeutic target.

The present invention recognizes that there exists a long felt need for reliable hair growth methods and compositions that do not suffer from side effects and limitations of current technologies, such as surgery using a subject's own hair and pharmaceutical compositions. A first aspect of the present invention is a method of making at least one three dimensional collection of cells capable of forming a functional hair follicle. A second aspect of the present invention is a product produced by the method of making at least one three dimensional collection of cells capable of forming a functional hair follicle of the present invention. A third aspect of the present invention is a method of making at least one functional hair follicle. A fourth aspect of the present invention is a product produced by the method of making at least one functional hair follicle of the present invention. A fifth aspect of the present invention is a method of hair growth in a subject using at least one three dimensional collection of cells capable of forming a functional hair follicle of the present invention. A sixth aspect of the present invention is a method of hair growth in a subject using at least one functional hair follicle of the present invention.

The invention provides compositions and methods for treating or preventing hearing loss in a subject. The method comprises administering to the subject in need thereof, at least Myc or an agent that increases the expression of Myc in an inner ear organ, or associated neural structures, of the subject so as to treat or prevent the hearing loss.

The present invention relates to a method for producing hair microfollicles comprising the steps of: a) providing de novo papillae, b) providing other cell populations selected from the group of fibroblasts, keratinocytes and melanocytes, and co-culturing the de novo papillae with at least one other cell population in non-adherent culture vessels. The present invention relates also to methods of producing de novo papillae usable in said method for producing hair microfollicles.

Provided is a hair follicle germ capable of forming a hair shaft-like structure in vitro simply and within a short period of time. A method of producing a hair follicle germ includes: inoculating epithelial cells and mesenchymal cells; maintaining the epithelial cells and the mesenchymal cells in a culture solution in which (a) laminin and entactin, and/or (b) type IV collagen is dispersed; and co-culturing the epithelial cells and the mesenchymal cells in a culture solution to form a hair follicle germ.

The invention in relates in part to a method for rejuvenating hair follicles, the method comprising the steps of: (1) obtaining androgen non-inhibited cells from hair follicle tissue; (2) culturing the androgen non-inhibited cells to produce an expanded population of androgen-non-inhibited cells; and (3) implanting the expanded population of androgen non-inhibited cells proximal to miniaturised and/or miniaturising hair follicles.