Translational stem cell therapy for neurodegeneration and CNS trauma: a focused review

Abstract

Central nervous system (CNS) disorders, including spinal cord injury (SCI) and traumatic brain injury (TBI), often result in severe and irreversible functional impairments due to complex pathophysiological processes such as neuroinflammation, axonal damage, and neuronal cell death. Conventional treatment strategies have shown limited efficacy in restoring neurological function. Stem cell therapy has emerged as a promising avenue for CNS repair, offering potential benefits such as neuronal regeneration, modulation of immune responses, and secretion of neurotrophic factors. Various stem cell types, including neural stem cells (NSCs), mesenchymal stem cells (MSCs), and induced pluripotent stem cells (iPSCs), have demonstrated therapeutic potential in the preclinical and early clinical studies for conditions such as TBI, SCI, stroke, Parkinson's disease, and multiple sclerosis. Despite significant progress, challenges such as cell delivery optimization, risk of tumorigenesis, immune compatibility, and ethical concerns must be addressed to enable broader clinical application. This review highlights the recent advances in stem cell-based therapies for CNS disorders, discusses the mechanisms underlying their therapeutic effects, and outlines future directions for research and clinical translation.Graphical abstractStem cell therapies show therapeutic effects in central nervous system disorders through multiple complementary mechanisms. Following transplantation, stem cells and their secreted factors can promote neuronal and glial replacement, modulate neuroinflammation, reduce apoptosis and oxidative stress, enhance angiogenesis and tissue repair, and restore synaptic plasticity and neural circuit function. The relative contribution of each mechanism depends on the disease context and the specific cellular product used. Collectively, these actions aim to preserve neural tissue integrity, improve functional recovery, and modify disease progression in neurodegenerative diseases and central nervous system trauma