Sl. Minger et al., LONG-TERM SURVIVAL OF TRANSPLANTED BASAL FOREBRAIN CELLS FOLLOWING IN-VITRO PROPAGATION WITH FIBROBLAST GROWTH FACTOR-II, Experimental neurology, 141(1), 1996, pp. 12-24
The intracerebral transplantation of freshly dissected fetal tissue co
ntaining cholinergic neurons of the developing basal forebrain has bee
n reported to reverse lesion-induced or age-related cognitive deficits
in animal models of cholinergic neuronal degeneration. Grafts of cult
ured fetal neurons, however, have generally shown poor cellular surviv
al and limited therapeutic benefit. We tested the hypothesis that rece
nt advances in the identification of growth factors that promote the s
urvival and propagation of fetal precursor cells in vitro would improv
e the long-term survival of cultured neurons following intracerebral i
mplantation. Dissociated cells from gestational Day 14 rodent basal fo
rebrain were grown in chemically defined media supplemented with 28 ng
/ml basic fibroblast growth factor. Two weeks postplating, numerous ce
lls were present in the cultures and showed iunmunoreactive labeling f
or a variety of markers, including glutamic acid decarboxylase, neuron
-specific enolase, neurofilament proteins, glial fibrillary acidic pro
tein. and, occasionally, choline. acetyltransferase. To determine if c
ultured basal forebrain cells would survive intracerebral implantation
, the cells were implanted homotypically into the nucleus basalis magn
ocellularis. To enhance the potential for graft survival in vivo, cell
s were also implanted into the nucleus basalis magnocellularis followi
ng an ibotenic acid lesion and into the denervated frontal cortex. Ani
mals sacrificed between 2 weeks and 7 months following transplantation
showed good and comparable graft survival in all sites. Immunocytoche
mical analysis revealed that representative populations of cells obser
ved in vitro survived for prolonged periods in vivo even in sites dist
al from their normal cellular targets. Thus, neuronal populations expa
nded in vitro can successfully survive and maintain cellular phenotype
s post-transplantation. These results suggest a potential for isolatin
g and growing specific neuronal populations in vitro for intracerebral
transplantation. (C) 1996 Academic Press, Inc.