31-07-08(18:13:07)
Authors:
Schmidt NO 1; Hansen, K 1; Laurent LC 2; Schwartz P 3; McKercher S 4; Lee JP 4/5; Lamszus K 1; Westphal M 1; Loring, J 2; Mueller FJ 2,6
Institutions:
1. Department of Neurosurgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
2. Center for Regenerative Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
3. Children’s Hospital of Orange County Research Institute, Orange, California 92826, USA.
4. Stem Cell & Regeneration Program, Center for Neuroscience and Aging Research, Burnham Institute for Medical Research, La Jolla, California 92037, USA.
5. Department of Pediatrics, University of California San Diego, School of Medicine, La Jolla, California 92093, USA.3.
6. Center for Psychiatry and Psychotherapy, University Hospital Schleswig Holstein, Niemannsweg 147, D-24105 Kiel, Germany
Title of abstract : The Adult Human Brain Contains a Unique Population of Highly Motile Neural Progenitors
Abstract text:
Neural stem and progenitor cells have been shown to be useful for cell replacement and neuroprotective strategies in various neuropathological conditions. While the adult human brain contains populations of neural progenitors, their lineage identity, their role in normal brain function, and their clinical potential remain to be evaluated. We obtained highly proliferative human neural progenitors (HANSE cells) from surgical specimens obtained at amygdalohippocampectomies (n=10) and resection of cerebral arteriovenous malformations (n=2). Different anatomical regions were prepared separately and a total of 39 different cultures were established. (mean patient age: 32 years, range 24-46). HANSE cells expressed stem cell markers like nestin, SOX2, BMI1, and musashi , and displayed multipotent differentiation and targeted migration patterns in glioblastoma xenograft models. Comprehensive functional genomics profiling of mRNA and microRNA phenotypes was interpreted in the context of diverse pluripotent and multipotent stem cell preparations (n=219). Unsupervised machine learning algorithms for global sample clustering and prediction of differentially-active protein networks were used to a) identify cell lineage relationships and b) define molecular pathways responsible for unique cell type functions. Our data indicate that the adult human brain contains a unique population of neural progenitor cells with significant responsiveness to brain malignancy. We found a surprising heterogeneity among genome-wide transcriptional phenotypes of in vitro neural progenitor cell preparations that are currently believed to be sufficiently identified with the term “neural stem cells”. Our findings put into question current prevalent stem cell identification strategies such as marker based selection or commonly used in vitro assays.
