Sex hormones and their receptors in osteoarthritis: current research progress.

Spinal cord injury (SCI) causes persistent neurological disability and societal burden, with few therapies that meaningfully restore function [,,]. Transplantation of neural precursor cells (NPCs) remains attractive because NPCs generate neurons and glia, modulate the lesion milieu, and can integrate into host circuits [,,,]. However, post-transplant survival and lineage maturation are modest in vivo, limiting functional benefit [,,]. The initial mechanical trauma in SCI is followed by a protracted secondary-injury cascade—ischemia, glutamate excitotoxicity, oxidative stress, and sustained neuroinflammation—that propagates tissue loss well beyond the original epicenter []. Over the following days to weeks, reactive astrocytes, microglia, and infiltrating immune cells demarcate the lesion and deposit a chondroitin-sulfate-proteoglycan-rich matrix, forming a glial scar that, although it initially contains the damage, matures into a durable barrier to axonal growth and endogenous repair [,]. This same cytotoxic, inflammatory, and scar-forming milieu is inhospitable to exogenous cells, contributing to the poor graft survival, limited integration, and skewed differentiation that have tempered the clinical translation of stem- and precursor-cell therapies for SCI [,]. These obstacles have shifted emphasis toward combinatorial approaches that pair cell transplantation with agents capable of remodeling the lesion into a more regeneration-permissive environment. Sonic hedgehog (Shh) regulates ventral cord differentiation and progenitor dynamics via PTCH-SMO-GLI signaling [,,,]. Beyond development, Shh can modulate astrogliosis and inflammatory tone and has been reviewed as a target for SCI repair across neuroprotection, plasticity, and immune regulation [,,,]. In rodent SCI, pump-based Shh in the subacute phase reduces neuroinflammation and supports recovery [,,].