Stem Cell Research & Therapy (Nov 2018)

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

  • 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

DOI
https://doi.org/10.1186/s13287-018-1049-0
Journal volume & issue
Vol. 9, no. 1
pp. 1 – 13

Abstract

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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.

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