Expandable cell populations from brain biopsies of living subjects

Abstract

The present invention relates to a method of producing expandable cultured brain cells. The brain cells are neurotrophic factor (NTF) positive. The expandable cultured brain cells are obtained by culturing a biopsy obtained from the cortical and/or subcortical brain region of a living subject. The biopsies can be obtained during neurosurgical procedures such as deep brain stimulation. The expandable cultured brain cells of the present invention are useful for the treatment of neurological diseases and other medical conditions.

1 . A cultured brain tissue-derived cell that is positive for at least one neurotrophic factor (NTF). 
     
     
         2 . The cultured brain tissue-derived cell of  claim 1 , wherein the cultured brain tissue-derived cell is further positive for at least one oligodendrogial protein. 
     
     
         3 . The cultured brain tissue-derived cell of  claim 1 , wherein the cultured brain tissue-derived cell is further positive for at least one progenitor marker. 
     
     
         4 . The cultured brain tissue-derived cell of  claim 1 , wherein the cultured brain tissue-derived cell is further positive for at least one mesenchymal protein. 
     
     
         5 . The cultured brain tissue-derived cell of  claim 1 , wherein the cultured brain tissue-derived cell is further positive for at least one oligodendrogial protein and for at least one progenitor marker. 
     
     
         6 . The cultured brain tissue-derived cell of  claim 1 , wherein the cultured brain tissue-derived cell is further positive for at least one oligodendrogial protein, for at least one progenitor marker and for at least one mesenchymal protein. 
     
     
         7 . The cultured brain tissue-derived cell of  claim 1 , wherein the at least one NTF include members of glial cell line-derived neurotrophic factor (GDNF) family of ligands (GFL), neurotrophin and CDNF/MANF families. 
     
     
         8 . The cultured brain tissue-derived cell of  claim 1 , wherein the cultured brain tissue-derived cell is genetically or physiologically modified to underexpress, express or overexpress a cellular molecule of interest. 
     
     
         9 . The cultured brain tissue-derived cell of  claim 1 , wherein said cultured brain tissue-derived cell is non-genetically modified. 
     
     
         10 . The cultured brain tissue-derived cell of  claim 1 , wherein the cultured brain tissue-derived cell is a research grade cell. 
     
     
         11 . The cultured brain tissue-derived cell of  claim 1 , wherein the cultured brain tissue-derived cell is obtained from a living subject. 
     
     
         12 . A method of producing expandable brain cells, the method comprising: (a) harvesting brain cells from a living subject, and (b) expanding the brain cells in a culturing medium thereby producing expanded brain cells. 
     
     
         13 . The method of  claim 12 , wherein the brain cells are obtained during a neurosurgical procedure of the living subject. 
     
     
         14 . The method of  claim 12 , wherein the expanded brain cells include cells which are positive for at least one neurotrophic factor (NTF). 
     
     
         15 . The method of  claim 14 , wherein the NTF includes one or more members of glial cell line-derived neurotrophic factor (GDNF) family of ligands (GFL), neurotrophin and CDNF/MANF families. 
     
     
         16 . The method of  claim 12 , wherein the expanded brain cells include cells which are further positive for at least one oligodendrogial protein. 
     
     
         17 . The method of  claim 12 , wherein the expanded brain cells include cells which are further positive at least one oligodendrogial protein and at least one progenitor marker. 
     
     
         18 . The method of  claim 12 , wherein the expanded brain cells include cells which are further positive for at least one oligodendrogial protein, at least one progenitor marker and at least one mesenchymal protein. 
     
     
         19 . The method of  claim 12 , wherein the method further comprises genetically or physiologically manipulating the expanded brain cell to underexpress, express or overexpress a molecule of interest. 
     
     
         20 . The method of  claim 12 , wherein step (b) comprises: (i) culturing the brain cells in a growth medium, and (ii) passaging the cultures of brain cells. 
     
     
         21 . The method of  claim 12  wherein the brain cells are produced for in vitro research purposes. 
     
     
         22 . The method of  claim 12 , wherein the expanded brain cells are produced for the treatment of a neurological disorder or other medical condition in a subject. 
     
