Embryonic neural stem cells transplanted in middle cerebral artery occlusion model of rats demonstrated potent therapeutic effects, compared to adult neural stem cells

Abstract

Cell therapy using stem cells is awaited by stroke patients with impaired movement and cognitive functions, although intravenous alteplase-administration ameliorated outcomes of patients receiving the therapy within 3 h of onset. In this study, we explored the therapeutic effects of neural progenitor cells (NPC) upon middle cerebral artery occlusion (MCAO) model of rats with exploration of the differences between adult and embryonic NPCs in therapeutic effects. GFP-labeled adult or embryonic NPCs were transplanted for transient MCAO model of rats at 1h after reperfusion. Rats were examined behaviorally using limb placement test, rotarod test and cylinder test with neuroradiological assessment using magnetic resonance imaging (MRI). Consequently after euthanasia, rats were immunohistochemically investigated to explore graft survival and immune reaction. MRI of rats receiving NPCs revealed significant reduction of infarct volumes, compared to vehicle-treated rats with corresponding behavioral amelioration. The transplanted cells were surviving in rats receiving NPCs, although the number of embryonic NPCs was significantly higher than that of adult NPCs. Iba-1-positive inflammatory cells of rats receiving adult NPCs were prominent, compared to those receiving embryonic NPCs, which might be a rationale for the differences between rats receiving adult and embryonic NPCs in the number of surviving NPCs. On the contraries, adult NPCs surely demonstrated therapeutic effects with a few surviving cells, thus indicating that the therapeutic effects might be due to trophic/growth factor-secretion from transplanted NPCs, rather than replacement of damaged host neurons. Therapeutic effects of NPCs for MCAO model of rats were clarified in this study. Transplantation of NPCs will be a hopeful strategy for stroke patients, although further studies are required for the patient safety and underlying mechanisms.

Combination effect ofp-hydroxybenzyl alcohol and mesenchymal stem cells on the recovery of brain damage in a rat model of brain ischemia

“…Stem cell transplantation has the potential to provide protection and regeneration after ischemic injury (Kelly et al 2004;Takahashi et al 2008). Many studies showed that the administration of NPCs and MSCs via different routes of delivery after experimental stroke reduced the infarct volume and improved functional recovery (Bliss et al 2007).…”

Transplantation of telencephalic neural progenitors induced from embryonic stem cells into subacute phase of focal cerebral ischemia

“…Some transplantation protocols apply to the early phase of ischemia, 8 or through the use of hematopoietic progenitor cells can depend on the trophic or growth factor secretion to reduce ischemic injury. 25 Our original purpose is to achieve functional recovery by cell replacement at the chronic stage.…”

“…4 In comparison, several stem-cell-based transplantation studies for cerebral ischemia have demonstrated safety and functional recovery. [5][6][7][8][9] Transplanted stem cells have been isolated from various sources, such as blastocysts, fetal and adult CNS, bone marrow, and umbilical cord. Among them, embryonic stem (ES) cells are self-renewing, pluripotent cells derived from the inner cell mass of the pre-implantation blastocyst.…”

“…10 Embryonic neural progenitors survive longer than adult neural progenitors, with less inflammation. 8 Buhnemann et al 11 showed that transplanted ES cells demonstrate characteristics of electrophysiologically functional neurons with voltage-gated sodium currents. We previously reported that transplanted monkey and mouse ES cells could survive and differentiate into various types of neurons and glial cells, and reconstruct the neuronal network in mouse basal ganglia after middle cerebral artery (MCA) occlusion.…”

The neuroprotective and neurorescue effects of carbamylated erythropoietin Fc fusion protein (CEPO-Fc) in a rat model of Parkinson’s disease

“…Thereafter, the data were presented as percentages of the longest time on the rota-rod of three trials relative to the baseline (Takahashi et al, 2008).…”