Migration of mouse-induced pluripotent stem cells to glioma-conditioned medium is mediated by tumor-associated specific growth factors

Abstract

Abstract. Neural and mesenchymal stem cells have extensive tropism for malignant glioma. The tumor tropism of induced pluripotent stem (iPS) cells was tested using the Matrigel invasion assay. Mouse iPS cells showed a significant tropism to the conditioned media prepared from six rodent and human glioma cell lines and this tropism to the glioma conditioned media was partially blocked by the neutralizing antibodies for four major tumor-associated growth factors [stem cell factor (SCF), platelet-derived growth factor BB (PDGF-BB), stromal-derived factor-1α (SDF-1α) and vascular endothelial growth factor (VEGF)], which are secreted from the malignant gliomas. The tropism of the iPS cells was enhanced by the growth factors in a concentration-dependent manner from 0.1 to 100 ng/ml. The receptors for those growth factors (c-Kit, ICAM-1, CXCR4 and VEGFR2), measured by reverse transcriptase-polymerase chain reaction, were highly up-regulated in the mouse iPS cells compared to the mouse fibroblasts. The results showed that the specific growth factors secreted from the gliomas strongly attracted the iPS cells. Therefore, gene therapies using iPS cells as vectors to deliver anti-tumor agents are novel strategies for the treatment of malignant gliomas that deeply infiltrate the brain.

Genetically Engineered Multilineage-Differentiating Stress-Enduring Cells as Cellular Vehicles against Malignant Gliomas

“…The in vitro migratory capacity of Muse-tk cells toward brain tumor cells was also examined using a Matrigel invasion assay and conditioned medium (CM) of U87 and U251 cells in the lower chamber 31 . Only Muse-tk cells, and not non-Muse-tk cells (fibroblasts other than Muse cells, namely SSEA-3 − cells, which were introduced with tk), migrated to the lower chamber filled with CM of U87 and U251 cells (Figures 6B and 6C).…”

Stem cell-based therapies for cancer treatment: separating hope from hype

“…Various chemokine–chemokine receptor pairs have been associated with tumour tropism, and perhaps the best studied is stromal cell-derived factor 1 (SDF1; also known as CXCL12) and its receptor CXC-chemokine receptor 4 (CXCR4). To date, the SDF1–CXCR4 signalling axis has been shown to have a major role in the migration of multiple SC types, including adult SCs 17–20 , embryonic SCs (ESCs) 21 and induced pluripotent SCs (iPSCs) 22 . Other influential signalling pathways have been elucidated and include PI3K signalling 23 , urokinase-type plasminogen activator (uPA)–uPA receptor (uPAR) 24,25 , vascular endothelial growth factor receptor 2 (VEGFR2) 26 and matrix metalloproteinase 1 (MMP1)–proteinase-activated receptor 1 (PAR1) 27 .…”

Stem cells in cancer therapy: opportunities and challenges

“…A variety of MSC-expressed chemokine and growth factor receptors may participate in tumor homing [ 18 ]. The stromal cell-derived factor 1 (SDF1)/CXCR4 axis plays a major role in the migration of various stem cells [ 19 – 21 ]. To improve directed homing, stem cells have been engineered with higher levels of chemokine receptors, or target tissues have been manipulated to release more chemokines [ 22 ].…”