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Integration and function of new neurons generated from fibroblasts and adult neural stem cells in the pathological brain

Wood, James LU (2011) In Lund University, Faculty of Medicine Doctoral Dissertation Series 2011:112.
Abstract
In Papers One through Six we have investigated the function and integration of “new” neurons – new neurons born from neural stem cells in the adult brain, and new neurons in the sense that they were generated from fibroblasts.

Papers One and Two focused on the new neurons generated from neural stem cells in the SVZ and SGZ after pathological insults. We investigated how the newly generated neurons migrate and integrate in the brain. These two phenomena, migration and integration are intimately linked. Without the proper migratory cues new cells exhibit ectopic placement and aberrant integration, as observed in the hippocampus after severe epileptic insults.

Papers Three to Six focused on generating (and characterizing)... (More)
In Papers One through Six we have investigated the function and integration of “new” neurons – new neurons born from neural stem cells in the adult brain, and new neurons in the sense that they were generated from fibroblasts.

Papers One and Two focused on the new neurons generated from neural stem cells in the SVZ and SGZ after pathological insults. We investigated how the newly generated neurons migrate and integrate in the brain. These two phenomena, migration and integration are intimately linked. Without the proper migratory cues new cells exhibit ectopic placement and aberrant integration, as observed in the hippocampus after severe epileptic insults.

Papers Three to Six focused on generating (and characterizing) neurons from fibroblasts. First it was crucial to investigate the functional characteristics of the newly generated neurons to demonstrate that they indeed had the properties of mature neurons. The functional properties of the new cells will determine how and importantly if they will integrate in the brain. This is of key importance if we envision using iN or iPS cells for transplantation in the future. In Paper 6 we demonstrate for the first time that transplanted iPS cells survive, migrate beyond the transplantation core, and exhibit the functional properties of mature neurons.

Taken together, this thesis demonstrates that the environment encountered by new neurons will influence their migration and integration. We also demonstrate that human fibroblasts can be reprogrammed to neurons and show that fibroblast-derived neurons can integrate in the mammalian brain. Thus, fibroblasts may be a valuable source of neurons for transplantation but the environment encountered will influence their integration and function which will determine their therapeutic effect. (Less)
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author
supervisor
opponent
  • PhD Jessberger, Sebastian, Institute of Cell Biology, Swiss Federal Institute for Technology, Zurich
organization
publishing date
type
Thesis
publication status
published
subject
keywords
neurogenesis, neural stem cells, iNs, iPS cells, stroke, epilepsy, electrophysiology
in
Lund University, Faculty of Medicine Doctoral Dissertation Series
volume
2011:112
pages
152 pages
publisher
Laboratory of Neurogenesis and Cell Therapy
defense location
Segerfalksalen, Wallenberg Neuroscience Center
defense date
2011-12-20 09:00
ISSN
1652-8220
ISBN
978-91-86871-62-8
language
English
LU publication?
yes
id
009ab1d0-cd6c-4bdb-9de7-b52245bf0411 (old id 2206020)
date added to LUP
2011-11-23 09:12:58
date last changed
2016-09-19 08:44:47
@phdthesis{009ab1d0-cd6c-4bdb-9de7-b52245bf0411,
  abstract     = {In Papers One through Six we have investigated the function and integration of “new” neurons – new neurons born from neural stem cells in the adult brain, and new neurons in the sense that they were generated from fibroblasts. <br/><br>
	Papers One and Two focused on the new neurons generated from neural stem cells in the SVZ and SGZ after pathological insults. We investigated how the newly generated neurons migrate and integrate in the brain. These two phenomena, migration and integration are intimately linked. Without the proper migratory cues new cells exhibit ectopic placement and aberrant integration, as observed in the hippocampus after severe epileptic insults.<br/><br>
	Papers Three to Six focused on generating (and characterizing) neurons from fibroblasts. First it was crucial to investigate the functional characteristics of the newly generated neurons to demonstrate that they indeed had the properties of mature neurons. The functional properties of the new cells will determine how and importantly if they will integrate in the brain. This is of key importance if we envision using iN or iPS cells for transplantation in the future. In Paper 6 we demonstrate for the first time that transplanted iPS cells survive, migrate beyond the transplantation core, and exhibit the functional properties of mature neurons.<br/><br>
	Taken together, this thesis demonstrates that the environment encountered by new neurons will influence their migration and integration. We also demonstrate that human fibroblasts can be reprogrammed to neurons and show that fibroblast-derived neurons can integrate in the mammalian brain. Thus, fibroblasts may be a valuable source of neurons for transplantation but the environment encountered will influence their integration and function which will determine their therapeutic effect.},
  author       = {Wood, James},
  isbn         = {978-91-86871-62-8},
  issn         = {1652-8220},
  keyword      = {neurogenesis,neural stem cells,iNs,iPS cells,stroke,epilepsy,electrophysiology},
  language     = {eng},
  pages        = {152},
  publisher    = {Laboratory of Neurogenesis and Cell Therapy},
  school       = {Lund University},
  series       = {Lund University, Faculty of Medicine Doctoral Dissertation Series},
  title        = {Integration and function of new neurons generated from fibroblasts and adult neural stem cells in the pathological brain},
  volume       = {2011:112},
  year         = {2011},
}