Stem cells for therapy in TBI

Abstract

While the pace of traumatic brain injury (TBI) research has accelerated, the treatment options remain limited. Clinical trials are yet to yield successful treatment options, leading to innovative strategies to overcome the severe debilitating consequences of TBI. Stem cells may act as a potential treatment option. They have two key characteristics, the ability of self-renewal and the ability to give rise to daughter cells, which in the case of neural stem cells (NSCs) includes neurons, astrocytes and oligodendrocytes. They respond to the injury environment providing trophic support and have been shown to differentiate and integrate into the host brain. In this review, we introduce the notion of an NSC and describe the two neurogenic niches in the mammalian brain. The literature supporting the activation of an NSC in rodent models of TBI, both in vivo and in vitro, is detailed. This endogenous activation of NSCs may be augmented by exogenous transplantation of NSCs. Delivery of NSCs to assist the host nervous system has become an attractive option, with either fetal or adult NSC. This has resulted in cognitive and functional improvement in rodents, and current animal studies are using human NSCs. While no NSC clinical trials are currently ongoing for TBI, this review touches upon other neurological diseases and discuss how this may move forward into TBI.

DPYSL2 is a novel regulator for neural stem cell differentiation in rats: revealed by Panax notoginseng saponin administration

“…NSC differentiation into neurons, astrocytes, and oligodendrocytes could replace necrotic cells resulting from injuries to promote the structural and functional repair of the brain and spinal cord [50]. However, this self-renewal is not adequate for the recovery of neurological function after brain injury [1,32,47]. NSCs (autologous or grafted) tend to differentiate into gliocytes rather than the neurons which are more valuable in the nervous system's recovery [39,51].…”

One Step at a Time, Stem Cell Therapy for Traumatic Brain Injury Needs Two More Breakthroughs

“…30,[76][77][78] In other TBI and stroke models, cells have been delivered via intravenous (IV), intra-arterial carotid (IAC) or intraparenchymal (IP) injections. However, IV administration causes loss of the majority (~95%) of the cells during lung passage, 55,[79][80][81] whereas IAC injection carries the risk of causing embolic brain infarction and fails to deliver sufficient cells across the vascular wall barrier to the brain parenchyma, which is the major barrier for putative clinical use of this route. Engraftment after IAC injection is also dependent on cell type and adhesion molecule expression.…”

Altered hippocampal neurogenesis during the first 7 days after a fluid percussion traumatic brain injury

“…3,[6][7][8] One of the reasons that stem cell therapy is such an appealing option for TBI is that TBI can be associated with a loss of neurons, both at the site of the injury and sites distal to the injury. In the latter case, the neuronal loss is often the result of counter-coup forces and/or Wallerian degeneration.…”

“…These include pharmacological, steroidal, anti-inflammatory, cellular replacement, and behavioral methods. [1][2][3][4][5] Although a number of compounds have been tested in phase 3 clinical trials, none have proven to be efficacious at significantly improving outcomes. Advances in technology bring forth new treatment options that are being readily explored in experimental and clinical settings.…”