| Full text | |
| Author(s): Show less - |
Pavon, Lorena Favaro
[1, 2]
;
Sibov, Tatiana Tais
[1]
;
de Souza, Andrea Vieira
[3]
;
da Cruz, Edgar Ferreira
[4]
;
Malheiros, Suzana M. F.
[1]
;
Cabral, Francisco Romero
[3]
;
de Souza, Jean Gabriel
[5, 6]
;
Boufleur, Pamela
[5, 6]
;
de Oliveira, Daniela Mara
[7]
;
Caminada de Toledo, Silvia Regina
[8]
;
Marti, Luciana C.
[3]
;
Malheiros, Jackeline Moraes
[9]
;
Paiva, Fernando F.
[9]
;
Tannus, Alberto
[9]
;
de Oliveira, Sergio Mascarenhas
[9]
;
Chudzinski-Tavassi, Ana Marisa
[5, 6]
;
de Paiva Neto, Manoel A.
[1]
;
Cavalheiro, Sergio
[1]
Total Authors: 18
|
| Affiliation: | [1] Univ Fed Sao Paulo, Dept Neurosurg, Sao Paulo - Brazil
[2] Univ Fed Sao Paulo, Lab Cellular & Mol Neurosurg, Rua Napoleao Barros, 626 Vila Clementino, BR-04024002 Sao Paulo, SP - Brazil
[3] Hosp Israelita Albert Einstein, Expt Res Ctr, Sao Paulo - Brazil
[4] Univ Fed Sao Paulo, Discipline Nephrol, Sao Paulo - Brazil
[5] Butantan Inst, Lab Mol Biol, Sao Paulo - Brazil
[6] Butantan Inst, CENTD, Sao Paulo - Brazil
[7] Univ Brasilia, Dept Genet & Morphol, Brasilia, DF - Brazil
[8] Univ Fed Sao Paulo, Grp Apoio Adolescente & Crianca Com Canc GRAACC, Pediat Oncol Inst, Sao Paulo - Brazil
[9] Univ Sao Paulo, Sao Carlos Inst Phys, Sao Carlos, SP - Brazil
Total Affiliations: 9
|
| Document type: | Journal article |
| Source: | STEM CELL RESEARCH & THERAPY; v. 9, NOV 9 2018. |
| Web of Science Citations: | 5 |
| Abstract | |
BackgroundPrevious 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/resultsWe 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 (705nm), 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.ConclusionsTherefore, 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. (AU) | |