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Transcriptome analysis reveals transmembrane targets on transplantable midbrain dopamine progenitors.

Bye, Chris R; Jönsson, Marie LU ; Björklund, Anders LU ; Parish, Clare L and Thompson, Lachlan LU (2015) In Proceedings of the National Academy of Sciences 112(15). p.1946-1955
Abstract
An important challenge for the continued development of cell therapy for Parkinson's disease (PD) is the establishment of procedures that better standardize cell preparations for use in transplantation. Although cell sorting has been an anticipated strategy, its application has been limited by lack of knowledge regarding transmembrane proteins that can be used to target and isolate progenitors for midbrain dopamine (mDA) neurons. We used a "FACS-array" approach to identify 18 genes for transmembrane proteins with high expression in mDA progenitors and describe the utility of four of these targets (Alcam, Chl1, Gfra1, and Igsf8) for isolating mDA progenitors from rat primary ventral mesencephalon through flow cytometry. Alcam and Chl1... (More)
An important challenge for the continued development of cell therapy for Parkinson's disease (PD) is the establishment of procedures that better standardize cell preparations for use in transplantation. Although cell sorting has been an anticipated strategy, its application has been limited by lack of knowledge regarding transmembrane proteins that can be used to target and isolate progenitors for midbrain dopamine (mDA) neurons. We used a "FACS-array" approach to identify 18 genes for transmembrane proteins with high expression in mDA progenitors and describe the utility of four of these targets (Alcam, Chl1, Gfra1, and Igsf8) for isolating mDA progenitors from rat primary ventral mesencephalon through flow cytometry. Alcam and Chl1 facilitated a significant enrichment of mDA neurons following transplantation, while targeting of Gfra1 allowed for robust separation of dopamine and serotonin neurons. Importantly, we also show that mDA progenitors isolated on the basis of transmembrane proteins are capable of extensive, functional innervation of the host striatum and correction of motor impairment in a unilateral model of PD. These results are highly relevant for current efforts to establish safe and effective stem cell-based procedures for PD, where clinical translation will almost certainly require safety and standardization measures in order to deliver well-characterized cell preparations. (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
112
issue
15
pages
1946 - 1955
publisher
National Acad Sciences
external identifiers
  • pmid:25775569
  • wos:000352856800019
  • scopus:84928038755
ISSN
1091-6490
DOI
10.1073/pnas.1501989112
language
English
LU publication?
yes
id
94d31b64-d342-498f-88c8-c595a926c004 (old id 5258542)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/25775569?dopt=Abstract
date added to LUP
2015-04-03 20:26:51
date last changed
2017-10-22 03:13:42
@article{94d31b64-d342-498f-88c8-c595a926c004,
  abstract     = {An important challenge for the continued development of cell therapy for Parkinson's disease (PD) is the establishment of procedures that better standardize cell preparations for use in transplantation. Although cell sorting has been an anticipated strategy, its application has been limited by lack of knowledge regarding transmembrane proteins that can be used to target and isolate progenitors for midbrain dopamine (mDA) neurons. We used a "FACS-array" approach to identify 18 genes for transmembrane proteins with high expression in mDA progenitors and describe the utility of four of these targets (Alcam, Chl1, Gfra1, and Igsf8) for isolating mDA progenitors from rat primary ventral mesencephalon through flow cytometry. Alcam and Chl1 facilitated a significant enrichment of mDA neurons following transplantation, while targeting of Gfra1 allowed for robust separation of dopamine and serotonin neurons. Importantly, we also show that mDA progenitors isolated on the basis of transmembrane proteins are capable of extensive, functional innervation of the host striatum and correction of motor impairment in a unilateral model of PD. These results are highly relevant for current efforts to establish safe and effective stem cell-based procedures for PD, where clinical translation will almost certainly require safety and standardization measures in order to deliver well-characterized cell preparations.},
  author       = {Bye, Chris R and Jönsson, Marie and Björklund, Anders and Parish, Clare L and Thompson, Lachlan},
  issn         = {1091-6490},
  language     = {eng},
  number       = {15},
  pages        = {1946--1955},
  publisher    = {National Acad Sciences},
  series       = {Proceedings of the National Academy of Sciences},
  title        = {Transcriptome analysis reveals transmembrane targets on transplantable midbrain dopamine progenitors.},
  url          = {http://dx.doi.org/10.1073/pnas.1501989112},
  volume       = {112},
  year         = {2015},
}