Effect of human skin-derived stem cells on vessel architecture, tumor growth, and tumor invasion in brain tumor animal models.
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 controlateral 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-beta1 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.
Pisati
Federica
F
Stem Cell Laboratory, Department of Neurological Science, Centro Dino Ferrari, University of Milan, Milan, Italy.
Belicchi
Marzia
M
Acerbi
Francesco
F
Marchesi
Chiara
C
Giussani
Carlo
C
Gavina
Manuela
M
Javerzat
Sophie
S
Hagedorn
Martin
M
Carrabba
Giorgio
G
Lucini
Valeria
V
Gaini
Sergio Maria
SM
Bresolin
Nereo
N
Bello
Lorenzo
L
Bikfalvi
Andreas
A
Torrente
Yvan
Y
D000818:Animals; D001932:Brain Neoplasms / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000098:blood supply; D005909:Glioblastoma / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008822:Mice, Transgenic; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D012867:Skin / Q000166:cytology*; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000502:physiology*; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis; D023041:Xenograft Model Antitumor Assays
D053773:Transforming Growth Factor beta1