Composition derived from stem cell released molecules & methods for formulation thereof

Abstract

Compositions for use in treatment of a variety of tissue diseases include stem cells and stem cell released molecules (SRM's) suspended in an aqueous solution with a cellulosic material or other thickening agent. The stem cells and SRM's can be derived from one or more distinct cell lines. The SRM's can further include one or more mucins, cytokines, or growth factors. Exemplary formulations include stem cells and SRMs derived from epithelial stem cells, corneal limbal stem cells, and fibroblasts. Other compositions and methods for formulation thereof are described.

1 . A therapeutic composition for hair growth treatment, comprising:
 an amount of stem cells and stem cell released molecules derived from a first cell line collectively defining a first adjuvant material, wherein said first cell line comprises one of: mesenchymal stem cells, epithelial stem cells, limbal stem cells, or fibroblasts;   an amount of stem cells and stem cell released molecules derived from a second cell line and a third cell line collectively defining a second adjuvant material, wherein said second or third cell line each comprises one of: mesenchymal stem cells, epithelial stem cells, limbal stem cells, or fibroblasts, and wherein each of said second cell line said third cell line is distinct from said first cell line; and   a thickening agent comprising at least one of a cellulosic material or a polymer;   said first adjuvant material, second adjuvant material, and thickening agent being combined in an aqueous solution.   
     
     
         2 . The composition of  claim 1 , wherein said stem cell released molecules comprise at least one of: cytokines, anti-oxidants, micro-RNA, growth factors, and mucins. 
     
     
         3 . The composition of  claim 2 , wherein said cytokines include one or more of: interleukin (IL)-2, IL-4, IL-5, IL-6, IL-10, interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, and IL-1 beta. 
     
     
         4 . The composition of  claim 2 , wherein said growth factors include one or more of: keratinocyte growth factor (KGF), hepatocyte growth factor (HGF), epidermal growth factor (EGF), and transforming growth factor (TGF). 
     
     
         5 . The composition of  claim 2 , wherein said mucins include one or more of: MUC1, MUC2, MUC4, MUC7, MUC16, and MUC5AC. 
     
     
         6 . The composition of  claim 1 , wherein said cellulosic material comprises one or more of: methyl cellulose, sodium carboxymethyl cellulose, and hydroxypropylmethyl cellulose. 
     
     
         7 . The composition of  claim 1 , wherein said polymer comprises one or more of: carboxyvinyl polymer, polyvinyl alcohol, polyvinyl pyrrolidone, polyethylene glycol, and polysorbate  80 . 
     
     
         8 . The composition of  claim 1 , comprising: Osteonectin, decorin, collagens I, III, IV, V, fibronectin, fibrillin, laminins, and hyaluronic acid. 
     
     
         9 . The composition of  claim 1 , comprising: HLA-A, -B, and -C, exosomes, MSC IL-6, M-CSF, PGE2, IDO, TGF-, HLA-G, and PGE2, IL-1, IL-6, GDNF, BDNF, IGF-1, VEGF, GDNF, NGF, bFGF, BMP-4, bFGF, VEGF, PDGF, IL-1β, IL-10, stem cell-derived factor-(SDF-) 1, HGF, IGF-1, thymosin-β4, and Wnt5a, IL-1β and TNF-α, bFGF, HGF, angiopoietin-1 and -2 (Ang-1 and -2), cysteine-rich protein 61, antioxidants, proteasomes. 
     
     
         10 . The composition of  claim 1 , comprising: Wnt and Bmp, SOX2, beta-catenin. 
     
     
         11 . A therapeutic composition, comprising:
 a first adjuvant material comprising at least one of: stem cells and stem cell released molecules, said stem cells and said stem cell released molecules of said first adjuvant material each being derived from a first stem cell line;   a second adjuvant material comprising at least one of: stem cells and stem cell released molecules, said stem cells and said stem cell released molecules of said second adjuvant material each being derived from a second stem cell line; and   a thickening agent;   wherein said first stem cell line is distinct from said second stem cell line.   
     
     
         12 . A method for forming a therapeutic composition for hair growth treatment, comprising in any order the steps of:
 providing an amount of first stem cells;   culturing said first stem cells in vitro such that said first stem cells secrete one or more stem cell released molecules;   introducing a thickening agent; and   suspending said stem cells, stem cell released molecules, and thickening agent in an aqueous solution.   
     
     
         13 . The method of  claim 12 , further comprising the steps:
 providing an amount of second stem cells, said second stem cells being distinct from said first stem cells;   culturing said second stem cells in vitro such that said first stem cells secrete one or more stem cell released molecules; and   combining said first and second stem cells and stem cell released molecules.   
     
     
         14 . The method of  claim 13 , wherein each of said first and second stem cell is cultured only through early passage.