Survival and differentiation of neural progenitor cells derived from embryonic stem cells and transplanted into ischemic brain

Yasushi Takagi M.D., Ph.D. 1 , Masaki Nishimura M.D., Ph.D. 1 , Asuka Morizane M.D., Ph.D. 1 , Jun Takahashi M.D., Ph.D. 1 , Kazuhiko Nozaki M.D., Ph.D. 1 , Junya Hayashi M.D. 1 and Nobuo Hashimoto M.D., Ph.D. 1
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  • 1 Department of Neurosurgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
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Object. Cell replacement therapy including the use of embryonic stem cells (ESCs) may represent a novel treatment for damage from stroke. In this study, the authors transplanted neural progenitor cells (NPCs) derived from ESCs into ischemic brain and analyzed their survival and differentiation.

Methods. Multipotential NPCs were generated from ESCs by using the stromal cell—derived inducing activity method. These cells could differentiate in vitro into neurons, glia, and oligodendrocytes, thus revealing them to be neural stem cells. The NPCs were then transplanted into ischemic brain. At 2 weeks postischemia, the transplanted cells occupied 18.8 ± 2.5% of the hemispheric area; by 4 weeks postischemia, 26.5 ± 4% of the hemisphere. At 4 weeks after transplantation, green fluorescent protein (GFP)—positive transplanted cells showed mature neuronal morphological features. The authors also investigated the expression of differentiation markers and various neurotransmitters. Transplanted cells were immunopositive for neuronal nuclei, β-tubulin-III, and glial fibrillary acidic protein. Of the GFP-positive cells, 33.3 ± 11.5% were positive for glutamate decarboxylase, 13.3 ± 5.8% for glutamate, 2.1 ± 2.5% for tyrosine hydroxylase, 1.8 ± 2% for serotonin, and 0.4 ± 0.2% for choline acetyltransferase.

Conclusions. The authors confirmed the survival and differentiation of ESC-derived NPCs transplanted into the ischemic brain. Surviving transplanted cells expressed several neural markers and neurotransmitters. These findings indicate that these cells can function in the brain.

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Contributor Notes

Address reprint requests to: Yasushi Takagi, M.D., Ph.D., Department of Neurosurgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo, Kyoto 606–8507, Japan. email: ytakagi@kuhp.kyoto-u.ac.jp.
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