A therapeutic study of stem cell transplantation in rat stroke model
- Affiliations
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- 1Animal Model Research Group, Korea Institute of Toxicology, Daejeon, Korea
Abstract
- Background
Stem cell therapy is an advanced method of regenerative medicine that replace damaged stem cells to recover ir-reversible damaged tissues. Especially, the therapeutic strategy has been noticed in a field of neurological disease such as brain injury. Here, we performed in vivo study to investigate engraftment rate and efficacy of neural stem cells (NSCs) in rat stroke model.
Methods
The subcortical capsular infarct (SCI) with persistent motor impairment was induced by internal capsule destruction by photothrombotic methods in rats (n=12). NSCs were cultured from rat fetal brain (TP 14), and lenti virus containing them was labeled with green fluorescent protein (GFP). Hyaluronic acid was also injected to improve the engraftment rate of NSCs. NSCs were injected to the infarction area about 7 days after capsular infarct. The Single Pellet Reaching Task (SPRT) and open field tests was conducted to assess the motor system improvement. H&E staining and immunohistochemistry was performed to evaluate infarction measurement and engraftment rate.
Results
As a result, motor deficits and complete infarction of posterior limb of internal capsule were observed. In GFP staining, some of NSCs were successfully transplanted nearby infarction site and engraftment rate were also improved by co-treat-ment with 1% hyaluronic acid. In addition, we observed that some of injected NSC population differentiated into early stage of neurons (DCX+), oligodendrocytes (Olig2+), and astrocytes (GFAP+) in the penumbra, however most remained undifferentiated (Sox2+). SPRT score increased about 20% compared to pre-SCI modeling in two animals for 3–5 weeks after transplantation,
but no significant improvement in motor function was detected in other animals.
Conclusions
In this study, the possibility of recovery by NSCs injection was presented in SCI model. It is expected that successful engraftment of NSCs can be differentiated into functional cells, leading to an effective therapeutic strategy for patients
with stroke.