The experimental investigation of glioma ⁃trophic capacity of human umbilical cord-derived mesenchymal stem cells after intraventricular administration

Abstract

Objective To explore the glioma⁃trophic migration capacity of human umbilical cord-derived mesenchymal stem cells (hUC⁃MSCs) by intraventricular administration. Methods The umbilical cord tissue were obtained during full-term pregnancy cesarean section under sterile conditions. This study was approved by Ethics Committee and got the informed consent of patient. The hUC-MSCs were isolated by trypsin and collagenase digestion, followed by adherent culture methods. The characteristics of isolated hUC-MSCs were demonstrated by cell morphylogy, phenotype analysis and multi-differentiation potentials into adipocytes, osteoblasts and neural cells. Then the hUC-MSCs were labeled with CM-DiI and injected into contralateral ventricle of glioma of the C6 glioma⁃bearing Sprague-Dawley (SD) rats. Two weeks later, the rats were sacrificed and the brains were taken out to examine the migration and distribution of hUC-MSCs in the tumor bed, at the interface of tumor and cerebral parenchyma as well as the tumor satelites infiltrating into the normal brain. Results The hUC-MSCs demonstrated plastic-adherent characterization and homogeneous fibroblastic-like morphylogy in culture, expression of specific surface phenotypes of MSCs (CD13, CD29, CD44, CD90) but not endothelial or hematopoietic markers (CD14, CD31, CD34, CD38, CD45, CD133), and muti-differentiatiation potentials into Oil red O stained adipocytes, Alizarin red S stained osteoblasts, neuron-specific enolase (NSE)-positive neurons and glial fibrillary acidic protein (GFAP)-positive astrocytes in permissive inducive conditions. Importantly, after labeled hUC-MSCs injection into contralateral ventricle of glioma, the hUC-MSCs migrated from initial injection site to the glioma mass and along the interface of tumor and brain, and some of them "chasing" the glioma satellites infiltrated into the normal parenchyma. Conclusion The hUC-MSCs possess prominent tumor-specific targeting capacity and extensive intratumoral distribution in glioma models. Thus, they may serve as novel vehicles in cell-based gene-therapy of glioma.