Traumatic brain injury Stem Cell Treatment(TBI)

Traumatic brain injury Stem Cell Treatment(TBI):

Traumatic brain injury (TBI) is mostly caused by an external physical impact producing an altered state of consciousness resulting in impairment of physical functions or cognitive abilities It is one of the leading causes of morbidity and mortality in the world. The damage to the brain could be either focal or diffused depending on the event causing TBI. The outcome consists of two stages (a) primary insult, which occurs at the time of impact (b) Secondary insult, which is a cascade of events after the primary insult with delayed clinical presentation. Alterations in cerebral blood flow and oxygenation, edema, excitotoxicity, cell death, disruption of the blood brain barrier, and generalized atrophy is commonly observed in TBI. The damage to the brain could result in temporary or permanent behavioral and/or emotional disturbances leading to functional disability. Very few treatment alternatives are currently available to treat TBI. Pharmacological and surgical intervention along with rehabilitation are used for the management of the symptoms. 

Unmet medical needs 

In chronic TBI, the life expectancy of the affected is normal, but there is high prevalence of the residual disability arising from the injury. These include hemiparesis, spasticity, cognitive, emotional and behavioral issues, etc. The available pharmacological modalities manage these disabilities, but their effect wears off gradually. The rehabilitation resources are inadequate for the increasing number of survivors of TBI. There is diffuse white matter damage which cannot be addressed by current medical treatments. Also, the gliotic areas in the brain cannot be reversed. Stem cell therapy in TBI Due to the brain’s limited capacity to regenerate the damaged neaurons, the intervention should aim at halting the degeneration and replacing the lost and damaged neurons. In past few years, cell therapy has gained attention as a prospective therapeutic options for neurological disorders. Stem cells migrate towards the damaged areas of the brain and initiate the repair process. They promote angiogenesis, axonal remodeling, neurogenesis and synaptogenesis, which may help reverse the pathology of TBI. These cells differentiate into various cells including neural cells, oligodendrocytes, etc. In TBI, there is loss of myelin which disrupts the signal transduction and damages the axons. The oligodendrocytes help in remyelination of the damaged axons and repair the disrupted neural connections. Bone marrow cells also produce various growth factors and neurotrophic factors such as brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and hepatocyte growth factor (HGF), which stimulate the endogenous neuroprotection and repair.  

Animal studies  

Various experiments on animal models have been carried out to test the safety and feasbility of different types of cells. Reiss et al, transplanted embryonic cells in experimental rats and recorded dramatic improvements. But, over the period of observation they also recorded tumor formation in the rats, raising serious safety concerns about the use of these cells. Series of experiments were conducted to study the neural stem cells in TBI which reported improved neurological functions in the injected rat models via various mechanism. Bone marrow stem cells were also found to be efficacious. In rat models, these cells modulated the inflammationassociated immune cells and cytokines in TBI-induced cerebral inflammatory responses. Recently umbilical cord cells have also been tested in rats. In an experimental study, rats were injected with brain-derived neurotrophic factor (BDNF) gene-modified umbilical cord mesenchymal stem cell (UCMSC). These cells survived and migrated to the cerebral tissues. They led to dramatic improvements in behavior and other neurological functions. 

Human Studies  

Traumatic brain injury Stem Cell Treatment(TBI) is still in an experimental stage. Not many clinical trials have been conducted on human subjects. Wang et al published the results of his study conducted on patients with sequelae of TBI. He administered 40 patients with umbilical cord mesenchymal stem cells. They observed improved neurological functions and self care in these patients as compared to the controls.