Therapeutic potential of synovial fluid-derived mesenchymal stem cells by tropism for gliomas

Abstract

Mesenchymal stem cells (MSCs) are especially known to migrate toward glioma1. Gliomas are the most common malignant primary brain tumors. Many types of stem cells have been reported to have migration ability toward glioma1-4. These invasive tumor cells are inaccessible to current therapeutic strategies5. Using migration characteristic, human mesenchymal stem cell be used as a potential drug vehicle for the treatment of glioma5. However, There is no research on the comparison between three kinds of mesenchymal stem cells (Bone marrow derived-mesenchymal stem cells (BMMSCs), Adipose derived-mesenchymal stem cell (ADMSCs), Synovial fluid derived-mesenchymal stem cell (SFMSCs)) and the mechanisms underlying the tropism of mesenchymal stem cells (BMMSCs, ADMSCs, SFMSCs) for glioma remain poorly defined. Therefore we hypothesized that human synovial fluid-derived mesenchymal stem cell may migrate like BMMSC and ADMSC toward human glioma cell. And All the MSCs showed a significantly increase migratory capacity toward glioma in vitro and in vivo injection of NIR-675-labeled MSCs into the tumor mass of established human luc-U87-glioma in nude mice5. Furthermore, SFMSCs responds to cytokine stimulus from glioma that is known to secret a variety of chemokines, including Macrophage chemoattractant protein-1 (MCP-1), stromal cell-derived factor-1α (SDF-1α), regulated and normal T cell expressed and secreted (RANTES) and interleukin-8(IL-8). The receptors (CCR2, CXCR4, CCR5, CXCR2) of chemokines which are secreted by glioma are expected that those are expressed in MSCs. Moreover cytokines those are secreted by glioma affect to MSCs adhesion related molecules6,7: CD44,CD49a which lead to the change of the CD44 targeted- miR-133a-3p and CD49a targeted-miR-124a-5p on MSCs. MicroRNA target adhesion related molecules (CD44 and CD49)8, which are highly important molecules migration of cells.