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Prepublished online as a Blood First Edition Paper on July 24, 2003; DOI 10.1182/blood-2003-04-1193.
Submitted April 28, 2003
Accepted July 9, 2003
Immunosuppressive effect of mesenchymal stem cells favors tumor growth in allogeneic animals
Farida Djouad, Pascale Plence, Claire Bony, Philippe Tropel, Florence Apparailly, Jacques Sany, Daniele Noel*, and Christian Jorgensen
Immunopathologie des Maladies Tumorales et Auto-immunes, INSERM, Unite 475, Montpellier, France
Neurosciences Precliniques, INSERM, Unite 318, La Tronche, France
Service d'Immuno-Rhumatologie, Hopital Lapeyronie, Montpellier, France
* Corresponding author; email: noel{at}montp.inserm.fr.
Mesenchymal stem cells (MSCs) are largely studied for their potential clinical use. Recently, they have gained further interest after demonstration of an immunosuppressive role. In this study, we investigated whether in vivo injection of MSCs could display side effects related to systemic immunosuppression favoring tumor growth. We first showed in vitro that the murine C3H10T1/2 (C3) MSC line and primary MSCs exhibit immunosuppressive properties in mixed lymphocyte reaction. We demonstrated that this effect is mediated by a soluble factor(s), secreted only upon "activation" of MSCs in presence of splenocytes. Moreover, the immunosuppression is mediated by CD8+ regulatory cells responsible for the inhibition of allogeneic lymphocyte proliferation. We then demonstrated that the C3 MSCs expressing the hBMP-2 differentiation factor, were not rejected when implanted in various allogeneic immunocompetent mice and were still able to differentiate into bone. Importantly, using a murine melanoma tumor model, we showed that the sub-cutaneous injection of B16 melanoma cells led to tumor growth in allogeneic recipients only when MSCs were co-injected. Although the potential side effects of the immunosuppression induced by MSCs have to be taken into account in further clinical studies, the usefulness of MSCs for various therapeutic applications still remains of great interest.
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