gms | German Medical Science

Objective: The transplantation of neural stem cells or the therapeutic modulation of the endogenous neural stem cell pool offers new potential for cell replacement strategies and for the delivery of gene therapy in various neurological diseases such as invasive gliomas. It is not entirely clear if the adult human brain contains populations of neural progenitors which can be exploited for the development of local brain tumor therapies. The aim of this study was the establishment and characterization of neural progenitor cells from the adult human brain as a model system for lineage analysis and for the assessment of their capabilities to target malignant glioma.

Methods: We modified previously reported protocols for establishing neural progenitor cultures. Cultures were extensively characterized using immunohistochemistry, RT-PCR, FACS analysis and differentiation assays. Global molecular profiling was performed by using Illumina Sentrix Whole Genome microarrays and analyzed in a database containing transcriptional profiles of a collection of biologically well-characterized cultured stem cell-associated samples (n=83). Tumor tropism of neural progenitors was assessed in vivo using the intracerebral U87- and G55-human glioblastoma models in nude mice.

Results: We obtained highly proliferative neuroectodermal cells from surgical specimen of amygdalohippocampectomies (n=10) and brain tissue adherent to resected arteriovenous malformations (n=2). Different anatomical regions were prepared separately and a total of 39 different cultures have been established (mean patient age 32 years, range 24-46). The cultures grew as homogenous monolayers of progenitor cells expressing stem cell markers like Nestin, A2B5, SOX2, BMI1, Musashi and infrequently CD133. They displayed a multipotent differentiation profile along neuronal, astroglial and oligodendroglial lineages. Based on the global gene expression pattern these neural progenitor cells were a cell class separate from well characterized fetal neural stem cell cultures. The neural progenitor cells displayed a directed migration towards intracerebral glioma and enhanced within the tumor mass when transplanted in the contralateral hemisphere of nude mice.

Conclusions: Our data indicates that the adult human brain contains a unique population of progenitor cells. Based on their extensive tumor tropism these cells may be able to serve as drug delivery vehicles to target invasive glioma cells. This study suggests an unexpected responsiveness of the adult human brain to the presence of a brain tumor which may open new possibilities for therapeutic strategies.