Combination of immortalization and inducible death strategies to generate a human mesenchymal stromal cell line with controlled survival.

Détails

ID Serval
serval:BIB_3F6C4348904C
Type
Article: article d'un périodique ou d'un magazine.
Sous-type
Compte-rendu: analyse d'une oeuvre publiée.
Collection
Publications
Titre
Combination of immortalization and inducible death strategies to generate a human mesenchymal stromal cell line with controlled survival.
Périodique
Stem cell research
Auteur(s)
Bourgine P., Le Magnen C., Pigeot S., Geurts J., Scherberich A., Martin I.
ISSN
1876-7753 (Electronic)
ISSN-L
1873-5061
Statut éditorial
Publié
Date de publication
03/2014
Peer-reviewed
Oui
Volume
12
Numéro
2
Pages
584-598
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
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.
Mots-clé
Animals, Bone Marrow Cells/cytology, Bone Marrow Cells/metabolism, Cell Death/physiology, Cell Differentiation/physiology, Cell Growth Processes/physiology, Cells, Cultured, Female, Humans, Mesenchymal Stem Cells/cytology, Mesenchymal Stem Cells/metabolism, Mice, Mice, Inbred NOD, Mice, SCID, Middle Aged
Pubmed
Web of science
Open Access
Oui
Création de la notice
27/07/2020 18:55
Dernière modification de la notice
28/07/2020 6:26
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