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Background  Currently, there are many promising clinical trials using mesenchymal stem cells (MSCs) in cell-based therapies of numerous diseases. Increasingly, however, there is a concern over the use of MSCs because they home to tumors and can support tumor growth and metastasis. For instance, we established that MSCs in the ovarian tumor microenvironment promoted tumor growth and favored angiogenesis. In parallel studies, we also developed a new approach to induce the conventional mixed pool of MSCs into two uniform but distinct phenotypes we termed  MSC1  and  MSC2 .    Methodology/Principal Findings  Here we tested the  in vitro  and  in vivo  stability of  MSC1  and  MSC2  phenotypes as well as their effects on tumor growth and spread.  In vitro  co-culture of  MSC1  with various cancer cells diminished growth in colony forming units and tumor spheroid assays, while conventional MSCs or  MSC2  co-culture had the opposite effect in these assays. Co-culture of  MSC1  and cancer cells also distinctly affected their migration and invasion potential when compared to MSCs or  MSC2  treated samples. The expression of bioactive molecules also differed dramatically among these samples.  MSC1 -based treatment of established tumors in an immune competent model attenuated tumor growth and metastasis in contrast to MSCs- and  MSC2 -treated animals in which tumor growth and spread was increased. Also, in contrast to these groups,  MSC1 -therapy led to less ascites accumulation, increased CD45+leukocytes, decreased collagen deposition, and mast cell degranulation.    Conclusion/Significance  These observations indicate that the  MSC1  and  MSC2  phenotypes may be convenient tools for the discovery of critical components of the tumor stroma. The continued investigation of these cells may help ensure that cell based-therapy is used safely and effectively in human disease.

Mesenchymal Stem Cell 1 (MSC1)-Based Therapy Attenuates Tumor Growth Whereas MSC2-Treatment Promotes Tumor Growth and Metastasis