Human adipose tissue-derived mesenchymal stem cells target brain tumor-initiating cells

Seung Ah Choi, Ji Yeoun Lee, Sung Eun Kwon, Kyu Chang Wang, Ji Hoon Phi, Jung Won Choi, Xiong Jin, Ja Yun Lim, Hyunggee Kim, Seung Ki Kim

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

In neuro-oncology, the biology of neural stem cells (NSCs) has been pursued in two ways: as tumor-initiating cells (TICs) and as a potential cell-based vehicle for gene therapy. NSCs as well as mesenchymal stem cells (MSCs) have been reported to possess tumor tropism capacities. However, there is little data on the migratory capacity of MSCs toward brain tumor-initiating cells (BTICs). This study focuses on the ability of human adipose tissue derived MSCs (hAT-MSCs) to target BTICs and their crosstalk in the microenvironment. BTICs were isolated from three different types of brain tumors. The migration capacities of hAT-MSCs toward BTICs were examined using an in vitro migration assay and in vivo bioluminescence imaging analysis. To investigate the crosstalk between hAT-MSCs and BTICs, we analyzed the mRNA expression patterns of cyto-chemokine receptors by RT-qPCR and the protein level of their ligands in co-cultured medium. The candidate cyto-chemokine receptors were selectively inhibited using siRNAs. Both in vitro and in vivo experiments showed that hAT-MSCs possess migratory abilities to target BTICs isolated from medulloblastoma, atypical teratoid/rhabdoid tumors (AT/RT) and glioblastoma. Different types of cyto-chemokines are involved in the crosstalk between hAT-MSCs and BTICs (medulloblastoma and AT/RT: CXCR4/SDF-1, CCR5/RANTES, IL6R/IL-6 and IL8R/IL8; glioblastoma: CXCR4/SDF-1, IL6R/IL-6, IL8R/IL-8 and IGF1R/IGF-1). Our findings demonstrated the migratory ability of hAT-MSCs for BTICs, implying the potential use of MSCs as a delivery vehicle for gene therapy. This study also confirmed the expression of hAT-MSCs cytokine receptors and the BTIC ligands that play roles in their crosstalk.

Original languageEnglish
Article numbere0129292
JournalPLoS One
Volume10
Issue number6
DOIs
Publication statusPublished - 2015 Jun 15

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Neoplastic Stem Cells
Stem cells
Mesenchymal Stromal Cells
Brain Neoplasms
adipose tissue
stem cells
Adipose Tissue
Tumors
Brain
Tissue
brain
Crosstalk
Medulloblastoma
neoplasms
gene therapy
Neural Stem Cells
Chemokine Receptors
Glioblastoma
Interleukin-8
interleukin-6

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Choi, S. A., Lee, J. Y., Kwon, S. E., Wang, K. C., Phi, J. H., Choi, J. W., ... Kim, S. K. (2015). Human adipose tissue-derived mesenchymal stem cells target brain tumor-initiating cells. PLoS One, 10(6), [e0129292]. https://doi.org/10.1371/journal.pone.0129292

Human adipose tissue-derived mesenchymal stem cells target brain tumor-initiating cells. / Choi, Seung Ah; Lee, Ji Yeoun; Kwon, Sung Eun; Wang, Kyu Chang; Phi, Ji Hoon; Choi, Jung Won; Jin, Xiong; Lim, Ja Yun; Kim, Hyunggee; Kim, Seung Ki.

In: PLoS One, Vol. 10, No. 6, e0129292, 15.06.2015.

Research output: Contribution to journalArticle

Choi, SA, Lee, JY, Kwon, SE, Wang, KC, Phi, JH, Choi, JW, Jin, X, Lim, JY, Kim, H & Kim, SK 2015, 'Human adipose tissue-derived mesenchymal stem cells target brain tumor-initiating cells', PLoS One, vol. 10, no. 6, e0129292. https://doi.org/10.1371/journal.pone.0129292
Choi, Seung Ah ; Lee, Ji Yeoun ; Kwon, Sung Eun ; Wang, Kyu Chang ; Phi, Ji Hoon ; Choi, Jung Won ; Jin, Xiong ; Lim, Ja Yun ; Kim, Hyunggee ; Kim, Seung Ki. / Human adipose tissue-derived mesenchymal stem cells target brain tumor-initiating cells. In: PLoS One. 2015 ; Vol. 10, No. 6.
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