Genetically modified mesenchymal stem cell expressing klotho

Abstract

A genetically modified mesenchymal stem cell (MSC) includes an exogenous nucleic acid that includes a Klotho encoding region operably linked to a promoter or promoter/enhancer combination. The MSCs can be used for the treatment of cancer, organ fibrosis, renal failure, age-related changes of organs or organ systems, arteriosclerosis, and neurodegenerative diseases, such as Alzheimer's disease (AD), Multiple sclerosis (MS), Huntington's disease, Amyotrophic Lateral Sclerosis (ALS), Parkinson's disease, and Schizophrenia, as well as dementia, diabetes mellitus, sepsis and autoimmune diseases and autoimmune-related diseases.

1 . A genetically modified mesenchymal stem cell comprising an exogenous nucleic acid comprising a Klotho-encoding region operably linked to a promoter or promoter/enhancer combination, wherein the genetically modified mesenchymal stem cell exhibits increased Klotho expression compared to an unmodified mesenchymal stem cell. 
     
     
         2 . The genetically modified cell according to  claim 1 , wherein the exogenous nucleic acid is comprised in a viral vector. 
     
     
         3 . The genetically modified cell according to  claim 1 , wherein the promoter is a constitutive promoter. 
     
     
         4 . The genetically modified cell according to  claim 1 , wherein the constitutive promoter is the EFS, PGK or EF1alpha promoter. 
     
     
         5 .- 9 . (canceled) 
     
     
         10 . The genetically modified cell according to  claim 1 , wherein the Klotho encoding region encodes a protein according to one of SEQ ID NO 6 to 10, or wherein the Klotho encoding region comprises or consists of a sequence according to SEQ ID NO 1 to 5. 
     
     
         11 . The genetically modified cell according to  claim 1 , wherein the Klotho encoding region encodes for a secreted form of the Klotho protein. 
     
     
         12 . (canceled) 
     
     
         13 . The genetically modified cell according to  claim 1 , wherein the secreted form the Klotho protein possess an amino acid sequence with an identity of at least 80% to SEQ ID NO 8, or an amino acid sequence according to SEQ ID NO 8. 
     
     
         14 . (canceled) 
     
     
         15 . A method of treating a patient comprising introducing a therapeutically effective number of genetically modified cells according to  claim 1  into the bloodstream of the patient. 
     
     
         16 . The method according to  claim 15 , wherein said therapeutically effective number of genetically modified cells is introduced subcutaneously. 
     
     
         17 . The method according to  claim 15 , wherein said therapeutically effective number of genetically modified cells is administered intrathecally. 
     
     
         18 . (canceled) 
     
     
         19 . The method according to  claim 15 , wherein the patient is treated for a neurodegenerative disease. 
     
     
         20 . The method according to  claim 15 , wherein the patient is treated for cancer. 
     
     
         21 . The method according to  claim 15 , wherein the patient is treated for organ fibrosis. 
     
     
         22 . The method according to  claim 15 , wherein the patient is treated for renal disease. 
     
     
         23 . The method according to  claim 22 , wherein the Klotho encoding region encodes for a secreted form of the Klotho protein, and the genetically modified mesenchymal stem cell exhibits increased expression of said secreted from of Klotho protein compared to an unmodified mesenchymal stem cell. 
     
     
         24 . The method according to  claim 15 , wherein the patient is treated for age-related changes of organs or organ systems. 
     
     
         25 . The method according to  claim 15 , wherein the patient is treated to slow, reverse and/or inhibit ageing. 
     
     
         26 . The method according to  claim 15 , wherein the patient is treated for arteriosclerosis. 
     
     
         27 . The method according to  claim 15 , wherein the patient is treated for dementia. 
     
     
         28 . The method according to  claim 15 , wherein the patient is treated for diabetes mellitus. 
     
     
         29 . The method according to  claim 15 , wherein the patient is treated for erectile dysfunction. 
     
     
         30 . The method according to  claim 15 , wherein the patient is treated for autoimmune diseases or autoimmune-related diseases. 
     
     
         31 . The method according to  claim 15 , wherein the patient is treated for an inflammatory disease of the lung. 
     
     
         32 . The method according to  claim 15 , wherein the patient is treated for sepsis. 
     
     
         33 .- 39 . (canceled)