Genetically modified mesenchymal stem cell expressing Klotho
A genetically modified mesenchymal stem cell including an exogenous nucleic acid including 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. Also disclosed are methods of treating a patient including administering a therapeutically effective number of the genetically modified mesenchymal stem cells to the patient. The methods of treatment include treating the patient for a neurodegenerative disease; cancer; organ fibrosis; renal disease; age-related changes of organs or organ systems; to slow, reverse and/or inhibit aging; arteriosclerosis; dementia; diabetes mellitus; erectile dysfunction; autoimmune diseases or autoimmune-related diseases; an inflammatory disease of the lung and sepsis.
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 protein expression and secretion 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 3 , wherein the constitutive promoter is the EFS, PGK or EF1alpha promoter.
5 . 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.
6 . The genetically modified cell according to claim 1 , wherein the Klotho encoding region encodes for a secreted form of the Klotho protein.
7 . The genetically modified cell according to claim 6 , wherein the secreted form of 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.
8 . The genetically modified cell according to claim 1 , wherein the cell is a CD34 negative, self-renewing, multipotent mesenchymal stem cell, capable of adipogenic and osteogenic differentiation.
9 . A method of treating a medical condition that will therapeutically benefit from administration of Klotho protein in a patient, the method comprising administering to the patient a therapeutically effective number of genetically modified mesenchymal stem cells according to claim 1 that express and secrete Klotho protein.
10 . The method according to claim 9 , wherein said therapeutically effective number of genetically modified mesenchymal stem cells is administered subcutaneously.
11 . The method according to claim 9 , wherein said therapeutically effective number of genetically modified mesenchymal stem cells is administered intrathecally.
12 . The method according to claim 8 , wherein the patient is treated for a neurodegenerative disease.
13 . The method according to claim 9 , wherein the patient is treated for cancer.
14 . The method according to claim 9 , wherein the patient is treated for organ fibrosis.
15 . The method according to claim 9 , wherein the patient is treated for renal disease.
16 . The method according to claim 9 , wherein the patient is treated for age-related changes of organs or organ systems.
17 . The method according to claim 9 , wherein the patient is treated to slow, reverse and/or inhibit ageing.
18 . The method according to claim 9 , wherein the patient is treated for arteriosclerosis.
19 . The method according to claim 9 , wherein the patient is treated for dementia.
20 . The method according to claim 9 , wherein the patient is treated for diabetes mellitus.
21 . The method according to claim 9 , wherein the patient is treated for erectile dysfunction.
22 . The method according to claim 9 , wherein the patient is treated for autoimmune diseases or autoimmune-related diseases.
23 . The method according to claim 9 , wherein the patient is treated for an inflammatory disease of the lung.
24 . The method according to claim 9 , wherein the patient is treated for sepsis.
25 . The method according to claim 9 , wherein the genetically modified mesenchymal stem cells are CD34 negative, self-renewing, multipotent mesenchymal stem cells, capable of adipogenic and osteogenic differentiation.