Regenerating the Injured Spinal Cord at the Chronic Phase by Engineered iPSCs-Derived 3D Neuronal Networks.
Lior WertheimReuven EdriYona GoldshmitTomer KaganNadav NoorAngela RubanAssaf ShapiraIrit Gat-ViksYaniv AssafTal DvirPublished in: Advanced science (Weinheim, Baden-Wurttemberg, Germany) (2022)
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.
Keyphrases
- spinal cord
- cell therapy
- stem cells
- endothelial cells
- induced pluripotent stem cells
- spinal cord injury
- neuropathic pain
- induced apoptosis
- primary care
- mesenchymal stem cells
- single cell
- drug induced
- gene expression
- tissue engineering
- subarachnoid hemorrhage
- cell proliferation
- mass spectrometry
- diabetic rats
- endoplasmic reticulum stress
- cell death
- soft tissue
- network analysis
- hematopoietic stem cell