Lineage Restricted Glial Precursors from the Central Nervous System

Abstract

A glial precursor cell population from mammalian central nervous system has been isolated. These A2B5 + E-NCAM − glial-restricted precursor (GRP) cells are capable of differentiating into oligodendrocytes, A2B5 + process-bearing astrocytes, and A2B5 − fibroblast-like astrocytes, but not into neurons. GRP cells can be maintained by regeneration in culture. GRP cells differ from oligodendrocyte-type-2 astrocyte (O-2A) progenitor cells in growth factor requirements, morphology, and progeny. Methods of use of GRP cells are also disclosed.

1 . A method for screening for potentially neurologically therapeutic compounds comprising exposing mammalian glial restricted precursor cells or derivatives thereof or mixtures thereof cultured in vitro to the compound and monitoring a response of said cells. 
     
     
         2 . The method of  claim 1  wherein said mammalian glial restricted precursor cells are human cells. 
     
     
         3 . The method of  claim 1  wherein said mammalian glial restricted precursor cells are exposed to a compound at varying dosages. 
     
     
         4 . The method of  claim 1  wherein said mammalian glial restricted precursor cells are exposed to a compound for various time periods. 
     
     
         5 . The method of  claim 1  wherein said mammalian glial restricted precursor cells are exposed to a compound at varying dosages for various time periods. 
     
     
         6 . The method of  claim 1  wherein the monitored response of said cells is a change in level of expression of an enzyme, receptor, cell surface molecule, neurotransmitter, amino acid, neuropeptide, or biogenic amine upon exposure to the compound. 
     
     
         7 . The method of  claim 6  wherein the change in level of expression is an increase. 
     
     
         8 . The method of  claim 6  wherein the change in level of expression is a decrease. 
     
     
         9 . The method of  claim 1  wherein the monitored response of said cells is promoting division of said cells measured by an increase in cell number. 
     
     
         10 . The method of  claim 1  wherein the monitored response of said cells is promoting DNA synthesis in said cells. 
     
     
         11 . The method of  claim 1  further comprising applying an agent to said cells in conditions where said cells are expected to die and monitoring cell survival in the presence of the compound. 
     
     
         12 . A method for screening for a compound that inhibits binding to a selected receptor on a glial restricted precursor cell, said method comprising contacting glial restricted precursors with a compound and determining the ability of the compound to block a response elicited by binding of an agonist to the selected receptor on the glial restricted precursor cells. 
     
     
         13 . A method for screening for compounds which activate a selected receptor on a glial restricted precursor cell, said method comprising contacting glial restricted precursors with a compound and measuring a physiological alteration in said cells associated with activation of said receptor.