High-throughput generation of patient-derived cancer stem cells for precision medicine using a microwell-chip platform
Cet article présente une approche méthodologique utilisant une plateforme de culture à micro-puits pour produire à haut débit des microsphères tumorales homogènes à partir d’échantillons limités de cancer du sein (tels que les biopsies par ponction) et faciliter ainsi l’enrichissement en cellules souches cancéreuses ainsi que les tests pharmacologiques personnalisés
Substantial evidence indicates that cancer stem cells (CSCs) drive breast cancer (BRC) initiation, progression, therapy resistance, recurrence and metastasis. Evaluating drug efficacy against patient-derived CSCs can advance precision oncology. However, high-throughput isolation of functional CSCs from small clinical samples remains challenging. Tumoursphere formation, arising from the clonal expansion of a single cancer cell, is a standard in vitro method for CSC assay and enrichment. Here we show a microwell cell-chip culture platform that enables rapid, high-throughput generation of uniform micro-tumourspheres (MTSs) from limited BRC specimens, such as puncture biopsies, facilitating functional CSC enrichment and personalized drug testing within 8 days. Single-cell transcriptomics and limiting dilution tumour initiation assay confirm that MTSs recapitulate CSC functionality, uniformity and heterogeneity. MTSs predicted clinical outcomes in 16 patients with BRC with ~93.8% accuracy, underscoring their translational potential for personalized drug testing. Overall, this platform provides a robust tool for CSC-targeted precision medicine.
Nature Cell Biology , article en libre accès, 2026