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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

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

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Autor(es):
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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]
Número total de Autores: 18
Afiliação do(s) autor(es):
[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
Número total de Afiliações: 9
Tipo de documento: Artigo Científico
Fonte: STEM CELL RESEARCH & THERAPY; v. 9, NOV 9 2018.
Citações Web of Science: 5
Resumo

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)

Processo FAPESP: 11/50542-9 - Estudo das neuroesferas de glioblastoma humano e a relação quimiotática com células-tronco mesenquimais
Beneficiário:Lorena Favaro Pavon Porfirio
Linha de fomento: Auxílio à Pesquisa - Regular