Stem Cell Therapies for Functional Recovery After Spinal Cord Injury: Mechanisms, Challenges, and Applications

Context: Spinal cord injury (SCI), a debilitating and catastrophic condition, leads to sensory motor impairments, paralysis, and high mortality. It consists of initial physical insult and secondary injury. Despite much research on SCI treatment, it is still one of the incurable damages because of its complex pathophysiology and limited neuronal regeneration ability. In recent years, stem cell therapy has been a promising and exciting strategy for SCI treatment. Evidence Acquisition: In this review, the articles published in PubMed, Google Scholar, Science Direct, and Scopus from 2000 to 2022 were collected using keywords such as spinal cord injury, stem cell therapy, neuroprotection, neuroregeneration, neurotrophic factors, anti-inflammatory cytokines, and neural cell death. The articles whose full texts were available and met the inclusion criteria were examined. According to the inclusion criteria, 30 articles were analyzed. Results: Stem cell therapy can promote neuroplasticity and neuroregeneration in the damaged spinal cord. Grafted cells can reconstruct nerves and create new circuits after SCI. Stem cell transplantation can also replace lost oligodendrocytes, thus promoting axon remyelination. Many neurotrophic factors and anti-inflammatory cytokines are secreted by transplanted stem cells to decrease secondary injury and neural cell death, thus inhibiting the glial scar formation after SCI. Stem cells also have antioxidant, anti-inflammatory, immunomodulatory, and anti-apoptotic effects. Grafted stem cells can block microglial activation and astrocyte reactivity and enhance revascularization. Conclusions: Stem cells isolated from different tissues can be promising candidates and attractive options for treating the injured spinal cord. Despite remarkable progress in animal studies, cell transplantation's clinical efficacy and adequacy for SCI remain limited and dubitable. Many essential challenges must be considered in translation to the clinic. It is hoped that the invention of new methods and the anti-inflammatory, anti-apoptotic, antioxidant, and neuronal repair properties of stem cells can effectively improve the sensorimotor function of patients with SCI.