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Bioresorbable nanopatterned scaffolds functionalized with polydopamine (PDA) and graphene oxide (GO) have been shown to promote the differentiation of murine neural stem cells (mNSCs) toward neural and glial lineages. Herein, we aim to evaluate the compatibility of these scaffolds for the culture and differentiation of both human embryonic (hESCs) and induced pluripotent (hiPSCs) stem cells. Our results indicate that PDA and GO scaffolds support the topographic alignment of hESCs and hiPSCs cultures, while preserving their pluripotency characteristics. Upon differentiation, PDA and GO scaffolds guide cell specification toward the neuroectoderm germ layer and the neural crest. This promotes enhanced differentiation into both neural and supportive glial cells of the central nervous system (CNS), as well as Schwann cells of the peripheral nervous system (PNS). Moreover, nanopatterned scaffolds also support the differentiation of hESCs and hiPSCs toward endothelial precursors. These findings establish a novel culture platform that enables combined differentiation pathways, potentially relevant for applications in personalized medicine and regenerative cell therapy.

Hsp90 is a molecular chaperone that is often overexpressed across multiple cancer types and has a potential value as a prognostic marker as well as a therapeutic target. Given the high interest in Hsp90 therapies, positron emission tomography or PET imaging of Hsp90 can be a valuable tool for patient selection. The limitations of the previously developed Hsp90 tracers prompted us to evaluate the recently developed brain-permeable [ 11 C]HSP990 PET probe to advance the development of Hsp90-targeted therapeutics. Given the brain accumulation of [ 11 C]HSP990 probe, application for glioblastoma imaging of this tracer is of particular interest. In vitro [ 11 C]HSP990 binding was assessed in breast cancer and glioma cell lines including patient-derived cells using Hsp90 inhibitors and RNA interference knockdown of Hsp90 isoforms. Saturation binding studies were conducted on these cells and tumour tissue homogenates, and autoradiography was performed on tissue sections. Ex vivo biodistribution and in vivo dynamic µPET/CT studies were performed in healthy mice and tumour-bearing mice, including immunocompromised subcutaneous human U87 and MDA-MB-231models and immunocompetent intracranial murine NS/CT-2A models at baseline and following a pre-treatment with Hsp90 inhibitors. High Hsp90-specific tracer uptake was observed in breast cancer and glioma cells, with Hsp90β inhibition resulting in the most substantial reduction in uptake. In vivo uptake was high in U87 tumours but low in MDA-MB-231, presumably due to the differences in Hsp90 expression in tumour tissue versus cultured cells. Differences in maximum binding capacity or B max across cell and tissue types support this hypothesis, especially given that the affinity measured as dissociation constant K d remained similar across all tissue types. Despite high NS/CT-2A tumour uptake in vitro, no contrast between the healthy brain tissue and the NS/CT-2A glioma was observed in vivo due to the high uptake by the healthy brain. [ 11 C]HSP990 is a promising tracer for identifying Hsp90-overexpressing tumours and may hold potential for patient stratification, prognosis, and therapy monitoring of novel Hsp90 therapeutics. High healthy brain uptake of this tracer precluded the differentiation of the tumour in the intracranial NS/CT-2A tumour model, therefore [ 11 C]HSP990 might not be a suitable tracer for the glioblastoma imaging. Tracer with a longer half-life might be needed to compare the washout of the tracer from the brain and the tumour tissue over several hours to identify a suitable imaging window. The online version contains supplementary material available at 10.1186/s41181-025-00386-z.

Glioblastoma (GBM) remains a formidable challenge in clinical settings due to limited treatments available. The surface protein CD133 marks glioblastoma stem cells (GSCs), cells capable of overcoming therapeutic pressures and correlate with more aggressiveness tumor phenotypes. In this study, we employed a CRISPR-Cas9 functional screen to deconvolute CD133 dynamics in tumors. This led us to establish that SOX2 is a key player in controlling the PROM1 gene, which in turn influences how cells react to stress factors, including those induced by chemoradiation treatment. The discoveries in this study shed light on the complex web of mechanisms that control the survival and resistance of GSCs, offering promising new avenues for targeting and potentially overcoming therapy resistance.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-20183-7.