Methods of treating an ischemic disease

Abstract

Methods of treating an ischemic disease in a subject are provided. Accordingly there is provided a method comprising administering to the subject a therapeutically effective amount of cells with reduced level of expression and/or activity of TNFR1, thereby treating the ischemic disease in the subject. Also provided is a method comprising treating with TNFalpha cells with reduced expression and/or activity of TNFR1 and administering to the subject a therapeutically effective amount of said cells, thereby treating the ischemic disease in the subject.

What is claimed is: 
     
         1 . A method of producing mononuclear bone marrow cells (mnBMCs) having reduced level of expression of TNFR1, the method comprising contacting ex-vivo or in-vitro mnBMCs comprising mesenchymal stem cells (MSCs) and lymphocytes or progenitors thereof with a nucleic acid agent which downregulates expression of TNFR1, thereby producing the mnBMCs having reduced level of expression of TNFR1. 
     
     
         2 . The method of  claim 1 , wherein said mnBMCs are obtained from bone marrow, peripheral blood or umbilical cord blood. 
     
     
         3 . The method of  claim 1 , wherein said agent does not downregulate expression of TNFR2. 
     
     
         4 . The method of  claim 1 , wherein said nucleic acid agent is an RNA agent. 
     
     
         5 . The method of  claim 1 , wherein said agent is a genome editing agent. 
     
     
         6 . The method of  claim 1 , wherein said agent in an RNA silencing agent. 
     
     
         7 . The method of  claim 1 , wherein said agent is selected from the group consisting of CRISPR/Cas system, a Zinc finger nuclease (ZFN), transcription-activator like effector nuclease (TALEN), meganuclease, antisense and siRNA. 
     
     
         8 . The method of  claim 1 , wherein said agent comprises a CRISPR/Cas system. 
     
     
         9 . The method of  claim 1 , wherein said nucleic acid agent comprises a nucleic acid sequence selected from the group consisting of SEQ ID NO: 18, 21, 24, 27, 30, 33, 36, 39, 42 and 45. 
     
     
         10 . The method of  claim 1 , comprising cryopreserving said cells following said contacting. 
     
     
         11 . The method of  claim 1 , further comprising contacting ex-vivo or in-vitro said cells with TNFα. 
     
     
         12 . The method of  claim 11 , wherein said contacting with said nucleic acid agent is effected prior to said contacting with said TNFα. 
     
     
         13 . The method of  claim 1 , comprising cryopreserving said cells following said contacting with said nucleic acid agent and prior to said contacting with said TNFα.