Mesenchymal stromal cells as a choice for spinal cord injury treatment

Abstract

Spinal cord injury (SCI) is a serious clinical problem that affects approximately 17,500 new patients per year in the United States. The main causes of SCI are vehicle collisions, falls, violence (mainly gunshot wounds), and sports/recreational activities. The final severity of the damage results from primary and secondary mechanisms that begin at the time of injury and last for months after trauma. To reduce the extent of damage, several treatments have been proposed. This review summarizes results from several studies that have pointed to cell therapy as the main form of neuroregenerative treatment. Mesenchymal stromal cells (MSCs) are important candidates for tissue regeneration due to the release of bioactive factors, as well as antiapoptotic effects, scar inhibitors, and angiogenic effects. Studies have shown that MSCs act in various ways on injured tissue, such as immunomodulation of the inflamed environment, release of bioactive factors, restoration of axon myelin, prevention of neuronal apoptosis, and neuroregeneration. Current research using MSCs aims to prevent secondary injury, promote regeneration, and replace destroyed spinal cord tissue. This review presents information about the damage from primary and secondary events after SCI, treatments usually used, and preclinical and clinical results aiming at the cell therapy using MSCs as a tissue regeneration strategy.

Application of mesenchymal stem cells for treating spinal cord injury in dogs: Mechanisms and their therapeutic efficacy

“…Transplanted MSCs secrete a broad range of neurotrophic factors at the SCI lesion site in response to the surrounding environment (Wright et al 2012, Teixeira et al 2013, Hofer et al 2016. These neurotrophic factors influence neighbouring cells and regulates multiple biological processes such as preventing neuronal apoptosis, inflammation and glial scar, vascular angiogenesis, axonal myelination, and neuroregeneration, which are required for wound healing of SCI (Fracaro et al 2020).…”

“…The mechanical damage to the spinal cord causes immediate cell death and vascular injury with disruption of the blood-brain barrier at the lesion site. It is followed by immediate extravasation of inflammatory cells to the injury site (Fracaro et al 2020). Matrix metalloproteinases, other proteolytic and oxidative enzymes, and proinflammatory cytokines that are produced by infiltrating neutrophils and macrophages, along with resident microglia, induce a reactive process of secondary cell death in the tissue periphery to the lesion site due to DNA damage, protein oxidation, and mitochondrial malfunction (Kjell and Olson 2016, Ahuja et al 2017.…”

“…Matrix metalloproteinases, other proteolytic and oxidative enzymes, and proinflammatory cytokines that are produced by infiltrating neutrophils and macrophages, along with resident microglia, induce a reactive process of secondary cell death in the tissue periphery to the lesion site due to DNA damage, protein oxidation, and mitochondrial malfunction (Kjell and Olson 2016, Ahuja et al 2017. The secondary damage continues in the days and years after SCI, which may lead to an increase in cavity and cyst formation at the centre of the lesion site, further exacerbating neurological dysfunction (Fracaro et al 2020). Some pieces of evidence suggested extensive migration of macrophages and astrocytes to the lesion site in chronic cases (Wright et al 2012).…”

“…Astrocytes secrete a wide range of cytotoxic extracellular matrices and form a physical barrier at the periphery of the SCI lesion site, that walls off or encapsulates the lesion from that of healthy tissues (Zweckberger et al 2016). This wall is called a glial scar, which contributes to an environment that is inhibitory to axonal regeneration (Fracaro et al 2020). Hence, SCI treatment should aim at the prevention of secondary tissue damage followed by restoration of the neuronal circuit, and re-establishment of a damaged axon and synaptic connection.…”

Spinal cord regeneration: A brief overview of the present scenario and a sneak peek into the future

“…Cell‐based therapy came out as an advancement over nerve grafts due to their injectable and genetically modulating avenue, posing limited damage to spared tissue and enhanced trophic support. [ 77 ] The advent of iPSCs [ 83 ] (induced pluripotent stem cells) and other cell types like MSCs [ 84 ] (mesenchymal stem cells), SCs [ 82 ] (Schwann cells), NSPCs [ 85 ] (neural stem progenitor cells), ESCs (embryonic stem cells), OPCs (oligodendrocyte precursor cells), OECs [ 86 ] (olfactory ensheathing cells) are reported to assist nerve regeneration, each with its pros and cons. [ 87 ] The two major routes to achieve efficient nerve regeneration can be augmenting native stem cells or injecting/implanting exogenous cells at injured loci to reconstruct lost circuitry.…”