Oral delivery of therapeutic mammalian cells

Abstract

Described herein are oral delivery systems for use in delivering live mammalian cells to the intestinal tract of an individual.

1 . A composition of live mammalian cells formulated for oral delivery to an individual, the composition comprising (a) a matrix comprising about 0.5% to about 1.0% methyl cellulose and about 0.5% to about 1.0% alginate gel, and (b) a plurality of live mammalian cells, wherein the plurality of live mammalian cells is suspended in the matrix. 
     
     
         2 . The composition of  claim 1 , wherein the matrix comprises about 0.6% to about 0.9% methylcellulose and about 0.6% to about 0.9% alginate gel. 
     
     
         3 . The composition of  claim 2 , wherein the matrix comprises about 0.7% methylcellulose and about 0.7% alginate gel. 
     
     
         4 . The composition of  claim 1 , wherein the methyl cellulose and alginate gel are present at a ratio of about 1:1. 
     
     
         5 . (canceled) 
     
     
         6 . (canceled) 
     
     
         7 . The composition of  claim 1 , wherein the plurality of live mammalian cells comprises at least about 10,000 million live cells. 
     
     
         8 . The composition of  claim 1 , wherein the plurality of live mammalian cells comprises human cells. 
     
     
         9 . The composition of  claim 1 , wherein the plurality of live mammalian cells comprises non-human cells. 
     
     
         10 . The composition of  claim 9 , wherein the non-human animal cells are selected from canine cells, bovine cells, feline cells, porcine cells, equine cells, or ovine cells. 
     
     
         11 . The composition of  claim 1 , wherein the plurality of live mammalian cells comprises at least two types of cells. 
     
     
         12 . The composition of  claim 1 , wherein the plurality of live mammalian cells comprises multipotent cells. 
     
     
         13 . The composition of  claim 12 , wherein the multipotent cells comprise embryonic stem cells, pluripotent stem cells, induced pluripotent stem cells, mesenchymal stem cells, hematopoietic stem cells, myoblasts, fibroblasts, hepatic stem cells, kidney stem cells, heart stem cells, or intestinal stem cells. 
     
     
         14 . The composition of  claim 13 , wherein the multipotent cells comprise mesenchymal stem cells. 
     
     
         15 . The composition of  claim 14 , wherein the mesenchymal stem cells are Type 1 mesenchymal stem cells. 
     
     
         16 . The composition of  claim 14 , wherein the mesenchymal stem cells are Type 2 mesenchymal stem cells. 
     
     
         17 . The composition of  claim 1 , wherein the plurality of live mammalian cells comprise immune cells. 
     
     
         18 . The composition of  claim 17 , wherein the immune cells comprise B cells, T cells, CD8+ T cells, CD4+ T cells, NK cells, dendritic cells, or macrophage cells. 
     
     
         19 . The composition of  claim 1 , wherein the composition preserves the viability of the plurality of live mammalian cells above about 80% viability for at least 14 days at 24° C. 
     
     
         20 . The composition of  claim 1 , wherein the matrix further comprises an extracellular matrix protein. 
     
     
         21 . The composition of  claim 17 , wherein the extracellular matrix protein comprises collagen. 
     
     
         22 .- 28 . (canceled) 
     
     
         29 . A method of treating an inflammatory or autoimmune disorder in an individual comprising administering a dose of the composition of  claim 1  to the alimentary canal of an individual. 
     
     
         30 . The method of  claim 29 , wherein the individual is a human individual. 
     
     
         31 . The method of  claim 29 , wherein the individual is a dog, a cow, a cat, a pig, a horse, or a sheep. 
     
     
         32 . The method of  claim 29 , wherein the inflammatory or autoimmune disorder is a gastrointestinal inflammatory or autoimmune disorder. 
     
     
         33 . The method of  claim 29 , wherein the gastrointestinal inflammatory or autoimmune disorder comprises inflammatory bowel disease or Crohn's disease. 
     
     
         34 . The method of  claim 29 , wherein the gastrointestinal inflammatory or autoimmune disorder comprises Crohn's disease. 
     
     
         35 . A method of making the composition of live mammalian cells formulated for oral delivery of  claim 1 , the method comprising admixing a plurality of live mammalian cells with a matrix comprising about 0.5% to about 1.0% methyl cellulose and about 0.5% to about 1.0% alginate gel to provide a cell-matrix, and applying an enteric coating to cell-matrix. 
     
     
         36 .- 42 . (canceled)