     
         23 . The method of  claim 22 , wherein the expanded brain cells are autologous to the subject. 
     
     
         24 . A method of treating a neurological disorder in a subject, the method comprising: (a) expanding brain cells; and (b) administering an effective amount of the expanded brain cells to the subject, wherein the expanded brain cells promote treatment of the neurological disorder. 
     
     
         25 . The method of  claim 24 , wherein the method further comprises culturing the brain cells in a culture medium such that the cultured brain cells are non-immunogenic when administered. 
     
     
         26 . The method of  claim 25 , wherein the culture medium includes brain tissue. 
     
     
         27 . The method of  claim 24 , wherein the brain cells are obtained during a neurosurgical procedure. 
     
     
         28 . The method of  claim 24 , wherein the expanded brain cells include cells which are positive for at least one neurotrophic factor (NTF). 
     
     
         29 . The method of  claim 28 , wherein the NTF includes one or more members of glial cell line-derived neurotrophic factor (GDNF) family of ligands (GFL), neurotrophin and CDNF/MANF families. 
     
     
         30 . The method of  claim 24 , wherein the expanded brain cells include cells which are further positive for at least one oligodendrogial protein. 
     
     
         31 . The method of  claim 24 , wherein the expanded brain cells include cells which are further positive at east one oligodendrogial protein and at least one progenitor marker. 
     
     
         32 . The method of  claim 24 , wherein the expanded brain cells include cells which are further positive for at least one oligodendrogial protein, at least one progenitor marker and at least one mesenchymal protein. 
     
     
         33 . The method of  claim 24 , wherein the method further comprises genetically or physiologically manipulating the expanded brain cell. 
     
     
         34 . The method of  claim 24 , wherein step (a) comprises: (i) harvesting brain cells from a living subject; (ii) culturing the brain cells in a growth medium, and (iii) passaging the cultures of brain cells. 
     
     
         35 . The method of  claim 24 , wherein the brain cells are autologous to the subject. 
     
     
         36 . The method of  claim 24 , wherein the brain cells are administered intravenous, intramuscular, intraluminal, intratracheal, intraperitoneal, subcutaneous, intracerebrally, intraventricular or intrathecally. 
     
     
         37 . (canceled) 
     
     
         38 . (canceled) 
     
     
         39 . (canceled) 
     
     
         40 . (canceled) 
     
     
         41 . (canceled) 
     
     
         42 . (canceled) 
     
     
         43 . (canceled) 
     
     
         44 . A method for selecting brain cultured cells for a desired cellular molecule, the method comprising: harvesting brain cells from the brain of a living subject, culturing the harvested brain cells to obtain a culture of expandable brain cells, assaying the expandable cells for the desired cellular molecule, and selecting the expandable brain cells pursuant to said assay. 
     
     
         45 . The method of  claim 44 , wherein the desired marker is selected from one or more of: a neurotrophic factor (NTF), an oligodendrogial protein, a progenitor marker, a mesenchymal protein. 
     
     
         46 . (canceled) 
     
     
         47 . (canceled) 
     
     
         48 . (canceled) 
     
     
         49 . (canceled) 
     
     
         50 . (canceled) 
     
     
         51 . (canceled) 
     
     
         52 . (canceled) 
     
     
         53 . (canceled) 
     
     
         54 . (canceled) 
     
     
         55 . A composition comprising the brain tissue-derived cell or cells of the present invention and a carrier. 
     
     
         56 . The composition of  claim 55 , wherein the composition further includes brain tissue. 
     
     
         57 . (canceled) 
     
     
         58 . (canceled) 
     
     
         59 . (canceled) 
     
     
         60 . (canceled) 
     
     
         61 . The cultured brain-tissue derived cell of  claim 1 , wherein the cultured brain tissue-derived cell is obtained from a subject having Parkinson's disease. 
     
     
         62 . The method of  claim 24 , the neurological disorder is Parkinson's disease, the expanded brain cells are positive for at least one neurotrophic factor, and wherein the brain cells are obtained from the brain of the subject, or from the living brain of a patient with Parkinson's disease.