Nanoengineered 3D culture substrate enables superior persistence and polyclonal engraftment of genetically engineered hematopoietic stem cells.

ABSTRACT: Ex vivo culture of hematopoietic stem and progenitor cells (HSPCs) is required for gene therapy applications but inadvertently triggers detrimental cellular responses, potentially threatening clinical success. In this study, we employ nichoids, biocompatible 3D culture substrates with cell-scale resolution, to provide HSPCs with mechanical support during ex vivo manipulation. This innovative 3D system improves HSPC multi-lineage differentiation and engraftment capacity by leveraging mechanobiological control over nuclear morphology, cytoskeleton organization, metabolism, and DNA integrity. Notably, 3D culture enables efficient genetic engineering across multiple platforms, including long-range gene editing, base- and prime-editing, and lentiviral-mediated gene addition. Moreover, this scaf

SUBMITTER: Midena F 

PROVIDER: S-EPMC12904609 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature