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Grafted neural stem cells develop into functional pyramidal neurons and integrate into host cortical circuitry.

Englund, Ulrica; Björklund, Anders LU ; Wictorin, Klas LU ; Lindvall, Olle LU and Kokaia, Merab LU (2002) In Proceedings of the National Academy of Sciences 99(26). p.17089-17094
Abstract
In vitro expanded neural stem/progenitor cells can undergo region-specific differentiation after transplantation to the developing or adult brain, and display morphologies and markers characteristic of mature neurons. Here we have used patch-clamp techniques to explore whether grafted stem cells also can develop physiological properties of mature neurons and become functionally integrated within host neural circuitry. The immortalized neural progenitor cell line, RN33B, prelabeled with GFP by using a lentiviral vector, was transplanted into the cortex or hippocampus of neonatal rats. We found that the grafted GFP-positive cells differentiated into cells with morphological features of cortical or hippocampal pyramidal neurons, and that many... (More)
In vitro expanded neural stem/progenitor cells can undergo region-specific differentiation after transplantation to the developing or adult brain, and display morphologies and markers characteristic of mature neurons. Here we have used patch-clamp techniques to explore whether grafted stem cells also can develop physiological properties of mature neurons and become functionally integrated within host neural circuitry. The immortalized neural progenitor cell line, RN33B, prelabeled with GFP by using a lentiviral vector, was transplanted into the cortex or hippocampus of neonatal rats. We found that the grafted GFP-positive cells differentiated into cells with morphological features of cortical or hippocampal pyramidal neurons, and that many of them had established appropriate cortico-thalamic and contralateral hippocampal connections, respectively, as revealed by retrograde tracing. Whole-cell patch-clamp recordings from grafted cells with morphological characteristics of pyramidal neurons showed that they were able to generate action potentials, and received functional excitatory and inhibitory synaptic inputs from neighboring cells. These data provide evidence that grafted neural progenitors can differentiate into morphologically mature pyramidal projection neurons, establish appropriate long-distance axonal projections, exhibit normal electrophysiological properties, and become functionally integrated into host cortical circuitry. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Proceedings of the National Academy of Sciences
volume
99
issue
26
pages
17089 - 17094
publisher
National Acad Sciences
external identifiers
  • wos:000180101600104
  • scopus:0037168599
ISSN
1091-6490
DOI
10.1073/pnas.252589099
language
English
LU publication?
yes
id
8e6fd87e-8f62-4302-9a74-f3522dab4287 (old id 111530)
date added to LUP
2007-06-26 09:49:48
date last changed
2017-10-22 03:50:13
@article{8e6fd87e-8f62-4302-9a74-f3522dab4287,
  abstract     = {In vitro expanded neural stem/progenitor cells can undergo region-specific differentiation after transplantation to the developing or adult brain, and display morphologies and markers characteristic of mature neurons. Here we have used patch-clamp techniques to explore whether grafted stem cells also can develop physiological properties of mature neurons and become functionally integrated within host neural circuitry. The immortalized neural progenitor cell line, RN33B, prelabeled with GFP by using a lentiviral vector, was transplanted into the cortex or hippocampus of neonatal rats. We found that the grafted GFP-positive cells differentiated into cells with morphological features of cortical or hippocampal pyramidal neurons, and that many of them had established appropriate cortico-thalamic and contralateral hippocampal connections, respectively, as revealed by retrograde tracing. Whole-cell patch-clamp recordings from grafted cells with morphological characteristics of pyramidal neurons showed that they were able to generate action potentials, and received functional excitatory and inhibitory synaptic inputs from neighboring cells. These data provide evidence that grafted neural progenitors can differentiate into morphologically mature pyramidal projection neurons, establish appropriate long-distance axonal projections, exhibit normal electrophysiological properties, and become functionally integrated into host cortical circuitry.},
  author       = {Englund, Ulrica and Björklund, Anders and Wictorin, Klas and Lindvall, Olle and Kokaia, Merab},
  issn         = {1091-6490},
  language     = {eng},
  number       = {26},
  pages        = {17089--17094},
  publisher    = {National Acad Sciences},
  series       = {Proceedings of the National Academy of Sciences},
  title        = {Grafted neural stem cells develop into functional pyramidal neurons and integrate into host cortical circuitry.},
  url          = {http://dx.doi.org/10.1073/pnas.252589099},
  volume       = {99},
  year         = {2002},
}