Mesenchymal stem cells overexpressing PEDF decrease the angiogenesis of gliomas.
The present study is an exploration of a novel strategy to target a therapeutic gene to brain tumour tissues. In the present study, we evaluated the feasibility of using hMSCs (human mesenchymal stem cells) to deliver PEDF (pigment epithelium-derived factor), a potent inhibitor of tumour angiogenesis, in a model of intracranial gliomas. To assess its potential of tracking gliomas, MSCs (mesenchymal stem cells) were injected into the cerebral hemisphere and it showed that MSCs infiltrated into the vessel beds and scattered throughout the tumour. In vitro migration assay showed that the VEGF (vascular endothelial growth factor) enhanced MSC migration. In contrast, the migratory activity of MSCs was significantly inhibited with the presence of PEDF. Systematic delivery of AAV (adeno-associated virus)-PEDF to established glioma xenografts resulted in increased apoptosis of gliomas. In addition, MSC-PEDF treatment prolonged the survival of mice bearing U87 gliomas. Taken together, these data validate that MSCs-PEDF can migrate and deliver PEDF to target glioma cells, which may be a novel and promising therapeutic approach for refractory brain tumour.
*Department of Neurology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, People's Republic of China.
Qiaoshu
Q
Wang
†Department of Endocrinology, Huashan Hospital, Fudan University, Shanghai 200040, People's Republic of China.
Zhaoyun
Z
Zhang
‡Department of Hematology, Huashan Hospital, Fudan University, Shanghai 200040, People's Republic of China.
Tianling
T
Ding
‡Department of Hematology, Huashan Hospital, Fudan University, Shanghai 200040, People's Republic of China.
Zi
Z
Chen
§Department of Laboratory Medicine, Huashan Hospital, Fudan University, Shanghai 200040, People's Republic of China.
Tao
T
Zhang
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D002465:Cell Movement / Q000235:genetics; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D009389:Neovascularization, Pathologic / Q000235:genetics* / Q000628:therapy; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D015843:Serpins / Q000235:genetics / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays; D000099174:Pigment Epithelium-Derived Factor
D005136:Eye Proteins; D009414:Nerve Growth Factors; D015843:Serpins; D042461:Vascular Endothelial Growth Factor A; D000099174:Pigment Epithelium-Derived Factor