Microcapsules comprising liver cells and erythropoietin, methods for preparing said microcapsules and methods for treating a patient comprising applying said microcapsules to the patient

Abstract

Microcapsules containing a capsule shell encapsulating a suspension of a therapeutically effective amount of liver cells in physical contact to a liver cell stimulating amount of erythropoietin.

1 . A microcapsule comprising a capsule shell encapsulating a suspension of a therapeutically effective amount of liver cells in physical contact to a liver cell stimulating amount of erythropoietin. 
     
     
         2 . The microcapsule according to  claim 1 , wherein the liver cells are selected from the group consisting of hepatic precursor cells, hepatic stem cells, hepatoblasts and hepatocytes. 
     
     
         3 . The microcapsule according to  claim 1 , wherein the liver cells are obtained from adult liver, embryogenic liver, fetal liver, neonatal liver or liver cell cultures. 
     
     
         4 . The microcapsule according to  claim 1 , wherein the liver cells are human liver cells, non-human primate liver cells, pig liver cells, dog liver cells, cat liver cells, rabbit liver cells, mouse liver cells or rat liver cells. 
     
     
         5 . The microcapsule according to  claim 1 , wherein the microcapsules have an average diameter from 100 to 700 μm. 
     
     
         6 . The microcapsule according to  claim 1 , wherein the liver cells have an average diameter of 8 to 14 μm. 
     
     
         7 . The microcapsule according to  claim 1 , wherein the therapeutically effective amount of liver cells is from 10 4  to 10 8  liver cells/ml suspension. 
     
     
         8 . The microcapsule according to  claim 1 , wherein the liver cell stimulating amount of erythropoietin is 10 −7  to 10 −3  U/ml suspension. 
     
     
         9 . The microcapsule according to  claim 1 , wherein the erythropoietin is wild type erythropoietin or recombinant erythropoietin. 
     
     
         10 . The microcapsule according to  claim 1 , wherein the capsule shell is made from a biocompatible material being selected from the group consisting of alginate, alginate-chitosan (AC), alginate-poly-L-lysine (APA), thermogelation-polymer and PEG-hydrogel. 
     
     
         11 . The microcapsule according to  claim 1 , wherein in addition to the liver cells at least one further cell type is present in the microcapsule. 
     
     
         12 . The microcapsule according to  claim 1 , wherein the microcapsule is coated. 
     
     
         13 . The microcapsule according to  claim 1 , wherein the microcapsule contains a biocompatible matrix embedding the liver cells and the erythropoietin. 
     
     
         14 . A method for preparing the microcapsule according to  claim 1 , said method comprising
 d) providing a suspension of a therapeutically effect amount of liver cells and a liver cell stimulating amount of erythropoietin,   e) mixing the suspension of the liver cells and the erythropoietin to bring them in physical contact to each other and   f) encapsulating the suspension of the liver cells and the erythropoietin in a biocompatible capsule shell material so as to form the microcapsule.   
     
     
         15 . The method according to  claim 14 , wherein the microcapsules obtained in step c) are cryopreserved. 
     
     
         16 . A method for the prophylactic or therapeutic treatment of a liver disease in a subject in need thereof comprising administering the microcapsules according to  claim 1  to the subject in need thereof. 
     
     
         17 . The method according to  claim 16 , wherein the liver disease is hepatitis, cirrhosis, inborn errors of metabolism, acute liver failure, acute liver infections, acute chemical toxicity, chronic liver failure, cholangiocitis, biliary cirrhosis, Alagille syndrome, alpha-1-antitrypsin deficiency, autoimmune hepatitis, biliary atresia, cancer of the liver, cystic disease of the liver, fatty liver, galactosemia, gallstones, Gilbert's syndrome, hemochromatosis, hepatitis A, hepatitis B, hepatitis C and other hepatitis viral infections, poryphyria, primary sclerosing cholangitis, Reye's syndrome, sarcoidosis, tyrosinemia, type 1 glycogen storage disease or Wilson's disease. 
     
     
         18 . The method according to  claim 15 , wherein the administration is effected by introduction of the microcapsules under the liver capsule, into the spleen, into the liver, into the liver pulp or into the spleenic artery or portal vein. 
     
     
         19 . A method for introducing liver cells in a subject comprising administering the microcapsules according to  claim 1  into the subject. 
     
     
         20 . A method for cultivating liver cells in a culture medium comprising culturing microcapsules according to  claim 1  in a suitable culture medium.