Introduction: There are no neuroprotective and neuroregenerative treatments available for Traumatic Brain Injury (TBI). Clinical trials investigating potential treatments such as therapeutic hypothermia and progesterone have failed. Pre-clinical studies indicate there may be a role of stem-cells in promoting neuroprotection/neuroregeneration in-vivo in animal models of TBI. We aim to provide a pre-clinical literature review into stem-cells as a potential therapeutic option in TBI-animal models.
Methods: Using the terms “traumatic brain injury”, “stem-cell”, “preclinical”, and “animal studies”, a literature search was conducted on Pubmed and Google Scholar. Studies were included if there was an in-vivo animal model of TBI with either intravenous or intra-cortical stem-cell transplantation, along-with a control group, and investigated either motor or behavioral outcomes, or a combination.
Results: Twenty-seven studies (n=1184 animals) satisfied the criteria (Table-1). 774/1184 (65.4%) animals were investigated for outcomes. 17 studies harvested stem-cells from human-source, whereas 10 harvested stem-cells from animal-source. Bone-marrow stromal-cells (BMSC) were used in 17 studies, neural stem-cells (NSC) in 7, and miscellaneous in 3. 450/774 (58.1%) animals received any stem-cell transplantation, whereas 324 were controls. Of animals receiving stem-cell transplantation (450), 339 (75.3%) showed significantly better outcomes relative to control animals in each individual study, with exception of one study. Amongst transplanted animals, functional outcomes did not differ significantly when grouped by stem-cell type (p=0.553), transplantation route (p=0.054), and source (p=0.784) (Figure 1). Animals were followed-up until 1 week (n=5 studies), 2 weeks (n=10), 4 weeks (n=5), or >4-weeks (n=7).
Conclusions: This pre-clinical data demonstrates that stem-cell transplantation may have treatment potential in TBI as shown by improvement in functional outcome in as many as three-quarters of all animals that were treated with stem-cells. This data provides a foundation for the design of clinical translational studies.
Patient Care: There are currently no neuroprotective and neuroregenerative therapies available for improving outcomes after traumatic brain injury. Clinical trials investigating such therapies have failed to show benefit. Stem cell treatments have been shown to have some role in improving functional outcomes in animal models of TBI. These preclinical studies are important to be familiar with for clinicians, as these would provide the foundation of design of clinical translational studies. It can only be hoped that research into stem cells may provide a new frontier of treatment for a condition as disabling as traumatic brain injury.
Learning Objectives: By conclusion of this session, participants should be able to:
1. Recognize that there are currently no neuroprotective and neuroregenerative treatments available for traumatic brain injury
2. Discuss, in small groups, the available evidence on the impact of stem cell therapy on outcomes in pre-clinical animal models of TBI
3. Understand that Stem cell therapy may be the next investigative frontier for patients with TBI and that this literature review provides a foundation for clinical translational studies