Regenerating the Injured Spinal Cord at the Chronic Phase by Engineered iPSCs-Derived 3D Neuronal Networks

Lior Wertheim, Reuven Edri, Yona Goldshmit, Tomer Kagan, Nadav Noor, Angela Ruban, Assaf Shapira, Irit Gat-Viks, Yaniv Assaf, Tal Dvir

Research output: Contribution to journalArticlepeer-review

Abstract

Cell therapy using induced pluripotent stem cell-derived neurons is considered a promising approach to regenerate the injured spinal cord (SC). However, the scar formed at the chronic phase is not a permissive microenvironment for cell or biomaterial engraftment or for tissue assembly. Engineering of a functional human neuronal network is now reported by mimicking the embryonic development of the SC in a 3D dynamic biomaterial-based microenvironment. Throughout the in vitro cultivation stage, the system's components have a synergistic effect, providing appropriate cues for SC neurogenesis. While the initial biomaterial supported efficient cell differentiation in 3D, the cells remodeled it to provide an inductive microenvironment for the assembly of functional SC implants. The engineered tissues are characterized for morphology and function, and their therapeutic potential is investigated, revealing improved structural and functional outcomes after acute and chronic SC injuries. Such technology is envisioned to be translated to the clinic to rewire human injured SC.

Original languageEnglish
Article number2105694
JournalAdvanced Science
Volume9
Issue number11
DOIs
StatePublished - 14 Apr 2022

Keywords

  • 3D neuronal network
  • chronic phase injury
  • differentiation
  • induced pluripotent stem cells
  • spinal cord injury
  • tissue engineering
  • tissue implants

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