Brain engraftment and therapeutic potential of stem/progenitor cells derived from mouse skin.
Skin stem/progenitor cells (SKPs) derive from the dermis and in culture can generate mesodermal and neural progenies. To investigate their potential for the treatment of brain diseases, we first injected SKPs into the brain of syngeneic mice. Brain histology indicated that most SKPs remained undifferentiated and clustered at the injection site, while, in vitro, 17% of SKPs expressed neural markers, as assessed by flow cytometry. After labeling with magnetodendrimers, murine and human SKPs were detected by magnetic resonance imaging even 5 months after brain injection. To evaluate their therapeutic potential on malignant gliomas, IL-4 SKPs (i.e. SKPs transduced by a lentiviral vector carrying the cDNA of the anti-glioma cytokine interleukin-4) were injected into GL261 experimental gliomas. IL-4-SKPs prolonged significantly the survival of tumor-bearing mice: furthermore, GL261 gliomas attracted SKPs originally injected into the contralateral hemisphere. Thus, prolonged survival, capacity for transgene expression, and lack of uncontrolled proliferation suggest that SKPs warrant further consideration as therapeutic tools for brain tumors and, possibly, other neurological disorders.
Tunici
Patrizia
P
Unit of Experimental Neuro-Oncology, Istituto Nazionale Neurologico C. Besta, Milan, Italy.
Bulte
Jeff W M
JW
Bruzzone
Maria Grazia
MG
Poliani
Pietro Luigi
PL
Cajola
Laura
L
Grisoli
Marina
M
Douglas
Trevor
T
Finocchiaro
Gaetano
G
D000818:Animals; D015415:Biomarkers / Q000032:analysis; D001921:Brain / Q000378:metabolism; D001932:Brain Neoplasms / Q000276:immunology / Q000628:therapy*; D002465:Cell Movement; D005910:Glioma / Q000276:immunology / Q000628:therapy*; D006801:Humans; D015847:Interleukin-4 / Q000235:genetics; D016086:Lentivirus / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D012867:Skin / Q000166:cytology*; D033581:Stem Cell Transplantation
D015415:Biomarkers; D015847:Interleukin-4