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Carcinogenesis Advance Access published online on October 9, 2008
Carcinogenesis, doi:10.1093/carcin/bgn234
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© The Author 2008. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Development of sarcomas in mice implanted with mesenchymal stem cells seeded onto bioscaffolds

Roberta Tasso1,2, Andrea Augello1,2, Michela Carida'1,2, Fabio Postiglione1,2, Maria Grazia Tibiletti3, Barbara Bernasconi3, Simonetta Astigiano4, Franco Fais5, Mauro Truini6, Ranieri Cancedda1,2 and Giuseppina Pennesi1,2,*

1 Department of Oncology, Biology, and Genetics, University of Genova
2 Laboratory of Regenerative Medicine, National Cancer Research Institute, Largo Rosanna Benzi 10, 16132 Genova, Italy
3 Department of Pathology, Ospedale di Circolo, Viale Borri 57, 20121 Varese, Italy
4 Embryogenesis and Tumorigenesis in Animal Models, National Cancer Research Institute, Largo Rosanna Benzi 10, 16132 Genova, Italy
5 Department of Experimental Medicine, University of Genova, Via Leon Battista Alberti 2, 16132 Genova, Italy
6 Department of Diagnostic Technologies, National Cancer Research Institute, Largo Rosanna Benzi 10, 16132 Genova, Italy

Corresponding Author: Dr Giuseppina Pennesi, MD, PhD, Stem Cells Laboratory, Advanced Biotechnology Center, Largo Rosanna Benzi 10, 16132 Genova, Italy, Phone: +39-010-5737511, Fax: +39-010-5737505, e-mail: pina.pennesi{at}istge.it

Bone marrow-derived mesenchymal stem cells (MSC) are precursors of bone, cartilage, and fat tissue. MSC can also regulate the immune response. For these properties, they are tested in clinical trials for tissue repair in combination with bioscaffolds, or injected as cell suspension for immunosuppressant therapy. Experimental data, however, indicate that MSC can undergo or induce a tumorigenic process in determined circumstances.

We used a modified model of ectopic bone formation in mice by subcutaneously implanting porous ceramic seeded with murine MSC. In this new model, host-derived sarcomas developed when we implanted MSC/bioscaffold constructs into syngenic and immunodeficient recipients, but not in allogenic hosts or when MSC were injected as cell suspensions.

The bioscaffold provided a tri-dimensional support for MSC to aggregate, thus producing the stimulus for triggering the process eventually leading to the transformation of surrounding cells and creating a surrogate tumor stroma. The chemical and physical characteristics of the bioscaffold did not affect tumor formation; sarcomas developed either when a stiff porous ceramic was used, or when the scaffold was a smooth collagen sponge.

The immunoregulatory function of MSC contributed to tumor development. Implanted MSC expanded clones of CD4+CD25+ T regulatory lymphocytes that suppressed host's anti-tumor immune response.

Key Words: Mesenchymal stem cells • sarcoma • immune escape • regulatory T lymphocyte • tumor stroma

* Dr. Pennesi current address: Stem Cells Laboratory, Advanced Biotechnology Center, Largo Rosanna Benzi 10, 16132 Genova, Italy

Received May 12, 2008; revised September 11, 2008; accepted October 3, 2008.


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