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Migration patterns and phenotypic differentiation of long-term expanded human neural progenitor cells after transplantation into the adult rat brain.

Englund Johansson, Ulrica LU ; Björklund, Anders LU and Wictorin, Klas LU (2002) In Developmental Brain Research 134(1-2). p.123-141
Abstract
We have examined long-term growth-factor expanded human neural progenitors following transplantation into the adult rat brain. Cells, obtained from the forebrain of a 9-week old fetus, propagated in the presence of epidermal growth factor, basic fibroblast growth factor, and leukemia inhibitory factor were transplanted into the striatum, subventricular zone (SVZ), and hippocampus. At 14 weeks, implanted cells were identified using antisera recognizing human nuclei and the reporter gene green fluorescent protein. Different migration patterns of the grafted cells were observed: (i) target-directed migration of doublecortin (DCX, a marker for migrating neuroblasts)-positive cells along the rostral migratory stream to the olfactory bulb and... (More)
We have examined long-term growth-factor expanded human neural progenitors following transplantation into the adult rat brain. Cells, obtained from the forebrain of a 9-week old fetus, propagated in the presence of epidermal growth factor, basic fibroblast growth factor, and leukemia inhibitory factor were transplanted into the striatum, subventricular zone (SVZ), and hippocampus. At 14 weeks, implanted cells were identified using antisera recognizing human nuclei and the reporter gene green fluorescent protein. Different migration patterns of the grafted cells were observed: (i) target-directed migration of doublecortin (DCX, a marker for migrating neuroblasts)-positive cells along the rostral migratory stream to the olfactory bulb and into the granular cell layer following transplantation into the SVZ and hippocampus, respectively; (ii) non-directed migration of DCX-positive cells in the grey matter in striatum and hippocampus, and (iii) extensive migration of above all nestin-positive/DCX-negative cells within white matter tracts. At the striatal implantation site, neuronal differentiation was most pronounced at the graft core with axonal projections extending along the internal capsule bundles. In the hippocampus, cells differentiated primarily into interneurons both in the dentate gyrus and in the CA1-3 regions as well as into granule-like neurons. In the striatum and hippocampus, a significant proportion of the grafted cells differentiated into glial cells, some with long processes extending along white matter tracts. Although the survival time was over 3 months in the present study a large fraction of the grafted cells remained undifferentiated in a stem or progenitor cell stage as revealed by the expression of nestin and/or GFAP. (Less)
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keywords
Stem Cells : physiology, Stem Cells : pathology, Sprague-Dawley, Rats, Phenotype, Neurons : pathology, Human, Hippocampus : surgery, Hippocampus : pathology, Graft Survival, Female, Corpus Striatum : surgery, Corpus Striatum : pathology, Cell Line, Cell Movement, Stem Cells : transplantation, Support, Non-U.S. Gov't, Time Factors, Cell Differentiation, Brain : surgery, Animal
in
Developmental Brain Research
volume
134
issue
1-2
pages
123 - 141
publisher
Elsevier
external identifiers
  • wos:000175354200013
  • pmid:11947943
  • scopus:0037204595
ISSN
0165-3806
DOI
10.1016/S0165-3806(01)00330-3
language
English
LU publication?
yes
id
ff498e8f-447d-4946-b59f-6270eac26a90 (old id 107542)
alternative location
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11947943&dopt=Abstract
date added to LUP
2007-07-11 16:20:23
date last changed
2017-09-24 04:17:41
@article{ff498e8f-447d-4946-b59f-6270eac26a90,
  abstract     = {We have examined long-term growth-factor expanded human neural progenitors following transplantation into the adult rat brain. Cells, obtained from the forebrain of a 9-week old fetus, propagated in the presence of epidermal growth factor, basic fibroblast growth factor, and leukemia inhibitory factor were transplanted into the striatum, subventricular zone (SVZ), and hippocampus. At 14 weeks, implanted cells were identified using antisera recognizing human nuclei and the reporter gene green fluorescent protein. Different migration patterns of the grafted cells were observed: (i) target-directed migration of doublecortin (DCX, a marker for migrating neuroblasts)-positive cells along the rostral migratory stream to the olfactory bulb and into the granular cell layer following transplantation into the SVZ and hippocampus, respectively; (ii) non-directed migration of DCX-positive cells in the grey matter in striatum and hippocampus, and (iii) extensive migration of above all nestin-positive/DCX-negative cells within white matter tracts. At the striatal implantation site, neuronal differentiation was most pronounced at the graft core with axonal projections extending along the internal capsule bundles. In the hippocampus, cells differentiated primarily into interneurons both in the dentate gyrus and in the CA1-3 regions as well as into granule-like neurons. In the striatum and hippocampus, a significant proportion of the grafted cells differentiated into glial cells, some with long processes extending along white matter tracts. Although the survival time was over 3 months in the present study a large fraction of the grafted cells remained undifferentiated in a stem or progenitor cell stage as revealed by the expression of nestin and/or GFAP.},
  author       = {Englund Johansson, Ulrica and Björklund, Anders and Wictorin, Klas},
  issn         = {0165-3806},
  keyword      = {Stem Cells : physiology,Stem Cells : pathology,Sprague-Dawley,Rats,Phenotype,Neurons : pathology,Human,Hippocampus : surgery,Hippocampus : pathology,Graft Survival,Female,Corpus Striatum : surgery,Corpus Striatum : pathology,Cell Line,Cell Movement,Stem Cells : transplantation,Support,Non-U.S. Gov't,Time Factors,Cell Differentiation,Brain : surgery,Animal},
  language     = {eng},
  number       = {1-2},
  pages        = {123--141},
  publisher    = {Elsevier},
  series       = {Developmental Brain Research},
  title        = {Migration patterns and phenotypic differentiation of long-term expanded human neural progenitor cells after transplantation into the adult rat brain.},
  url          = {http://dx.doi.org/10.1016/S0165-3806(01)00330-3},
  volume       = {134},
  year         = {2002},
}