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Identification of growth factors that promote long‐term proliferation of olfactory ensheathing cells and modulate their antigenic phenotype
Author(s) -
Alexander Claire L.,
Fitzgerald Una F.,
Barnett Susan C.
Publication year - 2002
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.10044
Subject(s) - olfactory ensheathing glia , astrocyte , biology , microbiology and biotechnology , schwann cell , neuroglia , basic fibroblast growth factor , olfactory bulb , growth factor , olfactory system , nerve growth factor , olfactory marker protein , olfactory receptor , neuroscience , immunology , receptor , central nervous system , biochemistry
Olfactory ensheathing cells can develop into distinct subtypes in culture after incubation in serum‐free medium conditioned by astrocytes, which have Schwann cell–like and astrocyte‐like properties. It has not been possible so far to modulate and grow large numbers of these olfactory ensheathing cell subtypes. In this study, we have shown that astrocyte‐conditioned medium, although promoting differentiation of the two olfactory ensheathing cell types, is growth‐restrictive after 14 days, probably due to the upregulation of p16 and p27. Growth arrest can be overridden and cells maintained for a further 11 weeks, by a mitogen mix of fibroblast growth factor 2, forskolin, and heregulin (olfactory mitogen medium) combined with astrocyte‐conditioned medium. In the absence of astrocyte‐conditioned medium, combinations of the same factors can also override growth arrest but to a lesser extent. Olfactory mitogen medium combined with astrocyte‐conditioned medium upregulates O4 and low‐affinity nerve growth factor receptor expression on olfactory ensheathing cells, leading to a 100% Schwann cell–like phenotype. If cells are maintained in olfactory mitogen medium alone, or if they are treated with forskolin or fibroblast growth factor 2 diluted in serum‐free medium, O4 and low‐affinity nerve growth factor receptor expression remains at 100%, but there is also an increase in expression of E‐NCAM, the astrocyte‐like marker. Medium containing serum also overrides growth arrest, but for only 4 weeks, during which time most differentiation‐specific markers disappear. These studies have allowed us to define conditions to modulate the olfactory ensheathing cell phenotype. GLIA 37:349–364, 2002. © 2002 Wiley‐Liss, Inc.