Stem Cells in Traumatic Brain Injury

2018

Traumatic brain injury (TBI) has been recognized as one of the major public health issues that leads to devastating neurological disability. As a consequence of primary and secondary injury phases, neuronal loss following brain trauma leads to pathophysiological alterations on the molecular and cellular levels that severely impact the neu-ropsycho-behavioral and motor outcomes. Thus, to mitigate the neuropathological sequelae post-TBI such as cerebral edema, inflammation and neural degeneration, several neurotherapeutic options have been investigated including drug intervention, stem cell use and combinational therapies. These treatments aim to ameliorate cellular degen-eration, motor decline, cognitive and behavioral deficits. Recently, the use of neural stem cells (NSCs) coupled with selective drug therapy has emerged as an alternative treatment option for neural regeneration and behavioral rehabilitation post-neural injury. Given their neuroprotective abilities, NSC-based neurotherapy has been widely investigated and well-reported in numerous disease models, notably in trauma studies. In this review, we will elaborate on current updates in cell replacement therapy in the area of neurotrauma. In addition, we will discuss novel combination drug therapy treatments that have been investigated in conjunction with stem cells to overcome the limitations associated with stem cell transplantation. Understanding the regenerative capacities of stem cell and drug combination therapy will help improve functional recovery and brain repair post-TBI.

Behavioural Brain Research, 2016

This review covers existing treatment options and recent advancements in TBI therapy, with a focus on the potential application of these strategies as a solution to improve the functional outcomes of TBI  Complex pathophysiology and molecular mechanisms of TBI are reviewed.  Currently available treatments for TBI including the recent approaches in the field of stem cell therapy as an optimal solution to treat TBI are reviewed.  Therapy using endogenous stem cells were reviewed, followed by therapies utilizing exogenous stem cells from embryonic, induced pluripotent, mesenchymal, and neural origin.  Combination therapy is also discussed as an emergent novel approach to treat TBI. Two approaches are highlighted, an approach concerning growth factors and another using ROCK inhibitors. These approaches are highlighted with regard to their benefits in minimizing the outcomes of TBI.  Finally, we focus on the consequent improvements in motor and cognitive functions after stem cell therapy.

Folia Neuropathologica

Traumatic brain injury (TBI) is a global health issue which causes millions of deaths and disabilities every year. The survivors of TBI may suffer from sensorimotor dysfunction, memory and cognitive disturbances, hearing and vision deficits, and various psychological problems. The primary insult may damage neurons, cerebral vessels and the blood-brain barrier, causing reactive astrogliosis and immune response with further damaging consequences. TBI lacks effective therapy. The currently available clinical treatment options include hyperbaric oxygenation, brain stimulation and rehabilitation. In recent years, the research on stem cell treatment of TBI has received extensive attention. Various types of stem cells, such as four types of mesenchymal stem cells, neural stem cells and olfactory ensheathing cells have been tried to treat TBI in clinical trials and preclinical models. This article reviews the research of autologous and non-autologous multipotent stem and progenitor cells for the treatment of TBI in both clinical and preclinical settings.

Frontiers in neurology, 2018

Traumatic brain injury (TBI) is a major cause of death worldwide. Depending on the severity of the injury, TBI can reflect a broad range of consequences such as speech impairment, memory disturbances, and premature death. In this study, embryonic neural stem cells (ENSC) were isolated from E14 mouse embryos and cultured to produce neurospheres which were induced to generate differentiated cells (DC). As a cell replacement treatment option, we aimed to transplant ENSC or DC into the adult injured C57BL/6 mouse cortex controlled cortical impact (CCI) model, 7 days post-trauma, in comparison to saline injection (control). The effect of grafted cells on neuroinflammation and neurogenesis was investigated at 1 and 4 weeks post-transplantation. Results showed that microglia were activated following mild CCI, but not enhanced after engraftment of ENSC or DC. Indeed, ipsilateral lesioned somatosensory area expressed high levels of Iba-1+ microglia within the different groups after 1 and 4 w...

