Abstract: Stem cell transplantation has been widely explored as a promising therapeutic approach for spinal cord injury (SCI). However, the lack of functional scaffolds in cell transplantation for SCI treatment leads to low therapeutic efficacy due to poor transplanted cell survival. To address these challenges, we aim to enhance regenerative potential of spinal cord organoids (SCOs) by employing an extracellular matrix (ECM) recapitulating spinal cord-specific microenvironment. Decellularized spinal cord-derived ECM (ScEM) matrix supports 3D culture for development, maturation, and functionality of human induced pluripotent stem cell-derived SCOs comparable to standard organoid culture matrix such as Matrigel. In a rodent SCI model, SCOs transplantation with ScEM hydrogel promotes axonal regeneration with neovascularization in lesions and induces functional restoration of locomotive activity. The combination of tissue-specific decellularized matrix and organoid technology presents a promising strategy for SCI treatment, offering a physiologically relevant three-dimensional environment that supports both organoid development and functional tissue regeneration. Our findings demonstrate the potential of engineered matrix-organoid constructs as an advanced therapeutic platform for spinal cord repair.
Funding Source: 1. The National Research Foundation of Korea (NRF) grant funded by the Ministry of Science and ICT (MSIT) (RS-2021-NR059722) 2. The Bio&Medical Technology Development Program of NRF funded by MSIT (No. RS-2024-00395393)
