Biocompatible Sculptured Extracellular Nanomatrix enables self assembly of neural stem cells into miniature brain organoids of substantia nigra

Abstract

The present invention provides substantia nigra organoids on silica iSECnMs and method of producing the same. The present invention also provides method of cell therapy including the substantia nigra organoids on silica iSECnMs. It also provides a method of promoting differentiation of neural stem cells to neurons includes culturing the neural stem cells on a nanostructure having a plurality of nanozigzags or nanohelices fabricated from SiO 2 or TiO x .

1 . A method of promoting differentiation of neural stem cells to neurons in the comprising culturing the neural stem cells on a nanostructure having a plurality of nanozigzags or nanohelices fabricated from SiO 2  or TiO x , and wherein x is in the range of 0.33≤x≤2. 
     
     
         2 . The method of  claim 1 , wherein the culturing is performed in the absence of growth factor. 
     
     
         3 . The method of  claim 1 , wherein the neurons comprise dopaminergic neurons, GABAergic neurons or glutamatergic neurons. 
     
     
         4 . The method of  claim 1 , wherein the nanostructure includes nanozigzags and the nanozigzags have a pitch of 80 nm to 250 nm. 
     
     
         5 . The method of  claim 4 , wherein the nanozigzags have a contact depth of 90 nm to 260 nm. 
     
     
         6 . The method of  claim 1 , wherein the nanostructure includes nanozigzags and a length of each nanozigzag is at least 550 nm and each nanozigzag comprises at least three pitches and having a pitch of at least 165 nm. 
     
     
         7 . The method of  claim 1 , wherein the neural stem cells form a substantis nigra organoid. 
     
     
         8 . A method for inducing proliferation and differentiation of stem cells comprising comprises culturing the stem cells on a nanostructure in the absence of chemical growth factors, the nanostructure comprising a plurality of nanohelices or nanozigzags, wherein the plurality of nanohelices or nanozigzags are made of SiO 2  or TiO x , and wherein x is in the range of 0.33≤x≤2. 
     
     
         9 . The method according to  claim 8 , wherein said stem cells are neural stem cells 
     
     
         10 . The method according to  claim 8 , wherein the nanostructure comprises a plurality of nanozigzags, and a length of each of nanozigzag is at least 550 nm and each nanozigzag comprises at least three pitches and having a pitch of at least 165 nm. 
     
     
         11 . The method according to  claim 8 , wherein the nanostructure comprises a plurality of nanozigzags having a stiffness of 19.7±2.3 μN/nm. 
     
     
         12 . The method of  claim 8 , wherein the nanostructure includes nanozigzags and the nanozigzags have a pitch of 80 nm to 250 nm. 
     
     
         13 . The method of  claim 12 , wherein the nanozigzags have a contact depth of 90 nm to 260 nm. 
     
     
         14 . The method of  claim 8 , wherein the stem cells are cultured for 14 days or more. 
     
     
         15 . The method of  claim 1 , where the nanostructure comprises a plurality of nanohelices, each nanohelix having a length of at least approximately 540 nm and a pitch of at least 240 nm. 
     
     
         16 . The method of  claim 8 , where the nanostructure comprises a plurality of nanohelices, each nanohelix having a length of at least approximately 540 nm and a pitch of at least 240 nm.