Neural Stem-Like Cells Derived from Human Amnion Tissue are Effective in Treating Traumatic Brain Injury in Rat

Abstract

Although human amnion derived mesenchymal stem cells (AMSC) are a promising source of stem cells, their therapeutic potential for traumatic brain injury (TBI) has not been widely investigated. In this study, we evaluated the therapeutic potential of AMSC using a rat TBI model. AMSC were isolated from human amniotic membrane and characterized by flow cytometry. After induction, AMSC differentiated in vitro into neural stem-like cells (AM-NSC) that expressed higher levels of the neural stem cell markers, nestin, sox2 and musashi, in comparison to undifferentiated AMSC. Interestingly, the neurotrophic factors, brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), neurotrophin 3 (NT-3), glial cell derived neurotrophic factor (GDNF) and ciliary neurotrophic factor (CNTF) were markedly upregulated after neural stem cell induction. Following transplantation in a rat TBI model, significant improvements in neurological function, brain tissue morphology, and higher levels of BDNF, NGF, NT-3, GDNF and CNTF, were observed in the AM-NSC group compared with the AMSC and Matrigel groups. However, few grafted cells survived with minimal differentiation into neural-like cells. Together, our results suggest that transplantation of AM-NSC promotes functional rehabilitation of rats with TBI, with enhanced expression of neurotrophic factors a likely mechanistic pathway.

Neurotrauma: The Crosstalk between Neurotrophins and Inflammation in the Acutely Injured Brain

“…NT-3 has been reported to promote post-traumatic neuroprotection, brain recovery, improvements in neurological functions, and attenuate neuronal injury [144,145,146,147,148,149]. In addition, NT-4 administration has been demonstrated to be neuroprotective in a wide variety of experimental TBI models, the NT-4 administration promotes an adaptive neuroprotective response in the injured brain [150,151,152,153,154,155].…”

Stem Cell Therapy in Brain Trauma: Implications for Repair and Regeneration of Injured Brain in Experimental TBI Models

“…Published data have reported that the use of human amnion-derived multipotent progenitor cells can significantly attenuate axonal degeneration and improve neurological function and brain tissue morphology of the injured rats (Chen et al, 2009;Yan et al, 2013). Intravenous administration of human adipose-derived stem cells or the derived culture medium into a controlled cortical impact rat model significantly improved motor and cognitive functions and reduced focal tissue damage and hippocampal cell loss (Tajiri et al, 2014).…”

Stem cell therapy for acute cerebral injury

“…Human fetal- and embryonic-derived NSCs have been shown to improve motor and cognitive function by producing neurotrophic factors, increasing angiogenesis and reducing astrogliosis. [39-44] Human blood, umbilical cord, placental and bone marrow progenitor, and mesenchymal stem cell transplantation in animal models of TBI has improved behavioral outcome. The production of neurotrophic factors could underlie this functional amelioration.…”