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

Bourgine, P. and LeMagnen, C. and Pigeot, S. and Geurts, J. and Scherberich, A. and Martin, I.. (2014) Combination of immortalization and inducible death strategies to generate a human mesenchymal stromal cell line with controlled survival. Stem Cell Research, 12 (2). pp. 584-598.

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Official URL: http://edoc.unibas.ch/dok/A6223362

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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 (< 280PD) 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.
Faculties and Departments:03 Faculty of Medicine > Bereich Operative Fächer (Klinik) > Ehemalige Einheiten Operative Fächer (Klinik) > Orthopädie (Valderrabano)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Operative Fächer (Klinik) > Ehemalige Einheiten Operative Fächer (Klinik) > Orthopädie (Valderrabano)
UniBasel Contributors:Geurts, Jeroen and Scherberich, Arnaud
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Elsevier
ISSN:1873-5061
e-ISSN:1876-7753
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:09 Oct 2017 11:29
Deposited On:23 May 2014 08:34

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