Introduction: Glioblastoma(GB) is the most common adult primary intracranial cancer, and survival has not significantly changed recently. These tumors are thought to be maintained by a subpopulation of cells called glioma stem cells (GSCs). These cells are resistant to radiation and chemotherapy, making current treatment strategies ineffective. Human mesenchymal stem cells(hMSCs) have recently been found to exhibit brain tumor tropism, and proteins such as bone morphogenic protein 4 (BMP4) have been demonstrated to attenuate stem cells. Human adipose-derived MSCs(hAMSCs), a type of hMSCs, designed to secrete BMP4 may be a promising treatment option. This study aimed to evaluate the efficacy of engineered hAMSC-BMP4 in attenuating the migration and proliferation of GSCs, as well as evaluate the stability of these cells in the presence of GB in vitro and in vivo. These findings may eventually lead to a human clinical trial.
Methods: hAMSCs were purchased and engineered to secrete BMP4 by a retroviral vector system. GSCs were derived from intraoperative human GB tissue. In vitro migration assays consisted of transwell and microfluidic chambers, while in vitro proliferation assays were done using MTS and EdU assays. An in vivo murine tumor model was used to evaluate proliferation and migration.
Results: hAMSCs-BMP4 were able to induce differentiation, decrease proliferation, and reduce the migratory capacity of GSCs in vitro and in vivo. These cells were also able to target both the tumor bulk and migratory GB cells in vivo. Importantly, neither GB cells nor BMP4 modify hAMSC’s proliferation and differentiation.
Conclusions: This study demonstrates the potential efficacy of hAMSCs-BMP4 for GB treatment. These engineered cells are able to deliver anticancer proteins to both the tumor bulk and satellite cells. They are not changed by GB cells. These findings may potentially lead to human clinical trials.
Patient Care: Glioblastoma (GB) is the most common adult primary intracranial cancer, and survival has not significantly changed recently. We have developed a new way to treat patients with this disease that may improve outcomes.
Learning Objectives: To identify the role that mesenchymal stem cells that are engineered to secrete BMP4 have to glioblastoma stem cells.
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