Protective Role of the Immune System in Spinal Cord Injury: Immunomodulation with Altered Peptide Ligands

Spinal cord injury (SCI) is a phenomenon characterized by damage to the spinal cord and nerve roots, resulting in loss of physiological activity below the lesion. Injury to the spinal cord activates a cascade of cellular and molecular reactions in which the immune system plays an essential role, as there is an uncontrolled immune response that endows further damage to neural tissue. However, the activity of immune system at the site of injury can be modified in order to obtain a neuroprotective environment and promote SCI recovery. This strategy has been designed under the light of the innovative concept “protective autoimmunity” (PA) and can be stimulated with the use of altered peptide ligands (APL). Adequate immunomodulation with APL can be obtained with the peptide A91, which is a safe synthetic peptide derived from the myelin basic protein (MBP) that has proven to be effective in preclinical research. Immunization with A91 is carried out with the objective of preventing further damage and promoting neuroprotection. This peptide has direct influence over SCI secondary mechanisms such as inflammation, lipid peroxidation, and apoptosis. Preclinical results suggest that immunization with A91 could be an effective treatment in the clinical field, providing a better quality of life to SCI patients

Amnion-derived stem cell transplantation: A novel treatment for neurological disorders

In this review, we evaluated the literature reporting the use of amniotic stem cells (ASCs) in regenerative medicine for the treatment of neurological disorders. There is an increasing amount of evidence that indicates the exacerbation of the primary injury by inflammation in neurological disorders characterized by rampant inflammation, thereby increasing damage to the central nervous system (CNS). To address this, we focus on the amnion cells′ anti-inflammatory properties, which make their transplantation a promising treatment for these disorders. In addition, we offered insights into new applications of the ASC in the fields of regenerative medicine and tissue engineering

Uso de péptidos neurales modificados como tratamiento de una lesión en la médula espinal: una vision general

La lesión de la médula espinal ( lme ) es un fenómeno que daña al sistema nervioso central ( snc ), y produce la pérdida de la actividad fisiológica por debajo del sitio de la lesión. Actualmente no existe algún tratamiento efectivo para la lme en el campo clínico. El papel del sistema inmune a través de la autorreactividad protectora ( ap ) —un fenómeno fisiológico desa - rrollado después de la lme — puede ser de gran importancia para inducir neuroprotección. La ap puede estimularse con el uso de péptidos neurales modificados ( pnm ) procedentes de componentes neurales como la proteína básica de la mielina. El presente artículo pretende dar una visión general de esta estrategia terapéutica innovadora que ofrece efectos bené - ficos y un futuro muy alentador. Se revisará el fundamento, los mecanismos y los hallazgos preclínicos más importantes utilizando el pnm a 91. Finalmente, se comentarán los obstáculos a vencer para su aplicación clínica

Regenerative medicine for central nervous system disorders: Role of therapeutic molecules in stem cell therapy

The efficacy of stem cell therapy is greatly influenced by their secretory properties. Evidence suggests that there is a high concentration of growth factors such as brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), and glial cell line-derived neurotrophic factor (GDNF) after stem cell transplantation. Also, the presence of therapeutic molecules and cytokines such as stem cell factor (SCF), stromal cell-derived factor-1α (SDF-1α), RNAs, nuclear enriched abundant transcript 1 (NEAT1), and metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is consistent throughout several studies. Apart from modulating the homeostasis of the surrounding tissues, these factors have pleiotropic properties over the host tissue, among which are angiogenic, anti-inflammatory, antiapoptotic, and neurogenic effects. In the present manuscript, we discuss the different secretion factors and their beneficial activity after stem cell transplantation. Recent developments in emerging technologies for coadjunctive therapies that may aid in stem cell transplantation into the central nervous system, such as cell encapsulation, molecular Trojan horses, and viral vectors, are also presented in this article

Behavior of glioblastoma brain tumor stem cells following a suborbital rocket flight: reaching the “edge” of outer space

Abstract The emerging arena of space exploration has created opportunities to study cancer cell biology in the environments of microgravity and hypergravity. Studying cellular behavior in altered gravity conditions has allowed researchers to make observations of cell function that would otherwise remain unnoticed. The patient-derived QNS108 brain tumor initiating cell line (BTIC), isolated from glioblastoma (GBM) tissue, was launched on a suborbital, parabolic rocket flight conducted by EXOS Aerospace Systems & Technologies. All biologicals and appropriate ground controls were secured post-launch and transported back to our research facility. Cells from the rocket-flight and ground-based controls were isolated from the culture containers and expanded on adherent flasks for two weeks. In vitro migration, proliferation, and stemness assays were performed. Following cell expansion, male nude mice were intracranially injected with either ground-control (GC) or rocket-flight (RF) exposed cells to assess tumorigenic capacity (n = 5 per group). Patient-derived QNS108 BTICs exposed to RF displayed more aggressive tumor growth than the GC cells in vitro and in vivo. RF cells showed significantly higher migration (p < 0.0000) and stemness profiles (p < 0.01) when compared to GC cells. Further, RF cells, when implanted in vivo in the brain of rodents had larger tumor-associated cystic growth areas (p = 0.00029) and decreased survival (p = 0.0172) as compared to those animals that had GC cells implanted