Tropism of mesenchymal stem cell toward CD133+ stem cell of glioblastoma in vitro and promote tumor proliferation in vivo

• Main Authors: Lorena Favaro Pavon, Tatiana Tais Sibov, Andrea Vieira de Souza, Edgar Ferreira da Cruz, Suzana M. F. Malheiros, Francisco Romero Cabral, Jean Gabriel de Souza, Pamela Boufleur, Daniela Mara de Oliveira, Silvia Regina Caminada de Toledo, Luciana C. Marti, Jackeline Moraes Malheiros, Fernando F. Paiva, Alberto Tannús, Sérgio Mascarenhas de Oliveira, Ana Marisa Chudzinski-Tavassi, Manoel A. de Paiva Neto, Sérgio Cavalheiro
• Format: Article
• Language: English
• Published: BMC 2018-11-01
• Series: Stem Cell Research & Therapy
• Subjects: CD133+ cells; MSCs; Tropism; Chemokines; Experimental model; Exosomes
• Online Access: http://link.springer.com/article/10.1186/s13287-018-1049-0

Abstract Background Previous studies have demonstrated remarkable tropism of mesenchymal stem cells (MSCs) toward malignant gliomas, making these cells a potential vehicle for delivery of therapeutic agents to disseminated glioblastoma (GBM) cells. However, the potential contribution of MSCs to tumor progression is a matter of concern. It has been suggested that CD133+ GBM stem cells secrete a variety of chemokines, including monocytes chemoattractant protein-1 (MCP-1/CCL2) and stromal cell-derived factor-1(SDF-1/CXCL12), which could act in this tropism. However, the role in the modulation of this tropism of the subpopulation of CD133+ cells, which initiate GBM and the mechanisms underlying the tropism of MSCs to CD133+ GBM cells and their effects on tumor development, remains poorly defined. Methods/results We found that isolated and cultured MSCs (human umbilical cord blood MSCs) express CCR2 and CXCR4, the respective receptors for MCP-1/CCL2 and SDF-1/CXCL12, and demonstrated, in vitro, that MCP-1/CCL2 and SDF-1/CXC12, secreted by CD133+ GBM cells from primary cell cultures, induce the migration of MSCs. In addition, we confirmed that after in vivo GBM tumor establishment, by stereotaxic implantation of the CD133+ GBM cells labeled with Qdots (705 nm), MSCs labeled with multimodal iron oxide nanoparticles (MION) conjugated to rhodamine-B (Rh-B) (MION-Rh), infused by caudal vein, were able to cross the blood-brain barrier of the animal and migrate to the tumor region. Evaluation GBM tumors histology showed that groups that received MSC demonstrated tumor development, glial invasiveness, and detection of a high number of cycling cells. Conclusions Therefore, in this study, we validated the chemotactic effect of MCP-1/CCL2 and SDF-1/CXCL12 in mediating the migration of MSCs toward CD133+ GBM cells. However, we observed that, after infiltrating the tumor, MSCs promote tumor growth in vivo probably by release of exosomes. Thus, the use of these cells as a therapeutic carrier strategy to target GBM cells must be approached with caution.