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Short-term grafting of human neural stem cells : Electrophysiological properties and motor behavioral amelioration in experimental Parkinson’s disease

Martínez-Serrano, Alberto; Pereira, Marta P.; Avaliani, Natalia; Nelke, Anna; Kokaia, Merab LU and Ramos-Moreno, Tania LU (2016) In Cell Transplantation 25(12). p.2083-2097
Abstract

Cell replacement therapy in Parkinson’s disease (PD) still lacks a study addressing the acquisition of electrophysiological properties of human grafted neural stem cells and their relation with the emergence of behavioral recovery after transplantation in the short term. Here we study the electrophysiological and biochemical profiles of two ventral mesencephalic human neural stem cell (NSC) clonal lines (C30-Bcl-XL and C32-Bcl-XL) that express high levels of Bcl-XL to enhance their neurogenic capacity, after grafting in an in vitro parkinsonian model. Electrophysiological recordings show that the majority of the cells derived from the transplants are not mature at 6 weeks after grafting, but 6.7% of the... (More)

Cell replacement therapy in Parkinson’s disease (PD) still lacks a study addressing the acquisition of electrophysiological properties of human grafted neural stem cells and their relation with the emergence of behavioral recovery after transplantation in the short term. Here we study the electrophysiological and biochemical profiles of two ventral mesencephalic human neural stem cell (NSC) clonal lines (C30-Bcl-XL and C32-Bcl-XL) that express high levels of Bcl-XL to enhance their neurogenic capacity, after grafting in an in vitro parkinsonian model. Electrophysiological recordings show that the majority of the cells derived from the transplants are not mature at 6 weeks after grafting, but 6.7% of the studied cells showed mature electrophysiological profiles. Nevertheless, parallel in vivo behavioral studies showed a significant motor improvement at 7 weeks postgrafting in the animals receiving C30-Bcl-XL, the cell line producing the highest amount of TH+ cells. Present results show that, at this postgrafting time point, behavioral amelioration highly correlates with the spatial dispersion of the TH+ grafted cells in the caudate putamen. The spatial dispersion, along with a high number of dopaminergic-derived cells, is crucial for behavioral improvements. Our findings have implications for long-term standardization of stem cell-based approaches in Parkinson’s disease.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
A9-dopaminergic phenotype, Electrophysiology, Human neural stem cells (hNSCs), Parkinson’s disease (PD), Ventral mesencephalon
in
Cell Transplantation
volume
25
issue
12
pages
15 pages
publisher
Cognizant Communication Corporation
external identifiers
  • scopus:85007071959
  • wos:000390183200001
ISSN
0963-6897
DOI
10.3727/096368916X692069
language
English
LU publication?
yes
id
c46a774a-bda8-467f-9c5f-b526cd8e2ad1
date added to LUP
2017-01-20 13:10:44
date last changed
2017-11-09 15:09:15
@article{c46a774a-bda8-467f-9c5f-b526cd8e2ad1,
  abstract     = {<p>Cell replacement therapy in Parkinson’s disease (PD) still lacks a study addressing the acquisition of electrophysiological properties of human grafted neural stem cells and their relation with the emergence of behavioral recovery after transplantation in the short term. Here we study the electrophysiological and biochemical profiles of two ventral mesencephalic human neural stem cell (NSC) clonal lines (C30-Bcl-X<sub>L</sub> and C32-Bcl-X<sub>L</sub>) that express high levels of Bcl-X<sub>L</sub> to enhance their neurogenic capacity, after grafting in an in vitro parkinsonian model. Electrophysiological recordings show that the majority of the cells derived from the transplants are not mature at 6 weeks after grafting, but 6.7% of the studied cells showed mature electrophysiological profiles. Nevertheless, parallel in vivo behavioral studies showed a significant motor improvement at 7 weeks postgrafting in the animals receiving C30-Bcl-X<sub>L</sub>, the cell line producing the highest amount of TH<sup>+</sup> cells. Present results show that, at this postgrafting time point, behavioral amelioration highly correlates with the spatial dispersion of the TH<sup>+</sup> grafted cells in the caudate putamen. The spatial dispersion, along with a high number of dopaminergic-derived cells, is crucial for behavioral improvements. Our findings have implications for long-term standardization of stem cell-based approaches in Parkinson’s disease.</p>},
  author       = {Martínez-Serrano, Alberto and Pereira, Marta P. and Avaliani, Natalia and Nelke, Anna and Kokaia, Merab and Ramos-Moreno, Tania},
  issn         = {0963-6897},
  keyword      = {A9-dopaminergic phenotype,Electrophysiology,Human neural stem cells (hNSCs),Parkinson’s disease (PD),Ventral mesencephalon},
  language     = {eng},
  number       = {12},
  pages        = {2083--2097},
  publisher    = {Cognizant Communication Corporation},
  series       = {Cell Transplantation},
  title        = {Short-term grafting of human neural stem cells : Electrophysiological properties and motor behavioral amelioration in experimental Parkinson’s disease},
  url          = {http://dx.doi.org/10.3727/096368916X692069},
  volume       = {25},
  year         = {2016},
}