Human Bone Marrow–Derived Mesenchymal Stem Cells in the Treatment of Gliomas
10.1158/0008-5472.can-04-1874
Crossref journal-article
American Association for Cancer Research (AACR)
Cancer Research (1086)
Abstract

AbstractThe poor survival of patients with human malignant gliomas relates partly to the inability to deliver therapeutic agents to the tumor. Because it has been suggested that circulating bone marrow–derived stem cells can be recruited into solid organs in response to tissue stresses, we hypothesized that human bone marrow–derived mesenchymal stem cells (hMSC) may have a tropism for brain tumors and thus could be used as delivery vehicles for glioma therapy. To test this, we isolated hMSCs from bone marrow of normal volunteers, fluorescently labeled the cells, and injected them into the carotid artery of mice bearing human glioma intracranial xenografts (U87, U251, and LN229). hMSCs were seen exclusively within the brain tumors regardless of whether the cells were injected into the ipsilateral or contralateral carotid artery. In contrast, intracarotid injections of fibroblasts or U87 glioma cells resulted in widespread distribution of delivered cells without tumor specificity. To assess the potential of hMSCs to track human gliomas, we injected hMSCs directly into the cerebral hemisphere opposite an established human glioma and showed that the hMSCs were capable of migrating into the xenograft in vivo. Likewise, in vitro Matrigel invasion assays showed that conditioned medium from gliomas, but not from fibroblasts or astrocytes, supported the migration of hMSCs and that platelet-derived growth factor, epidermal growth factor, or stromal cell–derived factor-1α, but not basic fibroblast growth factor or vascular endothelial growth factor, enhanced hMSC migration. To test the potential of hMSCs to deliver a therapeutic agent, hMSCs were engineered to release IFN-β (hMSC-IFN-β). In vitro coculture and Transwell experiments showed the efficacy of hMSC-IFN-β against human gliomas. In vivo experiments showed that treatment of human U87 intracranial glioma xenografts with hMSC-IFN-β significantly increase animal survival compared with controls (P < 0.05). We conclude that hMSCs can integrate into human gliomas after intravascular or local delivery, that this engraftment may be mediated by growth factors, and that this tropism of hMSCs for human gliomas can be exploited to therapeutic advantage.

Bibliography

Nakamizo, A., Marini, F., Amano, T., Khan, A., Studeny, M., Gumin, J., Chen, J., Hentschel, S., Vecil, G., Dembinski, J., Andreeff, M., & Lang, F. F. (2005). Human Bone Marrow–Derived Mesenchymal Stem Cells in the Treatment of Gliomas. Cancer Research, 65(8), 3307–3318.

Authors 12
  1. Akira Nakamizo (first)
  2. Frank Marini (additional)
  3. Toshiyuki Amano (additional)
  4. Asadullah Khan (additional)
  5. Matus Studeny (additional)
  6. Joy Gumin (additional)
  7. Julianne Chen (additional)
  8. Stephen Hentschel (additional)
  9. Giacomo Vecil (additional)
  10. Jennifer Dembinski (additional)
  11. Michael Andreeff (additional)
  12. Frederick F. Lang (additional)
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Dates
Type When
Created 8 years, 1 month ago (July 21, 2017, 6:43 p.m.)
Deposited 2 months, 1 week ago (June 24, 2025, 1:14 p.m.)
Indexed 5 days, 17 hours ago (Aug. 31, 2025, 6:38 a.m.)
Issued 20 years, 4 months ago (April 15, 2005)
Published 20 years, 4 months ago (April 15, 2005)
Published Online 20 years, 4 months ago (April 15, 2005)
Published Print 20 years, 4 months ago (April 15, 2005)
Funders 0

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@article{Nakamizo_2005, title={Human Bone Marrow–Derived Mesenchymal Stem Cells in the Treatment of Gliomas}, volume={65}, ISSN={1538-7445}, url={http://dx.doi.org/10.1158/0008-5472.can-04-1874}, DOI={10.1158/0008-5472.can-04-1874}, number={8}, journal={Cancer Research}, publisher={American Association for Cancer Research (AACR)}, author={Nakamizo, Akira and Marini, Frank and Amano, Toshiyuki and Khan, Asadullah and Studeny, Matus and Gumin, Joy and Chen, Julianne and Hentschel, Stephen and Vecil, Giacomo and Dembinski, Jennifer and Andreeff, Michael and Lang, Frederick F.}, year={2005}, month=apr, pages={3307–3318} }