Human umbilical cord blood stem cells show PDGF-D-dependent glioma cell tropism in vitro and in vivo.

Abstract

Despite advances in clinical therapies and technologies, the prognosis for patients with malignant glioma is poor. Neural stem cells (NSCs) have a chemotactic tropism toward glioma cells. The use of NSCs as carriers of therapeutic agents for gliomas is currently being explored. Here, we demonstrate that cells isolated from the umbilical cord blood show mesenchymal characteristics and can differentiate to adipocytes, osteocytes, and neural cells and show tropism toward cancer cells. We also show that these stem cells derived from the human umbilical cord blood (hUCB) induce apoptosis-like cell death in the glioma cell line SNB19 via Fas-mediated caspase-8 activation. From our glioma tropism studies, we have observed that hUCB cells show tropism toward glioma cells in vitro, in vivo, and ex vivo. We determined that this migration is partially dependent on the expression levels of platelet-derived growth factor (PDGF)-D from glioma cells and have observed that local concentration gradient of PDGF-D is sufficient to cause migration of hUCB cells toward the gradient as seen from our brain slice cultures. In our animal experiment studies, we observed that intracranially implanted SNB19 green fluorescent protein cells induced tropism of the hUCB cells toward themselves. In addition, the ability of these hUCBs to inhibit established intracranial tumors was also observed. We also determined that the migration of stem cells toward glioma cells was partially dependent on PDGF secreted by glioma cells and that the presence of PDGF-receptor (PDGFR) on hUCB is required for migration. Our results demonstrate that hUCB are capable of inducing apoptosis in human glioma cells and also show that glioma tropism and hUCB tropism toward glioma cells are partially dependent on the PDGF/PGGFR system.

• Authors: Christopher S Gondi, Krishna Kumar Veeravalli, Bharathi Gorantla, Dzung H Dinh, Dan Fassett, Jeffrey D Klopfenstein, Meena Gujrati, Jasti S Rao
• Journal: Neuro-oncology (Neuro Oncol) Vol. 12 Issue 5 Pg. 453-65 (May 2010) ISSN: 1523-5866 [Electronic] England
• PMID: 20406896 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Lymphokines
• PDGFD protein, human
• Platelet-Derived Growth Factor
• Receptor, Platelet-Derived Growth Factor alpha

Topics

• Animals
• Apoptosis (physiology)
• Blotting, Western
• Brain Neoplasms (metabolism)
• Cell Movement (physiology)
• Cell Separation
• Fetal Blood (cytology)
• Flow Cytometry
• Glioma (metabolism)
• Humans
• Lymphokines (metabolism)
• Mice
• Multipotent Stem Cells (cytology, metabolism)
• Platelet-Derived Growth Factor (metabolism)
• Rats
• Receptor, Platelet-Derived Growth Factor alpha (metabolism)
• Spheroids, Cellular
• Tumor Cells, Cultured
• Xenograft Model Antitumor Assays