gms | German Medical Science

Objective: Much effort has been put into establishing human multipotent cells as carriers for malignant glioma therapy. We already described VEGF-dependent interaction of adult human mesenchymal stem cells (hMSC) and glioma cells in vitro and characterized glioma-modulated invasive hMSC-behaviour glioma infiltrated brain in vivo. In this study, we evaluated the potential risks of adult hMSC in the use as a cellular vector for glioma therapy.

Methods: hMSC were isolated from bone marrow biopsies carried out for haematological indications. Primary hMSC were held under long-term conditioning in order to rule out genetic instability due to cell culture artifacts. Cells were grown with either glioma-conditioned or normal medium. To assess eventually acquired malignant potential, colony forming assays were performed and proliferation curves were documented. For in vivo assessment, cells were (i) implanted intracranially without any presence of glioma cells, (ii) administered locally in U373 glioma bearing nude rats, (iii) applied systemically in U373 glioma bearing nude rats.

Results: In vivo, we observed 1 case out of 40 cases, in which primary hMSC formed a tumor-like formation, surrounded by glioma cells. Under long-term culture conditions, most of the hMSC showed the well-known phenomenon of senescence (growth arrest). Out of a hMSC panel of 8 patients, 2 probes showed a sudden change of phenotype with a strong increase of proliferation after 8 weeks culture with glioma conditioned medium. These cells also exhibited a malignant phenotype in terms of intense colony forming in vitro.

Conclusions: Despite hMSC seem to be effective cellular carriers for anti-glioma therapy due to their strong glioma tropism, there is a risk of a malignant transformation of primary isolated hMSC after contact with glioma cells or even glioma-conditioned medium. This observation might have impact on the conception of future cell based therapies.