Fostering Regeneration and Functional Improvement in the Injured Spinal Cord by a Novel, Stem Cell Secretome-Based...

Background/Objectives: Spinal cord injury (SCI) causes permanent tissue damage and severely limits functional recovery. We have previously shown that grafted neuroectodermal stem cells (NE-GFP-4C) promote regeneration and motor improvement of the injured cord through the release of specific factors, including Glial cell line-Derived Neurotrophic Factor, interleukin-6, interleukin-10 and Macrophage Inflammatory Protein-1α. Here, we examined whether various delivery routes for these factors could reproduce the effects of stem cell transplantation. Methods: Specifically, these factors were administered either in soluble form via osmotic pumps or via genetically modified fibroblasts. NE-GFP-4C cells served as a positive control, while saline and non-transfected fibroblasts were used as controls. Functional and morphological analyses were conducted to assess the therapeutic impact of the secretome treatment. Results: Both secretome-treated groups and stem-cell-grafted animals showed significantly improved motor outcomes, reduced lesion volumes, enhanced axonal regeneration and decreased astrocytic and microglial activation. Conclusions: These findings suggest that secretome-based delivery of selected factors is a minimally invasive and effective therapeutic strategy that can mimic the regenerative benefits of stem cell transplantation in SCI.