Effect of human skin-derived stem cells on vessel architecture, tumor growth, and tumor invasion in brain tumor animal models

Federica Pisati, Marzia Belicchi, Francesco Acerbi, Chiara Marchesi, Carlo Giussani, Manuela Gavina, Sophie Javerzat, Martin Hagedorn, Giorgio Carrabba, Valeria Lucini, Sergio Maria Gaini, Nereo Bresolin, Lorenzo Bello, Andreas Bikfalvi, Yvan Torrente

Research output: Contribution to journalArticlepeer-review

Abstract

Glioblastomas represent an important cause of cancer-related mortality with poor survival. Despite many advances, the mean survival time has not significantly improved in the last decades. New experimental approaches have shown tumor regression after the grafting of neural stem cells and human mesenchymal stem cells into experimental intracranial gliomas of adult rodents. However, the cell source seems to be an important limitation for autologous transplantation in glioblastoma. In the present study, we evaluated the tumor targeting and antitumor activity of human skin-derived stem cells (hSDSCs) in human brain tumor models. The hSDSCs exhibit tumor targeting characteristics in vivo when injected into the contralateral hemisphere or into the tail vein of mice. When implanted directly into glioblastomas, hSDSCs distributed themselves extensively throughout the tumor mass, reduced tumor vessel density, and decreased angiogenic sprouts. In addition, transplanted hSDSCs differentiate into pericyte cell and release high amounts of human transforming growth factor-β1 with low expression of vascular endothelial growth factor, which may contribute to the decreased tumor cell invasion and number of tumor vessels. In long-term experiments, the hSDSCs were also able to significantly inhibit tumor growth and to prolong animal survival. Similar behavior was seen when hSDSCs were implanted into two different tumor models, the chicken embryo experimental glioma model and the transgenic Tyrp1-Tag mice. Taken together, these data validate the use of hSDSCs for targeting human brain tumors. They may represent therapeutically effective cells for the treatment of intracranial tumors after autologous transplantation.

Original languageEnglish
Pages (from-to)3054-3063
Number of pages10
JournalCancer Research
Volume67
Issue number7
DOIs
Publication statusPublished - Apr 1 2007

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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