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Enhanced Survival and Neuronal Differentiation of Adrenal Chromaffin Cells Cografted into the Striatum with NGF-producing Fibroblasts

Niijima, Kenji and Chalmers, Gordon R. and Peterson, Daniel A. and Fisher, Lisa J. and Patterson, Paul H. and Gage, Fred H. (1995) Enhanced Survival and Neuronal Differentiation of Adrenal Chromaffin Cells Cografted into the Striatum with NGF-producing Fibroblasts. Journal of Neuroscience, 15 (2). pp. 1180-1194. ISSN 0270-6474. PMCID PMC6577834. doi:10.1523/JNEUROSCI.15-02-01180.1995.

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Although adrenal medullary chromaffin cells have been used extensively for intracerebral grafting, their survival has generally been poor. Improved survival of the implanted cells has been achieved by exposing the chromaffin cells to NGF in vivo. Culture studies have shown, however, that chromaffin cells are converted into sympathetic neurons when NGF is included in the medium. The degree to which such a transdifferentiation may occur in vivo has not been determined. We assessed the effects of cografting chromaffin cells with primary fibroblasts genetically engineered to express NGF. Chromaffin cells from 10 d old rats were implanted with NGF-producing or beta- galactosidase-producing primary fibroblasts (control fibroblasts) into the striatum of 6-hydroxydopamine treated adult rats of the same strain. Eight weeks postgrafting, chromaffin cells cografted with NGF- producing fibroblasts displayed many of the features of mature sympathetic neurons such as large somata, long processes, transmitter vesicles similar to those found in neurons, and positive immunolabeling for the neuronal markers neurofilament, MAP2 and SCG10. Chromaffin- derived neuron number was also significantly enhanced in the presence of NGF-producing fibroblasts. While control fibroblasts were also found to increase chromaffin cell number above that of chromaffin cells grafted alone, the control fibroblasts did not induce neuronal transdifferentiation. These results demonstrate that chromaffin cells cografted with NGF-producing fibroblasts undergo transdifferentiation in vivo and express many characteristics of mature sympathetic neurons. The consequences of this transdifferentiation on the long term survival and function of the transplanted cells in vivo remain to be clarified.

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Additional Information:© 1995 by Society for Neuroscience. Beginning six months after publication the Work will be made freely available to the public on SfN’s website to copy, distribute, or display under a Creative Commons Attribution 4.0 International (CC BY 4.0) license ( Received Mar 21; revised July 25, 1994; accepted Aug 2, 1994. K.N. and G.R.C. contributed equally to this article. This work was supported by NIH AG 10435 and AG 08514, 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 of Eli Lilly Japan K.K. D.A.P. was supported by NIH Fellowship AGO 5512-02. We thank Dr. David J. Anderson for the anti-SCG 10 antibody, Dr. Ikuko Nagatsu forthe anti-TH antibody, Mr. Ming-Ji Fann for contributions to the early stages of this work, and Ms. Doreen McDowell for media preparation.
Funding AgencyGrant Number
NIHAG 10435
NIHAG 08514
Margaret and Herbert Hoover FoundationUNSPECIFIED
Metropolitan LifeUNSPECIFIED
NIHAGO 5512-02
Subject Keywords:adrenal chromaffin cells, autograft, NGF, transdifferentiation, genetically engineered fibroblasts
Issue or Number:2
PubMed Central ID:PMC6577834
Record Number:CaltechAUTHORS:20160401-111603520
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Official Citation:Enhanced survival and neuronal differentiation of adrenal chromaffin cells cografted into the striatum with NGF-producing fibroblasts. K Niijima, GR Chalmers, DA Peterson, LJ Fisher, PH Patterson, FH Gage. Journal of Neuroscience 1 February 1995, 15 (2) 1180-1194; DOI: 10.1523/JNEUROSCI.15-02-01180.1995
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:65851
Deposited By: Ruth Sustaita
Deposited On:01 Apr 2016 19:56
Last Modified:17 Feb 2022 00:27

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