Neural stem cell therapies for spinal cord injury repair: an update on recent preclinical and clinical advances

Abstract

Traumatic spinal cord injury (SCI) is a leading cause of lifelong disabilities. Permanent sensory, motor and autonomic impairments after SCI are substantially attributed to degeneration of spinal cord neurons and axons, and disintegration of neural network. To date, minimal regenerative treatments are available for SCI with an unmet need for new therapies to re-construct the damaged spinal cord neuron-glia network and restore connectivity with the supraspinal pathways. Multipotent neural precursor cells (NPCs) have a unique capacity to generate neurons, oligodendrocytes and astrocytes. Due to this capacity, NPCs have been an attractive cell source for cellular therapies for SCI. Transplantation of NPCs have been extensively tested in preclinical models of SCI in the past two decades. These studies have identified opportunities and challenges associated with NPC therapies. While NPCs have the potential to promote neuroregeneration through various mechanisms, their low long-term survival and integration within the host injured spinal cord limit the functional benefits of NPC-based therapies for SCI. To address this challenge, combinatorial strategies have been developed to optimize the outcomes of NPC therapies by enriching SCI microenvironment, through biomaterials, genetic and pharmacological therapies. In this review, we will provide an in-depth discussion on recent advances in preclinical NPC-based therapies for SCI. We will discuss modes of actions and mechanism by which engrafted NPCs contribute to the repair process and functional recovery. We will also provide an update on current clinical trials and new technologies that have facilitated preparation of medical-grade human NPCs suitable for transplantation in clinical studies.

Editorial: Restoring neural circuits after spinal cord injury

“…To overcome this, strategies such as gene modification, the application of nanomaterials, and the use of ES cells are being considered. These findings underscore the need for further research into factors affecting cell stability in research settings (Hosseini et al, 2024 ).…”

“…Several types of stem cells, including mesenchymal stem cells (MSCs), embryonic stem cells (ESCs), and induced pluripotent stem cells (iPSCs), are being explored for treating SCI. iPSCs, in particular, have the potential to differentiate into neurons, astrocytes, and oligodendrocytes, replacing damaged cells, regulating the spinal cord microenvironment, and promoting axon and myelin sheath regeneration (Hosseini et al, 2024 ). This leads to the reconstruction of neural circuits and facilitates functional recovery.…”

Neural Stem Cell-Derived Small Extracellular Vesicles: key Players in Ischemic Stroke Therapy – A Comprehensive Literature Review

“…NSCs have the multidirectional potential to differentiate into astrocytes, neurons, and oligodendrocytes. Over the past decades, NSCs have served as a valuable therapeutic modality for treating neurological diseases, providing new therapeutic tools and approaches for many refractory neurological diseases, 5 , 6 including ischemic stroke. 7 However, the quick clinical translation of transplanted NSCs has been hindered by concerns over their potential oncogenicity and immunological rejection.…”

Research hotspots and trend analysis of cell transplantation in traumatic spinal cord injury: a bibliometric and visualized analysis

“…Although there have been some bibliometric studies visualizing representative countries and journals in the field of spinal cord injury, there is a lack of discussion on cell transplantation (Kiraz and Demir, 2020). Additionally, there have been some systematic reviews discussing the research progress of neural stem cell therapy in preclinical and clinical settings of spinal cord injury, qualitatively exploring the contribution of neural stem cells to injury repair and functional recovery (Hosseini et al, 2023). However, quantitative analysis of a large body of literature is lacking (Hosseini et al, 2023).…”

“…Additionally, there have been some systematic reviews discussing the research progress of neural stem cell therapy in preclinical and clinical settings of spinal cord injury, qualitatively exploring the contribution of neural stem cells to injury repair and functional recovery (Hosseini et al, 2023). However, quantitative analysis of a large body of literature is lacking (Hosseini et al, 2023). Furthermore, some review articles have analyzed the treatment strategies for spinal cord injury and future research directions, highlighting the need for objective research.…”