Combination of immortalization and inducible death strategies to generate a human mesenchymal stromal cell line with controlled survival
Bourgine, Paul LU
; Le Magnen, Clementine
; Pigeot, Sebastien
; Geurts, Jeroen
; Scherberich, Arnaud
and Martin, Ivan
(2014)
In Stem Cell Research
12(2).
p.584-598
- Abstract
- The hTERT-immortalization of human bone marrow-derived Mesenchymal Stromal Cells (hMSCs) was proposed to address availability/standardization issues for experimental or clinical studies, but raised concerns due to possible uncontrolled growth or malignant cell transformation. Here we report a method to generate a hMSCs line with controlled survival, through the implementation of a pre-established suicide system (inducible caspase 9, iCasp9) in hTERT-transduced hMSCs.
Primary hMSCs were successfully immortalized (> 280 PD) and further transduced with the iCasp9 device. A clone was selected and shown to maintain typical properties of primary hMSCs, including phenotype, differentiation and immunomodulation capacities. The successive... (More) - The hTERT-immortalization of human bone marrow-derived Mesenchymal Stromal Cells (hMSCs) was proposed to address availability/standardization issues for experimental or clinical studies, but raised concerns due to possible uncontrolled growth or malignant cell transformation. Here we report a method to generate a hMSCs line with controlled survival, through the implementation of a pre-established suicide system (inducible caspase 9, iCasp9) in hTERT-transduced hMSCs.
Primary hMSCs were successfully immortalized (> 280 PD) and further transduced with the iCasp9 device. A clone was selected and shown to maintain typical properties of primary hMSCs, including phenotype, differentiation and immunomodulation capacities. The successive transductions did not induce tumorigenic transformation, as assessed by analysis of cell cycle regulators and in vivo luciferase-based cell tracking. Cells could be efficiently induced toward apoptosis (> 95%) both in vitro and in vivo.
By combining the opposite concepts of ‘induced-life’ and ‘inducible-death’, we generated a hMSCs line with defined properties and allowing for temporally controlled survival. The cell line represents a relevant tool for medical discovery in regenerative medicine and a potential means to address availability, standardization and safety requirements in cell & gene therapy. The concept of a hTERT-iCasp9 combination, here explored in the context of hMSCs, could be extended to other types of progenitor/stem cells. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/9276ce8c-622f-4e6b-b0a5-b0647b221975
- author
- Bourgine, Paul
LU
; Le Magnen, Clementine
; Pigeot, Sebastien
; Geurts, Jeroen
; Scherberich, Arnaud
and Martin, Ivan
- publishing date
- 2014
- type
- Contribution to journal
- publication status
- published
- in
- Stem Cell Research
- volume
- 12
- issue
- 2
- pages
- 584 - 598
- publisher
- Elsevier
- external identifiers
-
- scopus:84894275930
- ISSN
- 1876-7753
- DOI
- 10.1016/j.scr.2013.12.006
- language
- English
- LU publication?
- no
- id
- 9276ce8c-622f-4e6b-b0a5-b0647b221975
- date added to LUP
- 2022-02-09 19:08:16
- date last changed
- 2022-04-28 00:16:48
@article{9276ce8c-622f-4e6b-b0a5-b0647b221975,
abstract = {{The hTERT-immortalization of human bone marrow-derived Mesenchymal Stromal Cells (hMSCs) was proposed to address availability/standardization issues for experimental or clinical studies, but raised concerns due to possible uncontrolled growth or malignant cell transformation. Here we report a method to generate a hMSCs line with controlled survival, through the implementation of a pre-established suicide system (inducible caspase 9, iCasp9) in hTERT-transduced hMSCs.<br/>Primary hMSCs were successfully immortalized (> 280 PD) and further transduced with the iCasp9 device. A clone was selected and shown to maintain typical properties of primary hMSCs, including phenotype, differentiation and immunomodulation capacities. The successive transductions did not induce tumorigenic transformation, as assessed by analysis of cell cycle regulators and in vivo luciferase-based cell tracking. Cells could be efficiently induced toward apoptosis (> 95%) both in vitro and in vivo.<br/>By combining the opposite concepts of ‘induced-life’ and ‘inducible-death’, we generated a hMSCs line with defined properties and allowing for temporally controlled survival. The cell line represents a relevant tool for medical discovery in regenerative medicine and a potential means to address availability, standardization and safety requirements in cell & gene therapy. The concept of a hTERT-iCasp9 combination, here explored in the context of hMSCs, could be extended to other types of progenitor/stem cells.}},
author = {{Bourgine, Paul and Le Magnen, Clementine and Pigeot, Sebastien and Geurts, Jeroen and Scherberich, Arnaud and Martin, Ivan}},
issn = {{1876-7753}},
language = {{eng}},
number = {{2}},
pages = {{584--598}},
publisher = {{Elsevier}},
series = {{Stem Cell Research}},
title = {{Combination of immortalization and inducible death strategies to generate a human mesenchymal stromal cell line with controlled survival}},
url = {{http://dx.doi.org/10.1016/j.scr.2013.12.006}},
doi = {{10.1016/j.scr.2013.12.006}},
volume = {{12}},
year = {{2014}},
}