Method and kit for providing an increased expression of telomerase, brain-derived neurotrophic factor, stromal cell-derived factor-1, cxc chemokine receptor 4, and/or immune regulatory factor of stem cell

Abstract

A method for providing an increased expression of at least one of telomerase, brain-derived neurotrophic factor (BDNF), stromal cell-derived factor-1 (SDF1), CXC chemokine receptor 4 (CXCR4), and an immune regulatory factor of a stem cell in a subject is provided. The method comprises simultaneously or separately administering to the subject an effective amount of (a) a phthalide and (b) a stem cell.

What is claimed is: 
     
         1 . A method for providing an increased expression of at least one of telomerase, brain-derived neurotrophic factor (BDNF), stromal cell-derived factor-1 (SDF1), CXC chemokine receptor 4 (CXCR4), and an immune regulatory factor of a stem cell in a subject, comprising simultaneously or separately administering to the subject an effective amount of (a) a phthalide and (b) a stem cell, wherein said increased expression is increased in comparison with a corresponding expression of the effective amount of the stem cell in a subject without being administered with a phthalide. 
     
     
         2 . The method as claimed in  claim 1 , wherein the phthalide is selected from the group consisting of n-butylidenephthalide (BP), a structural analogue of BP, a pharmaceutically acceptable salt of a structural analogue of BP, a pharmaceutically acceptable ester of a structural analogue of BP, and combinations thereof. 
     
     
         3 . The method as claimed in  claim 2 , wherein the structural analogue of n-butylidenephthalide is 3-butylidene-4,5-dihydrophthalide (ligustilide). 
     
     
         4 . The method as claimed in  claim 1 , wherein the phthalide is selected from the group consisting of a compound of formula (I), a pharmaceutically acceptable salt of the compound of formula (I), a pharmaceutically acceptable ester of the compound of formula (I), and combinations thereof: 
       
         
           
           
               
               
           
         
         wherein, A is a C1-C5 hydrocarbyl being optionally substituted by one or more substituents selected from the group consisting of —OH, ═O, and C1-C3 hydrocarbyl; 
         X is H, -C 
       
       
         
           
           
               
               
           
         
          R 1  is H or a substituted or unsubstituted C1-C20 hydrocarbyl, wherein one or more —CH 2 — in the hydrocarbyl are optionally replaced by —NH— or —O—; Y is O or S and optionally bonds with A to form a five-membered ring, with a proviso that when Y bonds with A to form a five-membered ring, R 1  is not present. 
       
     
     
         5 . The method as claimed in  claim 4 , wherein A is a C1-C5 alkyl or alkenyl being optionally substituted by one or more substituents selected from the group consisting of —OH, ═O, and C1-C3 alkyl; and R 1  is H or a substituted or unsubstituted C1-C10 hydrocarbyl, wherein one or more —CH 2 — in the hydrocarbyl are optionally replaced by —NH— or —O—. 
     
     
         6 . The method as claimed in  claim 4 , wherein A is 
       
         
           
           
               
               
           
         
       
       and R 1  is H, 
       
         
           
           
               
               
           
         
       
     
     
         7 . The method as claimed in  claim 1 , wherein the phthalide is selected from the group consisting of the following compounds: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         and combinations thereof. 
       
     
     
         8 . The method as claimed in  claim 1 , wherein the phthalide is n-butylidenephthalide (BP). 
     
     
         9 . The method as claimed in  claim 1 , wherein the stem cell is selected from the group consisting of an embryonic stem cell, an adult stem cell, an induced pluripotent stem cell, and combinations thereof. 
     
     
         10 . The method as claimed in  claim 1 , wherein the stem cell is selected from the group consisting of a mesenchymal stem cell, a hematopoietic stem cell, and combinations thereof. 
     
     
         11 . The method as claimed in  claim 10 , wherein the stem cell is a mesenchymal stem cell and selected from the group consisting of a bone marrow stem cell, an umbilical cord blood stem cell, a placenta stem cell, an adipose stem cell, an oral stem cell, an olfactory bulbs stem cell, an amniotic fluid stem cell, an amniotic stem cell, an umbilical cord stem cell, an umbilical cord lining stem cell, and combinations thereof. 
     
     
         12 . The method as claimed in  claim 11 , wherein the stem cell is an adipose stem cell. 
     
     
         13 . The method as claimed in  claim 1 , wherein the method is for at least one of inhibiting the apoptosis of motor neurons, protecting motor neurons, and improving the proliferation of motor neurons in the subject. 
     
     
         14 . The method as claimed in  claim 1 , wherein the method is for at least one of treating a motor neuron degenerative disease and delaying the onset of a motor neuron degenerative disease. 
     
     
         15 . The method as claimed in  claim 14 , wherein the motor neuron degenerative disease is selected from the group consisting of amyotrophic lateral sclerosis, myasthenia gravis, myasthenia, muscular atrophy, muscular dystrophy, multiple sclerosis, multiple system atrophy, spinal muscular atrophy, and combinations thereof. 
     
     
         16 . The method as claimed in  claim 14 , wherein the motor neuron degenerative disease is amyotrophic lateral sclerosis. 
     
     
         17 . A kit, comprising:
 a first composition, comprising a phthalide; and   a second composition, comprising a stem cell;   wherein the first composition and the second composition are to be administered to a subject in need simultaneously or separately.   
     
     
         18 . The kit as claimed in  claim 17 , wherein the phthalide is as defined in  claim 2 . 
     
     
         19 . The kit as claimed in  claim 17 , wherein the stem cell is as defined in  claim 9 . 
     
     
         20 . The kit as claimed in  claim 17 , further comprises a third composition which comprises a solvent or a solution and can be mixed with the first composition and/or the second composition to provide a solution for injection. 
     
     
         21 . The kit as claimed  claim 17 , wherein the first composition is in a form for oral administration, nasal administration, corticospinal tract injection, intrathecal injection, intracerebral injection, intravenous injection, intraperitoneal injection, and/or subcutaneous injection; and the second composition is in a form for corticospinal tract injection, intrathecal injection, intracerebral injection, intravenous injection, intraperitoneal injection, and/or subcutaneous injection. 
     
     
         22 . A method for treating a motor neuron degenerative disease and/or delaying the onset of a motor neuron degenerative disease in a subject, comprising administering to the subject an effective amount of a metabolic precursor of a phthalide, wherein the metabolic precursor of a phthalide is 3-butylidene-4,5-dihydrophthalide (ligustilide). 
     
     
         23 . The method as claimed in  claim 22 , wherein the neuron degenerative disease is at least one of amyotrophic lateral sclerosis, myasthenia gravis, myasthenia, muscular atrophy, muscular dystrophy, multiple sclerosis, multiple system atrophy, and spinal muscular atrophy. 
     
     
         24 . The method as claimed in  claim 22 , wherein the neuron degenerative disease is amyotrophic lateral sclerosis.