Transplanted human embryonic neural stem cells survive, migrate, differentiate and increase endogenous nestin expression in adult rat cortical peri‐infarction zone

Abstract

Transplantation of stem cells is a potential therapeutic strategy for stroke damage. The survival, migration, and differentiation of transplanted human embryonic neural stem cells in the acute post-ischemic environment were characterized and endogenous nestin expression after transplantation was investigated. Human embryonic neural stem cells obtained from the temporal lobe cortex were cultured and labeled with fluorescent 1,1'-dioctadecy-6,6'-di (4-sulfopheyl)-3,3,3',3'-tetramethylindocarbocyanin (DiI) in vitro. Labeled cells were transplanted into cortical peri-infarction zones of adult rats 24 h after permanent middle cerebral artery occlusion. Survival, migration, and differentiation of grafted cells were quantified in immunofluorescence-stained sections from rats sacrificed at 7, 14, and 28 days after transplantation. Endogenous nestin-positive cells in the cortical peri-infarction zone were counted at serial time points. The cells transplanted into the cortical peri-infarction zone displayed the morphology of living cells and became widely located around the ischemic area. Moreover, some of the transplanted cells expressed nestin, GFAP, or NeuN in the peri-infarction zone. Furthermore, compared with the control group, endogenous nestin-positive cells in the peri-infarction zone had increased significantly 7 days after cell transplantation. These results confirm the survival, migration, and differentiation of transplanted cells in the acute post-ischemic environment and enhanced endogenous nestin expression within a brief time window. These findings indicate that transplantation of neural stem cells into the peri-infarction zone may be performed as early as 24 h after ischemia.

Transplantation of <b><i>N</i></b>-Acetyl Aspartyl-Glutamate Synthetase-Activated Neural Stem Cells after Experimental Traumatic Brain Injury Significantly Improves Neurological Recovery

“…5A, images of cell death were detected with the TUNEL method. Transplantation of NSCs decreased cell death, compared to that observed in the model group, which was consistent with previous findings [1,27,28]. Notably, transplantation of NAAGS/NSCs suppressed cell death more significantly at 7 and 14 days after TBI, compared to NSC transplantation (Fig.…”

Influence of neural stem cell transplantation on angiogenesis in rats with spinal cord injury

“…Recent study has also shown that in a rat model of cerebral infarction, NSC transplantation not only provided a more favorable microenvironment for endogenous NSC proliferation and cell death inhibition through paracrine pathways, but also promoted angiogenesis (Zhang et al, 2011). This may be related to the release of various nutritional factors from NSCs, such as epidermal growth factor, fibroblast growth factor, and VEGF (Zhang et al, 2009). As a highly specific multifunctional cytokine that affects the vascular endothelium, VEGF functions in endothelial cell apoptosis inhibition, promotion of angiogenesis, and neuroprotection to promote the repair of spinal cord injury (Liu et al, 2010).…”

“…Neural stem cells (NSC) are promising candidate cells for neural transplantation therapy and have been shown to promote functional recovery after spinal cord injury through cell and tissue replacement (Sandner et al, 2012). Recent studies have shown that NSCs can not only replace damaged nerve tissue, but also promote angiogenesis in the ischemic area of cerebral infarction (Zhang et al, 2009). These cells can also promote the expression of various growth factors through paracrine signaling pathways (Ii et al, 2009).…”

Neural Stem Cells: Exogenous and Endogenous Promising Therapies for Stroke

“…In addition, this transplanted NSCs managed to survive, migrate, differentiate, and also induce improvement in neurological functions (Zhang et al, 2009a(Zhang et al, , 2009bZhang et al, 2010). Grafted NSCs enhanced the number of BrdU-positive cells in ischemic ipsilateral SVZ at 7 days after transplantation, an effect that persisted to at least 14 days post-transplantation.…”