Stem cell stimulating compositions and methods

Abstract

The inventive subject is directed towards ready-to-use topical cosmetic formulations that include at least one defensin present in sub-antimicrobially effective concentrations. Surprisingly, even at such low concentrations, defensins recruit LGR6+ stem cells from hair follicles to the interfollicular space. Including defensins in the inventive topical cosmetic formulations may reduce one or more of wrinkle depth, wrinkle length, wrinkle width, pore size, irregularity in texture of a skin surface, oiliness, brown spots, and red spots in non-injured skin, thus reducing apparent age.

1 .- 218 . (canceled) 
     
     
         219 . A topical anti-aging formulation, comprising:
 a cosmetically acceptable carrier and a first defensin,   wherein the first defensin is present in the topical anti-aging formulation at a sub-antimicrobially effective concentration.   
     
     
         220 . The topical anti-aging formulation of  claim 219 , wherein the first defensin is present in the topical anti-aging formulation at a concentration effective to recruit LGR6+ cells to an interfollicular space in a non-injured skin. 
     
     
         221 . The topical anti-aging formulation of  claim 219 , wherein the first defensin comprises alpha-defensin 1, alpha-defensin 5, alpha-defensin 6, neutrophil defensin 1, neutrophil defensin 2, neutrophil defensin 3, neutrophil defensin 4, theta-defensin, beta-defensin 1, beta-defensin 2, beta-defensin 3, or beta-defensin 4. 
     
     
         222 . The topical anti-aging formulation of  claim 219 , wherein the first defensin is encapsulated in a liposome or nanoparticle. 
     
     
         223 . The topical anti-aging formulation of  claim 219 , wherein the first defensin comprises a synthetic defensin, a recombinant defensin, a human defensin, a monkey defensin, a mouse defensin, a rat defensin, a bovine defensin, a sheep defensin, a horse defensin, a rabbit defensin, a swine defensin, a dog defensin, or a cat defensin. 
     
     
         224 . The topical anti-aging formulation of  claim 219 , wherein the sub-antimicrobially effective concentration of the first defensin is between 1 picogram per milliliter and 100 milligram per milliliter. 
     
     
         225 . The topical anti-aging formulation of  claim 219 , wherein the sub-antimicrobially effective concentration of the first defensin is between 1 and 30 ng/ml. 
     
     
         226 . The topical anti-aging formulation of  claim 219 , wherein the first defensin is present in the topical anti-aging formulation at a concentration that is effective to substantially reduce wrinkle depth, wrinkle length, wrinkle width, pore size, irregularity in texture of a skin surface, oiliness, brown spots, or red spots in a non-injured skin. 
     
     
         227 . The topical anti-aging formulation of  claim 219 , wherein the first defensin is associated with a protein carrier. 
     
     
         228 . The topical anti-aging formulation of  claim 219 , further comprising a supplement for LGR6+ stem cells, wherein the supplement comprises human serum albumin, recombinant albumin, bovine serum albumin, egg albumin, plant hydrolysate, beta-cyclodextrin, glutamine, phospholipids, fibronectin, hyaluronate, hyaluronic acid, epidermal growth factor, fibroblast growth factor, plant hydrolysate, L-alanyl-Lglutamine, gelatin, recombinant gelatin, vitamin E. Tocopheryl Nicotinate, Coenzyme Q10, or ubiquinone. tocopheryl acetate, leuconostoc/radish root ferment filtrate, fibronectin, L-alanyl-L-glutamine, vitamin B complex,  Carthamus tinctorius  (sunflower) oleosomes, C12-15 alkyl benzoate, sodium acyloyldimethyltaurate/VP crosspolymer, resveratrol, retinyl palmitate, ascorbyl palmitate, phenoxyethanol, caprylyl glycol, ethylhexylglycerin, hexylene glycol, panthenol, folic acid, green tea extract, chamomile extract, saccharide isomerate,  Borago officinalis  seed oil, tocopheryl, saccharomyces lysate extract, carrageenan, phenoxyethanol. 
     
     
         229 . The topical anti-aging formulation of  claim 219 , wherein the first defensin comprises alpha-defensin 5 or beta-defensin 3. 
     
     
         230 . The topical anti-aging formulation of  claim 219 , further comprising a second defensin, 
     
     
         231 . The topical anti-aging formulation of  claim 230 , wherein the second defensin is different from the first defensin, and wherein the second defensin is present in the topical anti-aging formulation at a sub-antimicrobially effective concentration. 
     
     
         232 . The topical anti-aging formulation of  claim 230 , wherein the second defensin is different from the first defensin, and wherein the second defensin is present in the topical anti-aging formulation at a concentration effective to recruit LGR6+ cells to an interfollicular space in a non-injured skin. 
     
     
         233 . The topical anti-aging formulation of  claim 230 , wherein the second defensin comprises a synthetic defensin, a recombinant defensin, a human defensin, a monkey defensin, a mouse defensin, a rat defensin, a bovine defensin, a sheep defensin, a horse defensin, a rabbit defensin, a swine defensin, a dog defensin, or a cat defensin. 
     
     
         234 . The topical anti-aging formulation of  claim 230 , wherein the sub-antimicrobially effective concentration of the second defensin is between 1 picogram per milliliter and 100 milligram per milliliter. 
     
     
         235 . The topical anti-aging formulation of  claim 230 , wherein the sub-antimicrobially effective concentration of the second defensin is between 1 and 30 ng/ml. 
     
     
         236 . The topical anti-aging formulation of  claim 230 , wherein the second defensin is present in the topical anti-aging formulation at a concentration that is effective to substantially reduce wrinkle depth, wrinkle length, wrinkle width, pore size, irregularity in texture of a skin surface, oiliness, brown spots, or red spots in a non-injured skin. 
     
     
         237 . The topical anti-aging formulation of  claim 219 , further comprising an activator of defensin-gene expression. 
     
     
         238 . The topical anti-aging formulation of  claim 219 , further comprising a UV blocking agent. 
     
     
         239 . An ocular composition for treatment or prevention of a corneal wound or condition, comprising: one or more defensins in a carrier acceptable for topical application to an eye of a mammal, and present in a concentration effective to accelerate healing of a wound or recruiting epithelial stem cells or limbal stem cells to an epithelial layer of a cornea. 
     
     
         240 . A method of treating corneal wounds or conditions comprising: administering the ocular composition of  claim 239  in an amount and under a protocol to accelerate healing of a wound or recruit epithelial stem cells or limbal stem cells to an epithelial layer of a cornea.