Platelet derived growth factor (pdgf)-derived neurospheres define a novel class of progenitor cells

Abstract

The present invention is related to the discovery of a novel class of neural progenitor cells, which proliferate in response to platelet derived growth factor (PDGF) and differentiate into neurons and oligodendrocytes but not astrocytes. Progeny of the progenitor cells can be obtained by culturing brain tissue in PDGF without serum, epidermal growth factor (EGF), fibroblast growth factor 2, or transforming growth factor alpha. Upon subculturing into EGF-containing media, these progeny cells can proliferate and form neurospheres, whereas PDGF has no such effect.

1 - 18 . (canceled) 
     
     
         19 . A method of inducing proliferation of a neural progenitor cell in mammal, the method comprising administering an effective amount of a platelet derived growth factor (PDGF) to the mammal. 
     
     
         20 . The method of  claim 19 , wherein the mammal has a neurodegenerative condition or disease. 
     
     
         21 . The method of  claim 20 , wherein the neurodegenerative condition or disease is Parkinson's disease. 
     
     
         22 . The method of  claim 19 , wherein the PDGF is administered into the brain of the mammal. 
     
     
         23 . The method of  claim 19 , further comprising administering one or more additional growth factors or biological agents. 
     
     
         24 . The method of  claim 23 , wherein the one or more additional growth factors or biological agents are selected from the group consisting of BGF, PDGF, FGF-1, FGF-2, TGF-α, TGF-β, nerve growth factor (NGF), ciliary neurotrophic factor (CNTF), brain derived neurotrophic factor (BDNF), neurotrophin 3, neurotrophin 4, leukemia inhibitory factor (LIF), bone morphogenic protein 2 (BMP-2), insulin-like growth factor, insulin, growth factor, prolactin, interleukin, forskolin, cAMP and cAMP analog, pituitary adenylate cyclase activating polypeptide (PACAP), phorbal ester, estrogen, and ovarian hormone. 
     
     
         25 . A method of treating or ameliorating a neurodegenerative condition or disease in a mammal, the method comprising administering an effective amount of a platelet derived growth factor (PDGF) to the mammal. 
     
     
         26 . The method of  claim 25 , wherein the neurodegenerative condition or disease is Parkinson's disease. 
     
     
         27 . The method of  claim 25 , wherein the PDGF is administered into the brain of the mammal. 
     
     
         28 . The method of  claim 25 , further comprising administering one or more additional growth factors or biological agents. 
     
     
         29 . The method of  claim 28 , wherein the one or more additional growth factors or biological agents are selected from the group consisting of BGF, PDGF, FGF-1, FGF-2, TGF-α, TGF-β, nerve growth factor (NGF), ciliary neurotrophic factor (CNTF), brain derived neurotrophic factor (BDNF), neurotrophin 3, neurotrophin 4, leukemia inhibitory factor (LIF), bone morphogenic protein 2 (BMP-2), insulin-like growth factor, insulin, growth factor, prolactin, interleukin, forskolin, cAMP and cAMP analog, pituitary adenylate cyclase activating polypeptide (PACAP), phorbal ester, estrogen, and ovarian hormone. 
     
     
         30 . A pharmaceutical composition comprising platelet derived growth factor (PDGF) for administration to a mammal for treating or ameliorating a neurodegenerative condition or disease. 
     
     
         31 . The pharmaceutical composition of  claim 30 , wherein the neurodegenerative condition or disease is Parkinson's disease. 
     
     
         32 . The pharmaceutical composition of  claim 30 , wherein the pharmaceutical composition is for administration to the brain of the mammal.