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

Stem Cell Research & Therapy

Daniela Mara de Oliveira¹  Suzana M. F. Malheiros²  Tatiana Tais Sibov²  Manoel A. de Paiva Neto²  Sérgio Cavalheiro²  Lorena Favaro Pavon²  Edgar Ferreira da Cruz³  Francisco Romero Cabral⁴  Luciana C. Marti⁴  Andrea Vieira de Souza⁴  Ana Marisa Chudzinski-Tavassi⁵  Pamela Boufleur⁵  Jean Gabriel de Souza⁵  Silvia Regina Caminada de Toledo⁶  Jackeline Moraes Malheiros⁷  Fernando F. Paiva⁷  Sérgio Mascarenhas de Oliveira⁷  Alberto Tannús⁷ 

[1] Department of Genetics and Morphology, University of Brasília;Department of Neurosurgery, Federal University of São Paulo;Discipline of Nephrology, Federal University of São Paulo;Experimental Research Center, Hospital Israelita Albert Einstein;Laboratory of Molecular Biology, Butantan Institute;Pediatric Oncology Institute, Grupo de Apoio ao Adolescente e à Criança com Câncer (GRAACC), Federal University of São Paulo;São Carlos Institute of Physics, São Paulo University;

关键词: CD133+ cells;    MSCs;    Tropism;    Chemokines;    Experimental model;    Exosomes;   

DOI  :  10.1186/s13287-018-1049-0

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown