Evaluation of TH-Cre knock-in cell lines for detection and specific targeting of stem cell-derived dopaminergic neurons
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/fe64e2bb-968f-4ed0-a244-022fdbc1fe03
- author
- Fiorenzano, Alessandro LU ; Birtele, Marcella LU ; Wahlestedt, Jenny Nelander LU and Parmar, Malin LU
- organization
-
- MultiPark: Multidisciplinary research focused on ParkinsonĀ“s disease
- Developmental and Regenerative Neurobiology (research group)
- StemTherapy: National Initiative on Stem Cells for Regenerative Therapy
- Stem Cell Center
- Wallenberg Neuroscience Centre, Lund
- Regeneration in Movement Disorders (research group)
- Neurology, Lund
- publishing date
- 2021-01
- 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
-
- pmid:33532642
- scopus:85100186345
- 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
- 2024-09-19 16:18:29
@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}}, }