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Translational and Clinical Research
Article first published online: 28 APR 2010
Copyright © 2010 AlphaMed Press
Volume 28, Issue 6, pages 1107–1115, June 2010
How to Cite
Ramos, C. A., Asgari, Z., Liu, E., Yvon, E., Heslop, H. E., Rooney, C. M., Brenner, M. K. and Dotti, G. (2010), An Inducible Caspase 9 Suicide Gene to Improve the Safety of Mesenchymal Stromal Cell Therapies. STEM CELLS, 28: 1107–1115. doi: 10.1002/stem.433
C.A.R.: conception and design, collection and/or assembly of data, data analysis and interpretation, manuscript writing; Z.A.: collection and/or assembly of data; E.L.: collection and/or assembly of data; E.Y.: provision of study material; H.E.H.: conception and design; C.M.R.: conception and design; M.K.B.: conception and design, manuscript writing; G.D.: conception and design, provision of study material, manuscript writing.
Disclosure of potential conflicts of interest is found at the end of this article.
First published online in STEM CELLS EXPRESS April 28, 2010.
- Issue published online: 8 JUN 2010
- Article first published online: 28 APR 2010
- Accepted manuscript online: 28 APR 2010 12:00AM EST
- Manuscript Accepted: 15 APR 2010
- Manuscript Received: 1 SEP 2009
- Specialized Centers for Cell-Based Therapy Grant NIH-NHLBI. Grant Number: 1 U54 HL081007
- (Baylor College of Medicine). Grant Number: AP20187
- Mesenchymal stromal cells;
- Suicide gene;
- Caspase 9
Mesenchymal stromal cells (MSCs) have been infused in hundreds of patients to date, with minimal reported side effects. However, follow-up is limited and long-term side effects are unknown. Because several animal models have raised safety concerns, we sought to develop a system allowing control over the growth and survival of MSCs used therapeutically. We have previously described a suicide system based on an inducible caspase-9 (iCasp9) protein that is activated using a specific chemical inducer of dimerization (CID), analogs of which have been safely tested in a phase I study. Here, we show that MSCs can be easily transduced with this system and selected to high purity (greater than 97%) with clinical grade immunomagnetic procedures. The transduced cells maintain their basic physiology, including expression of surface antigens (such as positivity for CD73, CD90, and CD105, and negativity for hematopoietic markers) and their potential to differentiate into diverse connective tissue lineages (adipocytes, osteoblasts, and chondroblasts). Those cells and their differentiated progeny can be selectively eliminated in vitro or in vivo within 24 hours after exposure to pharmacological levels of CID, with evidence of apoptosis in more than 95% of iCasp9-positive cells. In conclusion, we have developed directed MSC killing to provide a necessary safety mechanism for therapies using progenitor cells. We believe that this approach will become of increasing value as clinical applications for MSCs develop further. STEM Cells 2010;28:1107–1115