Brain engraftment and therapeutic potential of stem/progenitor cells derived from mouse skin

Patrizia Tunici, Jeff W M Bulte, Maria Grazia Bruzzone, Pietro Luigi Poliani, Laura Cajola, Marina Grisoli, Trevor Douglas, Gaetano Finocchiaro

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)506-513
Number of pages8
JournalJournal of Gene Medicine
Volume8
Issue number4
DOIs
Publication statusPublished - Apr 2006

Keywords

  • Brain tumors
  • Interleukin-4
  • Magnetic resonance imaging
  • Neural stem cells
  • Skin progenitor cells
  • Superparamagnetic iron oxide

ASJC Scopus subject areas

  • Genetics

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