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von Campe, G.

Publications and source records attributed to von Campe, G..

2 recordsLinked to original sources

Human Biopsies in Nanofibrillar Cellulose Hydrogel - A Novel Method for Long-term Tissue Culture

Advanced 3D in vitro models are laborious to prepare and susceptible to unintentional design errors due to culture adaptations, cell immaturity, xenofactors or yet incomplete knowledge of the dynamics within tissues or materials. In order to acquire cost-efficient research material with intact in vivo composition, we developed novel tissue culture method with plant-derived scaffolding. Human skin-, foreskin- and glioblastoma multiforme biopsies were dissected mechanically and cultivated for 28 days in plant-derived nanofibrillar cellulose hydrogel. Comparative cultures were done using mouse sarcoma tumor -derived Matrigel. Long-term preservation of cultivated tissues was evaluated against typical immunohistochemical biomarkers for each tissue type: skin tissues for cytokeratins 5/6, E-cadherin and vimentin for sustained tissue structures, and brain neoplasia for Olig2, S100, Nestin, NOTCH1, MAP2 and GFAP for preserved disease profile. Histological analysis from both culture conditions showed that until day 28, all cultivated biopsy types were able to sustain their characteristic protein expressions without signs of necrosis. We here conclude a novel tissue culture model in xeno-free 3D scaffolding, that can enable long-term sample storage in vitro, studies of human tumor tissues and their non-neoplastic microenvironment, and innovations in personalized medicine research.

cell biology↗

The DNA methylation landscape of glioblastoma disease progression shows extensive heterogeneity in time and space

Glioblastoma is characterized by widespread genetic and transcriptional heterogeneity, yet little is known about the role of the epigenome in glioblastoma disease progression. Here, we present genome-scale maps of the DNA methylation dynamics in matched primary and recurring glioblastoma tumors, based on a national population registry and a comprehensively annotated clinical cohort. We demonstrate the feasibility of DNA methylation mapping in a large set of routinely collected formalin-fixed paraffin-embedded (FFPE) samples, and we validate bisulfite sequencing as a multi-purpose assay that allowed us to infer a range of different genetic, epigenetic, and transcriptional tumor characteristics. Based on these data, we identified characteristic differences between primary and recurring tumors, links between DNA methylation and the tumor microenvironment, and an association of epigenetic tumor heterogeneity with patient survival. In summary, this study provides a resource for dissecting DNA methylation heterogeneity in genetically diverse and heterogeneous tumors, and it demonstrates the feasibility of integrating epigenomics, radiology, and digital pathology in a representative national cohort, leveraging samples and data collected as part of routine clinical practice.

cancer biology↗