Human cord blood as a source of neural tissue repair of the brain and spinal cord

Abstract

The present invention relates to the use of umbilical cord blood cells from a donor or patient to provide neural cells which may be used in transplantation. The isolated cells according to the present invention may be used to effect autologous and allogeneic transplantation and repair of neural tissue, in particular, tissue of the brain and spinal cord and to treat neurodegenerative diseases of the brain and spinal cord.

What is claimed is: 
     
         1 . Neural cells obtained by exposing pluripotent stem or progenitor cells obtained from umbilical cord blood to an amount of a differentiation agent effective for changing a phenotype of the stem or progenitor cells to a neural phenotype. 
     
     
         2 . The neural cells of  claim 1 , wherein the differentiation agent is selected from the group consisting of retinoic acid, fetal or mature neuronal cells, BDNF, GDNF, NGF, FGF, TGF, CNTF, BMP, LIF, GGF, THF, IGF, CSF, KIT-SCF, interferon, triiodothyronine, thyroxine, erythropoietin, thrombopoietin, silencers, SHC, neuroproteins, proteoglycans, glycoproteins, neural adhesion molecules, cell signaling molecules and mixtures thereof. 
     
     
         3 . The neural cells of  claim 1 , wherein the differentiation agent is a mixture of retinoic acid and NGF. 
     
     
         4 . A method of producing neural cells from umbilical cord blood comprising:
 (a) obtaining a sample of mononuclear cells from the umbilical cord blood; and   (b) growing the mononuclear cells from step (a) in a culture medium containing an effective amount of a differentiation agent for a period sufficient to change a phenotype of the stem or progenitor cells to a neural phenotype.   
     
     
         5 . The method of  claim 4 , wherein the differentiation agent is selected from the group consisting of retinoic acid, fetal or mature neuronal cells, BDNF, GDNF, NGF, FGF, TGF, CNTF, BMP, LIF, GGF, THF, IGF, CSF, KIT-SCF, interferon, triiodothyronine, thyroxine, erythropoietin, thrombopoietin, silencers, SHC, neuroproteins, proteoglycans, glycoproteins, neural adhesion molecules, cell signaling molecules and mixtures thereof. 
     
     
         6 . The method of  claim 4 , wherein the differentiation agent is a mixture of retinoic acid and NGF. 
     
     
         7 . The method of  claim 5 , wherein the neuronal cells are selected from the group consisting of mesencephalic cells and striatal cells. 
     
     
         8 . A method of producing neural cells from umbilical cord blood comprising:
 (a) obtaining a sample of mononuclear cells from the umbilical cord blood;   (b) selecting for and isolating a sample of pluripotent stem or progenitor cells within the sample; and   (c) growing the stem or progenitor cells from step (b) in a culture medium containing an effective amount of a differentiation agent for a period sufficient to change a phenotype of the stem or progenitor cells to a neural phenotype.   
     
     
         9 . The method of  claim 8 , wherein the selecting and isolating step (b) is carried out using a magnetic cell separator to separate out cells containing a CD marker. 
     
     
         10 . The method of  claim 8 , wherein the differentiation agent is selected from the group consisting of retinoic acid, fetal or mature neuronal cells, BDNF, GDNF, NGF, FGF, TGF, CNTF, BMP, LIF, GGF, THF, IGF, CSF, KIT-SCF, interferon, triiodothyronine, thyroxine, erythropoietin, thrombopoietin, silencers, SHC, neuroproteins, proteoglycans, glycoproteins, neural adhesion molecules, cell signaling molecules and mixtures thereof. 
     
     
         11 . The method of  claim 10 , wherein the retinoic acid is selected from 9-cis retinoic acid, all trans retinoic acid and mixtures thereof. 
     
     
         12 . The method of  claim 8 , further comprising:
 (a) subjecting the mononuclear cells to an amount of an anti-proliferating cell agent effective to eliminate essentially all proliferating cells from the mononuclear cell sample;   (b) exposing the remaining non-proliferating cells from step (a) to a mitogen to provide a population of differentiated cells and quiescent cells comprising a population of pluripotent stem or progenitor cells;   (c) growing the population of the differentiated cells and quiescent cells from step (b) to selectively grow the quiescent cells to an essential exclusion of differentiated cells.   
     
     
         13 . The method of  claim 12 , wherein the anti-proliferative cell agent is Ara-C. 
     
     
         14 . The method according to  claim 12 , wherein the mitogen is selected from the group consisting of epidermal growth factor and pokeweed mitogen.