Efficacy of Cell-Based Therapies for Traumatic Brain Injuries

Abstract

Traumatic brain injuries (TBIs) are a leading cause of death and disability. Additionally, growing evidence suggests a link between TBI-induced neuroinflammation and neurodegenerative disorders. Treatments for TBI patients are limited, largely focused on rehabilitation therapy, and ultimately, fail to provide long-term neuroprotective or neurorestorative benefits. Because of the prevalence of TBI and lack of viable treatments, new therapies are needed which can promote neurological recovery. Cell-based treatments are a promising avenue because of their potential to provide multiple therapeutic benefits. Cell-based therapies can promote neuroprotection via modulation of inflammation and promote neurorestoration via induction of angiogenesis and neurogenesis. Neural stem/progenitor cell transplantations have been investigated in preclinical TBI models for their ability to directly contribute to neuroregeneration, form neural-like cells, and improve recovery. Mesenchymal stem cells (MSCs) have been investigated in clinical trials through multiple different routes of administration. Intravenous administration of MSCs appears most promising, demonstrating a robust safety profile, correlation with neurological improvements, and reductions in systemic inflammation following TBI. While still preliminary, evidence suggests cell-based therapies may become a viable treatment for TBI based on their ability to promote neuroregeneration and reduce inflammation.

The Effect of Oral Mucosal Mesenchymal Stem Cells on Long-Term Brain Edema and Lesion, Anxiety-Like Behavior, and Cognitive and Motor Outcomes in Experimental Traumatic Brain Injury

“…One of the important and common complications of TBI is also anxiety, which constitutes a signi cant part of the long-term symptoms and complications of TBI [49]. In the present study, post-traumatic anxiety-like behavior was indicated by a decrease in time In line of our results of memory, administration of mouse neural stem / progenitor cells (NSPCs) to mice with TBI could improve memory [51], whereas human NSPC, regardless of its positive e cacy and relieving motor de cits, had no effect on the development of long-term cognitive activity and memory [52]. In a study conducted by Zhou et al (2019), it was shown that MSCs administration ameliorated neurological dysfunction and also memory and learning impairment after TBI [53].…”

Cell-Based Therapies for Traumatic Brain Injury: Therapeutic Treatments and Clinical Trials

“…Preclinical works using NSCs in TBI rat models showed that human NSCs (hNSCs) are capable of surviving engraftment and differentiating into neurons which, in turn, correlate with improvements in neurological recovery [19,60]. Transplanted NSCs can survive in the traumatically injured brain, differentiate into neurons and/or glia, and attenuate motor dysfunction after TBI [61].…”

“…In addition to promoting angiogenesis, BM-MSCs have been shown to ameliorate neuronal dysfunction induced by TBI through promotion of survival and normal growth of surviving neurons. Although neuronal cell death is a major contributor to poor neurologic outcome post-TBI, TBI not only induces cell death in immature granular neurons, it also causes significant dendritic and synaptic degeneration [60]. These observations point to a potential anatomic substrate to explain, in part, the development of post-traumatic memory deficits [135].…”

Recent Advances in Stem Cell Therapies to Address Neuroinflammation, Stem Cell Survival, and the Need for Rehabilitative Therapies to Treat Traumatic Brain Injuries

“…Stem cell-based therapies to treat neuroinflammation in both the acute and chronic phase of TBIs is an approach that has the potential to mitigate secondary cell loss and to promote neurological and functional recovery. Several very recent reviews document the testing, use, and efficacy of pharmacological and stem cell replacement therapies both separately and in combination [ 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 ]. Here, our review serves to highlight some of the most recent research reports in the use of stem cell therapies alone to treat the destructive and chronic neuroinflammatory processes of TBIs.…”

“…Recently published reviews have documented the use and efficacy of stem cell replacement therapies, pharmacological treatments, and combination therapies in the preclinical and basic research settings to treat TBIs [ 8 , 9 , 10 , 11 , 12 , 13 ]. This current review, however, is intended as a perspective focusing on the three therapeutic points mentioned through selected and recent preclinical and basic research in the efficacy of combinatorial stem cell therapies used to treat TBIs.…”