Artikel
Human adult mesenchymal stem cells are recruited by malignant gliomas by secretion of SDF-1
Human adulte mesenchymale Stammzellen werden von malignen Gliomen durch SDF-1 Sekretion rekrutiert
Suche in Medline nach
Autoren
Veröffentlicht: | 30. Mai 2008 |
---|
Gliederung
Text
Objective: Aim of our study was to show whether human adult mesenchymal stem cells (hMSC) can be isolated from malignant glioma specimen, obtained from neurosurgical operations and to identify the role of stromal derived factor (SDF-1) as a contributing factor of their recruitment.
Methods: Glioma specimen of different grades (n=12) were included in our study. hMSCs were isolated by the use of a ficoll gradient. Isolated cells were intensively characterized by FACS-analysis as well as differentiation assays into mesenchymal lineages (fat, bone). SDF-1 was analyzed by ELISA in blood samples from glioma patients before and after administration of corticosteroids as an antiedematous therapy. SDF-1 was evaluated in the glioma tissue by qPCR. SDF-1 receptor (CXCR-4) expression of hMSC was analyzed.
Results: Only in high grade gliomas, by the use of intense FACS analysis, we found the cells isolated by our protocol to express typical surface markers of hMSCs and CXCR4, the receptor of SDF-1. Differentiation assays showed that the cells, although derived from malignant glioma tissue, exhibit differentiation potential into mesenchymal cell lines, producing fat or bone. Directed invasion of hMSC in vitro was increased in presence of a SDF-1 gradient. Malignant glioma tissue showed to overexpress SDF-1, compared to normal brain tissue, obtained from patients with epilepsy surgery. Serum-SDF-1 levels were elevated in patients with gliomas compared to healthy volunteers.
Conclusions: Malignant glioma tissue contains a progenitor cell type, resembling mesenchymal stem cell (hMSC) characteristics. This indicates active recruitment of these cells from the circulation by gliomas. As a possible mechanism for recruitment of hMSCs from bone marrow we identified the SDF-1 / CXCR4 system.