3D Gene Engineering: Study Published in Cell Stem Cell. Among the Authors: Raffaella Di Micco

Mon, 12/01/2026

Blood stem cells are the foundation of many successful gene therapies, but their ex vivo manipulation can impair their function, posing a major challenge in preserving their therapeutic potential.

A study recently published in Cell Stem Cell by Raffaella Di Micco’s laboratory (San Raffaele Hospital – Fondazione Telethon – IUSS Pavia Higher University School), with Federico Midena as first author, demonstrates for the first time that integrating a three-dimensional nanoengineered culture system—nichoids—into blood stem cell gene engineering protocols can effectively overcome these limitations.

By providing mechanical cues during ex vivo culture, nichoids preserve genome integrity and cellular functionality, leading to improved multilineage differentiation, increased engraftment, and robust clonal output after transplantation. Importantly, nichoids support efficient gene engineering across multiple clinically relevant platforms, including lentiviral gene addition, long-range gene editing, base editing, and prime editing.

This work establishes 3D culture as an innovative strategy to preserve blood stem cell function during ex vivo manipulation, laying the groundwork for safer and more effective gene therapy and cell therapy approaches.