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Adrenal Chromaffin Cells Transdifferentiate in Response to Basic Fibroblast Growth Factor and Show Directed Outgrowth to a Nerve Growth Factor Source in Vivo

Chalmers, Gordon R. and Fisher, Lisa J. and Niijima, Kenji and Patterson, Paul H. and Gage, Fred H. (1995) Adrenal Chromaffin Cells Transdifferentiate in Response to Basic Fibroblast Growth Factor and Show Directed Outgrowth to a Nerve Growth Factor Source in Vivo. Experimental Neurology, 133 (1). pp. 32-42. ISSN 0014-4886. doi:10.1006/exnr.1995.1005. https://resolver.caltech.edu/CaltechAUTHORS:20160323-083517049

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Abstract

Chromaffin cells exposed to basic fibroblast growth factor (bFGF) in vitro express characteristics of sympathetic neurons, extend neurites, and become dependent on nerve growth factor (NGF) for survival. We explored whether the growth factor responsiveness of chromaffin cells could be exploited to enhance the transdifferentiation, neurite outgrowth and functional efficacy of chromaffin cells implanted into rats with unilateral 6-hydroxydopamine lesions. Cografts of neonatal chromaffin cells and fibroblasts genetically modified to produce bFGF were placed into the dopamine-depleted striatum of adult rats. Either control-transfected or NGF-producing fibroblasts were then transplanted 1 mm distal to the cograft. Chromaffin cells transdifferentiated under the influence of bFGF, as indicated by the growth of neurites and the expression of neuron-specific proteins. Distal grafts of NGF-producing fibroblasts successfully induced chromaffin neurites to traverse through the host parenchyma to the NGF source. In the absence of NGF fibroblast grafts, neither neurite extension nor good, long-term survival of the chromaffin-derived neurons was observed. Assessments of apomorphine-induced rotational behavior 2- and 4-weeks postgrafting revealed no behavioral improvements in any of the groups. These results indicate that localized sources of growth factors are effective in inducing the transdifferentiation of grafted chromaffin cells as well as the extension of chromaffin-derived neurites into the host parenchyma. Such chromaffin cell-derived neurons are, however, functionally ineffective in this rat model of Parkinson's disease. Whether the lack of behavioral improvement reflected the tropic growth of neurites to an inappropriate striatal region or the noradrenergic nature of the chromaffin cell-derived neurons remains to be clarified. Nonetheless, these results caution that promoting transdifferentiation and neurite extension from engrafted chromaffin cells may not be sufficient to achieve desired functional effects of such grafts.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1006/exnr.1995.1005DOIArticle
http://www.sciencedirect.com/science/article/pii/S0014488685710059PublisherArticle
Additional Information:© 1995 Academic Press. Available online 29 April 2002. This work was supported by NIH (AG10435, AG08514), The Parkinson's Disease Foundation, The Margaret and Herbert Hoover Foundation, Allied Signal Award and Metropolitan Life Award to F.H.G., and Amgen Inc. to P.H.P. K.N. was supported by a CNS fellowship from Eli Lilly Japan K.K.
Funders:
Funding AgencyGrant Number
NIHAG10435
NIHAG08514
Parkinson's Disease FoundationUNSPECIFIED
Margaret and Herbert Hoover FoundationUNSPECIFIED
Allied Signal AwardUNSPECIFIED
Metropolitan Life AwardUNSPECIFIED
Amgen Inc.UNSPECIFIED
CNS fellowshipUNSPECIFIED
Issue or Number:1
DOI:10.1006/exnr.1995.1005
Record Number:CaltechAUTHORS:20160323-083517049
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20160323-083517049
Official Citation:Gordon R. Chalmers, Lisa J. Fisher, Kenji Niijima, Paul H. Patterson, Fred H. Gage, Adrenal Chromaffin Cells Transdifferentiate in Response to Basic Fibroblast Growth Factor and Show Directed Outgrowth to a Nerve Growth Factor Source in Vivo, Experimental Neurology, Volume 133, Issue 1, May 1995, Pages 32-42, ISSN 0014-4886, http://dx.doi.org/10.1006/exnr.1995.1005. (http://www.sciencedirect.com/science/article/pii/S0014488685710059)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:65607
Collection:CaltechAUTHORS
Deposited By: Ruth Sustaita
Deposited On:24 Mar 2016 17:47
Last Modified:10 Nov 2021 23:47

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