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Evaluation of TH-Cre knock-in cell lines for detection and specific targeting of stem cell-derived dopaminergic neurons

Fiorenzano, Alessandro LU ; Birtele, Marcella LU orcid ; Wahlestedt, Jenny Nelander LU orcid and Parmar, Malin LU orcid (2021) In Heliyon 7(1).
Abstract
The focal and progressive degeneration of dopaminergic (DA) neurons in ventral midbrain has made Parkinson's disease (PD) a particularly interesting target of cell-based therapies. However, ethical issues and limited tissue availability have so far hindered the widespread use of human fetal tissue in cell-replacement therapy. DA neurons derived from human pluripotent stem cells (hPSCs) offer unprecedented opportunities to access a renewable source of cells suitable for PD therapeutic applications. To better understand the development and functional properties of stem-cell derived DA neurons, we generated targeted hPSC lines with the gene coding for Cre recombinase knocked into the TH locus. When combined with flexed GFP, they... (More)
The focal and progressive degeneration of dopaminergic (DA) neurons in ventral midbrain has made Parkinson's disease (PD) a particularly interesting target of cell-based therapies. However, ethical issues and limited tissue availability have so far hindered the widespread use of human fetal tissue in cell-replacement therapy. DA neurons derived from human pluripotent stem cells (hPSCs) offer unprecedented opportunities to access a renewable source of cells suitable for PD therapeutic applications. To better understand the development and functional properties of stem-cell derived DA neurons, we generated targeted hPSC lines with the gene coding for Cre recombinase knocked into the TH locus. When combined with flexed GFP, they serve as reporter cell lines able to identify and isolate TH+ neurons in vitro and after transplantation in vivo. These TH-Cre lines provide a valuable genetic tool to manipulate DA neurons useful for the design of more precise DA differentiation protocols and the study of these cells after transplantation in pre-clinical animal models of PD. (Less)
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author
; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Cell transplantation, Dopamine differentiation, Human pluripotent stem cells, Parkinson's disease
in
Heliyon
volume
7
issue
1
article number
e06006
publisher
Elsevier
external identifiers
  • scopus:85100186345
  • pmid:33532642
ISSN
2405-8440
DOI
10.1016/j.heliyon.2021.e06006
language
English
LU publication?
yes
id
fe64e2bb-968f-4ed0-a244-022fdbc1fe03
date added to LUP
2021-02-11 13:50:30
date last changed
2024-07-11 08:38:03
@article{fe64e2bb-968f-4ed0-a244-022fdbc1fe03,
  abstract     = {{The focal and progressive degeneration of dopaminergic (DA) neurons in ventral midbrain has made Parkinson's disease (PD) a particularly interesting target of cell-based therapies. However, ethical issues and limited tissue availability have so far hindered the widespread use of human fetal tissue in cell-replacement therapy. DA neurons derived from human pluripotent stem cells (hPSCs) offer unprecedented opportunities to access a renewable source of cells suitable for PD therapeutic applications. To better understand the development and functional properties of stem-cell derived DA neurons, we generated targeted hPSC lines with the gene coding for Cre recombinase knocked into the <em>TH</em> locus. When combined with flexed GFP, they serve as reporter cell lines able to identify and isolate TH<sup>+</sup> neurons <em>in vitro</em> and after transplantation <em>in vivo</em>. These <em>TH</em>-Cre lines provide a valuable genetic tool to manipulate DA neurons useful for the design of more precise DA differentiation protocols and the study of these cells after transplantation in pre-clinical animal models of PD.}},
  author       = {{Fiorenzano, Alessandro and Birtele, Marcella and Wahlestedt, Jenny Nelander and Parmar, Malin}},
  issn         = {{2405-8440}},
  keywords     = {{Cell transplantation; Dopamine differentiation; Human pluripotent stem cells; Parkinson's disease}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Elsevier}},
  series       = {{Heliyon}},
  title        = {{Evaluation of TH-Cre knock-in cell lines for detection and specific targeting of stem cell-derived dopaminergic neurons}},
  url          = {{https://lup.lub.lu.se/search/files/100827540/FIORENZANO_PDF_publication_in_heliyon.pdf}},
  doi          = {{10.1016/j.heliyon.2021.e06006}},
  volume       = {{7}},
  year         = {{2021}},
}