In this study, the authors engineered BMP4-secreting mesenchymal stem cells to study their effect on a glioblastoma mouse model.
Glioblastoma is the most common primary intracranial malignant cancer in adults, and is associated with poor outcomes despite multimodality therapy. This lack of effectiveness of current therapies is presumably because of a small subset of tumor cells, so-called brain tumor initiating cells (BTIC), with self-renewal capabilities and stronger tumor-initiating capacities. Mesenchymal stem cells (MSC) have an endogenous tropism toward certain cancers, and adipose tissue provides a feasible and less invasive source of MSCs. Moreover, bone morphogenetic protein (BMP4) has been shown to decrease proliferation by inducing BTIC differentiation. Therefore, adipose-derived MSCs engineered to secrete BMP4 (hAMSCs-BMP4) may be a potential effective treatment option for glioblastoma.
In this study, we show that engineered hAMSC-BMP4 cells reduce the proliferation and migration of glioblastoma and induce differentiation of BTICs in vitro
and in vivo
. Furthermore, a single, cardiac injection of these cells into a mouse model of glioblastoma significantly prolongs survival. These findings suggest that hAMSCs-BMP4 are a promising novel cell-based therapy for patients with glioblastoma and potentially other metastatic cancers.
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Source: Clinical Cancer Research