Arquivos de Neuro-Psiquiatria, 2014

Central nervous system (CNS) restoration is an important clinical challenge and stem cell transplantation has been considered a promising therapeutic option for many neurological diseases. Objective : The present review aims to briefly describe stem cell biology, as well as to outline the clinical application of stem cells in the treatment of diseases of the CNS. Method : Literature review of animal and human clinical experimental trials, using the following key words: “stem cell”, “neurogenesis”, “Parkinson”, “Huntington”, “amyotrophic lateral sclerosis”, “traumatic brain injury”, “spinal cord injury”, “ischemic stroke”, and “demyelinating diseases”. Conclusion : Major recent advances in stem cell research have brought us several steps closer to their effective clinical application, which aims to develop efficient ways of regenerating the damaged CNS.

2016

Central nervous system (CNS) restoration is an important clinical challenge and stem cell transplantation has been considered a promising therapeutic option for many neurological diseases. Objective: The present review aims to briefly describe stem cell biology, as well as to outline the clinical application of stem cells in the treatment of diseases of the CNS. Method: Literature review of animal and human clinical experimental trials, using the following key words: “stem cell”, “neurogenesis”, “Parkinson”, “Huntington”, “amyotrophic lateral sclerosis”, “traumatic brain injury”, “spinal cord injury”, “ischemic stroke”, and “demyelinating diseases”. Conclusion: Major recent advances in stem cell research have brought us several steps closer to their effective clinical application, which aims to develop efficient ways of regenerating the damaged CNS.

British Medical Bulletin, 2012

Polymers, 2018

The use of advanced biomaterials as a structural and functional support for stem cells-based therapeutic implants has boosted the development of tissue engineering applications in multiple clinical fields. In relation to neurological disorders, we are still far from the clinical reality of restoring normal brain function in neurodegenerative diseases and cerebrovascular disorders. Hydrogel polymers show unique mechanical stiffness properties in the range of living soft tissues such as nervous tissue. Furthermore, the use of these polymers drastically enhances the engraftment of stem cells as well as their capacity to produce and deliver neuroprotective and neuroregenerative factors in the host tissue. Along this article, we review past and current trends in experimental and translational research to understand the opportunities, benefits, and types of tentative hydrogel-based applications for the treatment of cerebral disorders. Although the use of hydrogels for brain disorders has been restricted to the experimental area, the current level of knowledge anticipates an intense development of this field to reach clinics in forthcoming years.

In vitro models, 2022

Stimulating brain tissue regeneration is a major challenge after central nervous system (CNS) injury, such as those observed from trauma or cerebrovascular accidents. Full regeneration is difficult even when a neurogenesis-associated repair response may occur. Currently, there are no effective treatments to stimulate brain tissue regeneration. However, biomaterial scaffolds are showing promising results, where hydrogels are the materials of choice to develop these supportive scaffolds for cell carriers. Their combination with growth factors, such as brain-derived neurotrophic factor (BDNF), basic fibroblast growth factor (bFGF), or vascular endothelial growth factor (VEGF), together with other cell therapy strategies allows the prevention of further neuronal death and can potentially lead to the direct stimulation of neurogenesis and vascularisation at the injured site. Imaging of the injured site is particularly critical to study the reestablishment of neural cell functionality aft...

Stem cells international, 2017

Traumatic brain injury (TBI) is a complex condition that presents with a wide spectrum of clinical symptoms caused by an initial insult to the brain through an external mechanical force to the skull. In the United States alone, TBI accounts for more than 50,000 deaths per year and is one of the leading causes of mortality among young adults in the developed world. Pathophysiology of TBI is complex and consists of acute and delayed injury. In the acute phase, brain tissue destroyed upon impact includes neurons, glia, and endothelial cells, the latter of which makes up the blood-brain barrier. In the delayed phase, "toxins" released from damaged cells set off cascades in neighboring cells eventually leading to exacerbation of primary injury. As researches further explore pathophysiology and molecular mechanisms underlying this debilitating condition, numerous potential therapeutic strategies, especially those involving stem cells, are emerging to improve recovery and possibl...