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.

What is claimed is: 
     
         1 . A method of improving skin texture in a subject in need thereof, the method comprising:
 applying a topical formulation comprising a first defensin to a non-injured skin of the subject,   recruiting LGR6+ stems cells to an interfollicular space in the non-injured skin of the subject,   wherein the topical formulation reduces wrinkle depth, wrinkle length, wrinkle width, pore size, irregularity in texture of a skin surface, oiliness, brown spots, or red spots in the non-injured skin of the subject.   
     
     
         2 . The method of  claim 1 , wherein the first defensin is present in the topical formulation at a sub-antimicrobially effective concentration. 
     
     
         3 . The method of  claim 1 , 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. 
     
     
         4 . The method of  claim 1 , wherein the first defensin comprises a synthetic defensin, a human defensin, recombinant 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. 
     
     
         5 . The method of  claim 1 , wherein the first defensin is present in the topical formulation at a concentration between 1 picogram per milliliter and 100 milligram per milliliter. 
     
     
         6 . The method of  claim 1 , wherein the first defensin is present in the topical formulation at a concentration between 1 and 30 ng/ml. 
     
     
         7 . The method of  claim 1 , wherein the first defensin is encapsulated in a liposome or nanoparticle. 
     
     
         8 . The method of  claim 8 , wherein the first defensin is associated with a protein carrier. 
     
     
         9 . The method of  claim 10 , wherein the protein carrier comprises human serum albumin, recombinant albumin, bovine serum albumin, or egg albumin. 
     
     
         10 . The method of  claim 1 , wherein the topical formulation further comprises a supplement for LGR6+ stem cells, wherein the supplement comprises human serum albumin, bovine serum albumin, egg albumin, plant hydrolysate, beta-cyclodextrin, glutamine, phospholipids, fibronectin, hyaluronate, plant hydrolysate, L-alanyl-Lglutamine, gelatin, vitamin E, recombinant albumin, hyaluronic acid, epidermal growth factor, fibroblast growth factor, recombinant gelatin, Tocopheryl Nicotinate, Coenzyme Q10, 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 offincinalis seed oil, tocopheryl, saccharomyces lysate extract, carrageenan, or phenoxyethanol. 
     
     
         11 . The method of  claim 1 , wherein the first defensin comprises alpha-defensin 5 or beta-defensin 3. 
     
     
         12 . The method of  claim 1 , wherein the topical formulation further comprises a second defensin. 
     
     
         13 . The method of  claim 12 , wherein the second defensin is different from the first defensin, and wherein the second defensin is present in the topical formulation at a sub-antimicrobially effective concentration. 
     
     
         14 . The method of  claim 12 , wherein the second defensin comprises a synthetic defensin, a human defensin, recombinant 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. 
     
     
         15 . The method of  claim 12 , wherein the second 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. 
     
     
         16 . The method of  claim 12 , wherein the second defensin is present in the topical formulation at a concentration between 1 picogram per milliliter and 100 milligram per milliliter. 
     
     
         17 . The method of  claim 12 , wherein the second defensin is present in the topical formulation at a concentration between 1 and 30 ng/ml. 
     
     
         18 . The method of  claim 1 , wherein the subject has a skin condition, and wherein the skin condition comprises a decrease in skin hydration, a decrease in skin elasticity, a decrease in skin extensibility, a decrease in skin firmness, skin laxity, skin aging, skin thinning, or a decrease in a barrier property of skin. 
     
     
         19 . The method of  claim 1 , wherein the applying the topical formulation is effective to activate an inflammatory pathway, activate a wound healing pathway, stimulate LGR6+ cell activation, recruit stem cells to replace depleted interfollicular epidermis stem cells, increase the number of interfollicular epidermal stem cells, increase the number of epidermal cells, prevent water loss in skin, improve tight junctions of epithelial cells, stimulate cell migration, stimulate skin collagen structure, reconstruct skin collagen structure, stimulate cell redistribution in an affected area and surrounded tissues, inhibit apoptosis, stimulate angiogenesis, stimulate chemotaxis, stimulate an immune response, or stimulate repair of a cell membrane. 
     
     
         20 . The method of  claim 1 , wherein the subject has psoriasis, eczema, acne, EGRF inhibitor related cutaneous skin toxicities, or sun burned skin.